The three steps  could be telescoped into a one-pot process.The method proved to be highly efficient and tolerated a wide rangeof substituents.A modular synthesisof highly substituted 3-azapyrroles has beendeveloped using a three-step sequence comprising copper-catalyzedalkyne–azide cycloaddition (CuAAC), N–H bond insertion,and cyclodehydration. 1-Sulfonyl-1,2,3-triazoles (1-STs) can be accessedfrom common alkyne and sulfonyl azide building blocks by CuAAC usingCuTC. Rhodium(II)-acetate-promoted 1-ST denitrogenation results inhighly electrophilic rhodium azavinyl carbenes that, here, underwentinsertion into the N–H bond of secondary α-aminoketonesto form 1,2-aminoalkenes. These products were cyclized and dehydratedusing BF The majority of examplesof this strategy involve triazoles and rhodium(II) carboxylate catalysts,although, recently, palladium(0) catalysts have shown analogous reactivitywith 1-trifluoromethanesulfonylbenzotriazoles 5.11The reactivity of 1-sulfonyl-1,2,3-triazoles 6 carboxylate, 1-STs formed an electron-deficientmetallocarbene 28 andthis formation of C–N bonds from N–H bonds is anotherclass of transformation that has been demonstrated with 1-STs.29 Here, we recognized that α-aminoketones are the hydrated equivalentof azirenes. Therefore, bringing together an α-aminoketone 16 and a 1-ST through N–H bond insertion (17) and then performing cyclodehydration would result in a strategicallycomplementary approach to valuable 3-azapyrroles 18.The insertion of metallocarbenes into X–Hbonds has beendeveloped into a valuable reaction,16 were formed by simple SN2 displacement of commercialα-haloketones 20 by anilines 19. Additionalsubstitution could be introduced to the α-position of the ketoneowing to its acidic nature (16g). The 1-STs 4 were formed in excellent yield by copper-catalyzed azide–alkynecycloaddition (CuAAC), and the modular nature of 1-ST synthesis isa key strength to this methodology. It is noteworthy that the useof copper(I) thiophene-2-carboxylate (CuTC) has been specificallydeveloped for 1-ST synthesis.9The substrates for this study, namely, α-aminoketones and1-STs are both readily accessed from readily available materials 3. The α-4a was treated with a slight excess of α-aminoketone 16a and 5 mol % of Rh2(OAc)4 in toluene at 80°C with 4 Å molecular sieves.30 These conditions resulted in the formation of the N–H insertionproduct 17a in high yield .31 Commonly employed Rh2(octanoate)4 and Rh2(esp)232 also promoted the N–H bond insertion but with lower efficiency,whereas no reaction occurred with bulky catalysts Rh2(triphenylacetate)4 and Rh2(S-tPTTL)433 (entries 4 and 5). The choiceof solvent had a minor effect on the reaction outcome, but the yieldwas improved to 93% when using toluene (entries 6–8). Increasingthe temperature from 60 to 80 °C provided a small increase inyield (entry 9), but increasing the temperature further caused theyield to decrease (entries 10 and 11); no reaction occurred below60 °C (entry 12). These findings were congruous with previouswork that showed Rh2(OAc)4 and Rh2(octanoate)4 to be the most effective for related N–Hbond insertions of α-amino esters, carbamates, and carbazoles.29 However, this process was more tolerant to solvent compared withother processes, specifically with toluene being generally incompatiblein the other examples.Next, the focus wasestablishing the optimum conditions for insertionof the metallocarbene derived from the 1-ST into the N–H bondof an appropriate aniline to bring together all the requisite atomsfor the planned pyrrole synthesis 1. A 4-to34 operation (It was anticipatedthat the Lewis acidic nature of the Rh(II) carboxylatemight also promote cyclodehydration of the 1,2-diaminoalkene to formthe corresponding pyrrole, but this transformation was not detected.Therefore, the heterocycle forming process was evaluated in a separateperation 2.17a with a selectionof dehydrating/acidic reagents; including p-toluenesulfonic acid, trimethylsilyl triflate, acetic acid, and phosphorusoxychloride resulted in the decomposition of substrate with only aminimal amount of the desired pyrrole 18a. Gratifyingly,using BF3·OEt235 (0.5 equiv) in dichloromethane at 80 °C gave a modest 49% yieldof pyrrole 18a (1H NMR). Increasing the amount of Lewis acid from 0.5 to 3.0 equivwas accompanied by an increase in yield to 72% (entries 2 and 3).1,2-Dichloroethane, toluene, and acetonitrile were considered as alternativesolvents, but the yields were lower than those of dichloromethane,giving complex mixtures (entries 4–6). Reducing the temperatureto less than 80 °C resulted in a more sluggish reaction (entries7 and 8).Treatment of the 1,2-diaminoalkene N-arylsubstituent, the Rh(II)-catalyzed N–H insertion and BF3·OEt2 promoted cyclodehydration were foundto be highly tolerant with good to excellent yields obtained for bothreactions (17a–d and 18a–d). Surprisingly, when a mesityl group or naphthylgroup was used, the Rh(II)-catalyzed reaction led to the pyrroles 18e,f in good yield directly, and no 1,2-diamineproduct 17e,f was observed. This differencein reactivity was attributed to promotion of the cyclization by raisingthe energy of unreactive conformations through steric interactions,placing the reacting centers in close proximity. Aliphatic amineswere challenging substrates for the Rh(II)-catalyzed reaction andso were not compatible with this process, presumably owing to theirincreased basicity.With the reaction conditions for a pyrrole synthesissequence established,the generality of this process was explored 4. Upon v18g in high yieldover the two operations.Variation of the ketone substituent was alsostudied, allowingcontrol of the 4- and 5-positions of the resulting pyrrole 5. Having18h,i). Interestingly, using more electron-withdrawingsubstituents NO2, CN, and Cl gave the expected N–Hinsertion products 17j–l alongsidethe corresponding pyrroles 18j–l,giving almost quantitative combined yields of the products. The twoproducts were readily separated by column chromatography, and the1,2-diaminoalkenes 17j–l could betransformed into their corresponding pyrroles 18j–l in good yield. Extending the reaction time in the presenceof rhodium catalyst to 16 h led to formation of only the pyrrole productsin high yield . It is suggested that direct formation ofpyrroles proceeded in these cases via the same products of N–Hinsertion, but that the more electron-withdrawing substituents activatedthe ketone toward nucleophilic attack, allowing cyclodehydration tooccur with the more mildly Lewis acidic Rh(II) catalyst. This is consistentwith the more electron-withdrawing NO2 and CN groups givingmore pyrrole product than the Cl substituent.When more conjugated or electron-rich ketone substituents werestudied, these also gave good yields for the two operations . Interestingly, the alkene substratecompleted N–H insertion (17o), despite the knownintramolecular rearrangement of alkenyl 1-STs to a different classof pyrrole.20 Pyrroles 18m,n were formed from these products using BF3·OEt2, again all with good to excellent yield. Variationof the sulfonyl group was also examined. Use of an electron-donating p-MeOC6H4SO2 group gavean excellent yield for N–H insertion (17p) buta moderate yield for cyclization to pyrrole 18p. On theother hand, the electron-withdrawing p-NO2C6H4SO2 group and the small mesylgroup gave a moderate yield for N–H insertion for 17q,r but an excellent yield for cyclodehydration to thepyrrole 18q,r.Different substituentsat the 4-position of 1-ST  studied 6. Hetero36 CuAAC is highly versatile and has been incorporated inone-pot sequences with rhodium(II) reactions of 1-STs since the earliestwork in the field,37 so this was also investigated here 4 were added to the mixture, and the vialwas sealed and heated for 3 h at 80 °C. Then BF3·OEt2 (3.0 equiv) was added, and the reaction mixture was stirredfor a further 15 min at 80 °C. Standard aqueous workup (NaHCO3) and filtration through silica gel afforded the pyrrole 18a in 90% yield. This represented a marked improvement overthe three separate steps (90 vs 58%) as well as making the overallprocess much more time- and material-efficient. Furthermore, the amountof copper and rhodium catalysts used was decreased to 5 and 1 mol%, respectively, without any deleterious effect. The one-pot processwas applied to a range of terminal alkynes 21, sulfonylazides 22, and amines 16, all of which gaveexcellent yields of the corresponding pyrroles 18 withconsiderable improvement over the stepwise equivalent. The one-potprocedure was also completed on a larger scale (4.61 mmol), using(CH2Cl)2 in place of CH2Cl2 and under reflux instead of in a sealed vial, and the protocol deliveredthe product 18h in excellent 76% yield.The key contributors to inefficiency in synthesisoften come notfrom the reactions themselves but in the purification of intermediates,so combining or telescoping multiple operations in one pot or dominosequences is an excellent way to boost efficiency.ted here 7. AlthouN-sulfonyl bond wasdemonstrated  acetate was the optimum catalystto promote 1-ST denitrogenation and insertion into the N–Hbond of a range of α-aminoketones to form 1,2-aminoalkenes inhigh yields. For bulky arylamines and electron-deficient ketones,the 1,2-aminoalkenes cyclized into the corresponding 3-azapyrrolesunder rhodium catalysis, but for most examples, this was not the caseand BFCAUTION: Nitrogen-rich compounds, suchas azides andtriazoles, can decompose violently with the loss of nitrogen gas.Although no problems were encountered in this study, appropriate precautionsshould be taken.1H and 13C signals of the solvents. 13C NMR spectra were collected with complete proton decoupling, andassignments were made using COSY, HSQC, HMBC, and NOESY experiments.Samples were melted directly from the procedures described. High-resolutionmass spectra were obtained on Agilent 6546 LC/Q-TOF and Bruker microTOFqinstruments by Analytical Services at the University of Glasgow Schoolof Chemistry. IR spectra were recorded using spectrometers fittedwith an ATR device. CH2Cl2 and toluene werepurified on a PureSolv PM500, and other reagents were used as received.Reactions were monitored by thin layer chromatography (TLC) usingMerck TLC silica gel 60 F254 aluminum-foil baked plates. Compoundswere visualized by UV light at nanometer resolution or by stainingwith potassium permanganate. Column chromatography was performed usinga Teledyne ISCO Combiflash Rf+ system using Redisep Rf silica cartridges.NMR spectra were recordedon 400 and 500 MHz Bruker spectrometers. Chemical shifts are givenin parts per million, and the spectra are calibrated to the residual 21 (1.1 equiv) were dissolved inPhMe (0.1 M) and cooled to 0 °C (ice bath). After 10 min, sulfonylazide 22 (1.0 equiv) was added in one portion and thereaction mixture was allowed to reach ambient temperature. When thereaction was complete , the mixture was dilutedwith saturated aqueous NH4Cl and extracted with ethyl acetate(3 × 10 mL mmol–1). The combined organic layerswere washed with brine, dried (MgSO4), filtered, and concentratedin vacuo. The residue was purified by flash column chromatography to give the 1-ST 4.Copper(I) thiophene-2-carboxylate(10 mol %) and alkyne 4a  as a whitesolid: mp 127 °C dec (lit. 158–159 °C);39 νmax (film) 3150, 2940, 1593,1497, 1392, 1194, and 1179 cm–1; 1H NMR δ 8.26 , 8.02 , 7.71 , 7.39 , 7.23 , 2.45  and 2.38 ; 13C{1H} NMR  δ147.4 (Ar), 147.3 (triazole C4), 139.1 (Ar), 133.2 (Ar), 130.4 (2× ArH), 129.7 (2 × ArH), 128.7 (2 × ArH), 126.0 (Ar),126.0 (2 × ArH), 118.5 (triazole C5), 21.8 (CH3) and21.3 (CH3); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C16H15N3NaO2S+ 336.0777; found 336.0767. Recordeddata are consistent with previous values.394-Ethynyltoluene  and 4-toluenesulfonylazide  were treated with CuTC  in PhMe (40 mL) according to General Procedure1 to give the title compound 4m  as a whitesolid: mp 87 °C dec (lit. 140–141 °C);18f νmax (film) 3136, 2924, 1593,1393, 1346, 1196, 1177, and 1092 cm–1; 1H NMR  δ 8.20 , 8.02 , 7.44, 7.39 , 7.34 , 7.08  and 2.45 ; 13C{1H} NMR  δ 147.4 (triazole C4), 142.5 (thiophene C2), 133.0 (Ar),130.8 (Ar), 130.5 (2 × ArH), 128.7 (2 × ArH), 127.8 (thiopheneCH), 126.3 (thiophene CH), 125.6 (thiophene CH), 118.1 (triazole C5)and 21.8 (CH3); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C13H11N3NaO2S2+ 328.0185; found328.0184. Recorded data are consistent with previous values.18f2-Ethynylthiophene  and 4-toluenesulfonylazide  were treated with CuTC  in PhMe (42 mL) according to General Procedure1 to give the title compound 4n  as a white solid: mp 96 °C dec (lit. 100–101 °C);40 νmax (film) 3144, 2932, 2839,1616, 1497, 1393, 1331, 1250, 1177, and 1088 cm–1; 1H NMR  δ8.22 , 8.01 , 7.74 , 7.37 , 6.95 , 3.83  and 2.43 ; 13C{1H} NMR  δ 160.2 (Ar), 147.3 (Ar), 147.2 (triazoleC4), 133.1 (Ar), 130.4 (2 × ArH), 128.6 (2 × ArH), 127.4(2 × ArH), 121.4 (Ar), 117.9 (triazole C5), 114.4 (2 × ArH),55.3 (OCH3) and 21.8 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C16H16N3O3S+ 330.0907;found 330.0909. Recorded data are consistent with previous values.401-Ethynyl-4-methoxybenzene and 4-toluenesulfonyl azide  were treatedwith CuTC  in PhMe (40 mL) according toGeneral Procedure 1 to give the title compound 4o  as a white solid: mp 100 °C dec (lit. 102–103°C);39 νmax (film)3148, 2928, 2859, 1593, 1389, 1177, and 1092 cm–1; 1H NMR  δ7.97 , 7.88 , 7.36 , 6.66 , 2.43 , 2.34–2.27, 2.22–2.15 , 1.78–1.71  and 1.70–1.61; 13C{1H} NMR  δ 148.9 (triazole C4), 147.0(Ar), 133.3 (Ar), 130.3 (2 × ArH), 128.5 (2 × ArH), 127.7(=CH), 125.8 (=C), 117.3 (triazole C5), 26.2 (CH2), 25.3(CH2), 22.2 (CH2), 22.0 (CH2) and21.8 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C15H18N3O2S+ 304.1114; found 304.1113. Recordeddata are consistent with previous values.391-Ethynylcyclohex-1-ene  and4-toluenesulfonyl azide  were treatedwith CuTC  in PhMe (40 mL) according toGeneral Procedure 1 to give the title compound 4p as a white solid: mp 95 °C dec (lit. 120–122 °C dec.);41 νmax (film) 3140, 3028, 2924,1381, 1231, 1184, 1161, and 1038 cm–1; 1H NMR  δ 8.26 , 7.76 , 7.28, 3.56  and 2.41 ; 13C{1H}NMR  δ 147.6 (triazoleC4), 139.4 (Ar), 129.8 (2 × ArH), 126.1 (2 × ArH), 125.8(Ar), 118.4 (triazole C5), 42.7 (CH3) and 21.4 (CH3); HRMS (ESI-TOF) m/z [M+ H]+ calcd for C10H12N3O2S+ 238.0645; found 238.0646. Recorded dataare consistent with previous values.414-Ethynyltoluene  andmethanesulfonyl azide  were treated withCuTC  in PhMe (40 mL) according to GeneralProcedure 1 to give the title compound 4q  as a white solid: mp 106 °C dec; νmax (film) 3140, 3109, 1532, 1408, 1397, 1346, and 1188 cm–1; 1H NMR  δ 8.44 ,8.36 , 8.30 , 7.71 , 7.25  and 2.39 ; 13C{1H} NMR  δ 151.6 (Ar), 148.0 (triazole C4), 141.6 (Ar), 139.6 (Ar),130.1 (2 × ArH), 129.8 (2 × ArH), 126.1 (2 × ArH),125.4 (Ar), 125.0 (2 × ArH), 118.6 (triazole C5) and 21.4 (CH3); HRMS (ESI-TOF) m/z [M(hydrolyzedtriazole) + H]+ calcd for C9H10N3+ 160.0869; found 160.0875.4-Ethynyltoluene  and 4-nitrobenzenesulfonyl azide were treated with CuTC  in PhMe (40 mL)according to General Procedure 1 to give the title compound 4r  as a white solid: mp 102 °C dec; νmax (film) 2940, 2923, 1593, 1577, 1497, 1391, 1233, and 1168cm–1; 1H NMR  δ 8.26 , 8.08 , 7.71 , 7.24 , 7.03 , 3.89  and 2.38 ; 13C{1H}NMR  δ 12707.0 (Ar),165.3 (Ar), 147.4 (triazole C4), 139.1 (Ar), 131.2 (2 × ArH),129.7 (2 × ArH), 127.9 (Ar), 126.0 (2 × ArH), 118.4 (triazoleC5), 115.1 (2 × ArH), 55.9 (OCH3) and 21.3 (CH3); HRMS (ESI-TOF) m/z [M+ Na]+ calcd for C16H15N3NaO3S+ 352.0726; found 352.0719. Recorded dataare consistent with previous values.424-Ethynyltoluene  and 4-methoxybenzenesulfonyl azide were treated with CuTC  in PhMe (20 mL)according to General Procedure 1 to give the title compound 19 (1.0 equiv) was dissolved in a 1:1 mixtureof water and ethanol (0.2 M). NaHCO3 (1.0 equiv) was addedfollowed by the α-bromoketone 20 (1.0 equiv), andthe reaction mixture was stirred until completion . The reaction mixture was diluted with ethyl acetate, and the aqueousphase was extracted with ethyl acetate (3 × 5 mL mmol–1). The combined organic layers were washed with brine, dried (MgSO4), and concentrated in vacuo. This product was either purifiedby recrystallization from CHCl3/pentane or by column chromatography.Amine p-Toluidine  and2-bromo-4′-methylacetophenone were treated with sodium hydrogen carbonate  in ethanol (30 mL) and water (30 mL) according to General Procedure2 for 16 h, and then the crude product was purified by recrystallization(CHCl3/pentane) to give the title compound 16a  as a yellow solid: mp 130–138 °C (lit.130–133 °C);43 νmax (film) 3405, 3029, 1682, 1612, 1527, and 1356 cm–1; 1H NMR  δ7.92 , 7.31 , 7.04 , 6.65 , 4.85 , 4.58 , 2.44  and 2.26 ; 13C{1H}NMR  δ 194.9 (C=O),144.9 (Ar), 144.8 (Ar), 132.5 (Ar), 129.8 (2 × ArH), 129.5 (2× ArH), 127.8 (2 × ArH), 127.0 (Ar), 113.2 (2 × ArH),50.6 (CH2), 21.8 (CH3) and 20.4 (CH3); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C16H17NNaO+ 262.1202;found 262.1204.3/pentane) to give the titlecompound 16b  as a white solid: mp 125 °Cdec (lit. 167–169 °C);44 νmax (film) 3393, 3030, 1675, 1603, 1499, 1353, 1188, and 1092cm–1; 1H NMR  δ 7.90 , 7.31 , 7.16 , 6.64 , 4.54  and 2.44 ; 13C{1H} NMR  δ 194.2 (C=O), 145.6 (Ar), 145.0 (Ar), 132.2(Ar), 129.6 (2 × ArH), 129.2 (2 × ArH), 127.8 (2 ×ArH), 122.4 (Ar), 114.1 (2 × ArH), 50.1 (CH2) and21.7 (CH3); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C15H14ClNNaO+ 282.0656; found 282.0655.4-Chloroaniline  and 2-bromo-4′-methylacetophenone were treated with sodium hydrogen carbonate in ethanol (5 mL) and water (5 mL) accordingto General Procedure 2 for 24 h, and then the crude product was purifiedby recrystallization (CHCl3/pentane) to give the title compound 16c  as a white solid: mp 133–135 °C; νmax (film) 3402, 2928, 1678, 1605, 1501, 1362, 1339, 1254,1161, and 1115 cm–1; 1H NMR  δ 7.94 , 7.33 , 7.32–7.29, 7.01–6.96 , 6.90–6.84 , 5.22 , 4.60  and 2.45; 13C{1H} NMR  δ 193.9 (C=O), 147.2(Ar), 145.1 (Ar), 132.2 (Ar), 131.7 , 129.7 (ArH), 129.6 (2 × ArH), 127.9 (2 × ArH),124.3 , 116.3 (ArH),114.1 , 108.7 , 49.7 (CH2) and 21.8 (CH3);HRMS (ESI-TOF) m/z [M + H]+ calcd for C16H15F3NO+ 294.1100; found 294.1110.3-Trifluoromethylaniline  and 2-bromo-4′-methylacetophenone  were treated with sodium hydrogen carbonate  in ethanol (5 mL) and water (5 mL) according to GeneralProcedure 2 for 16 h, and then the crude product was purified by recrystallizationand 2-bromo-4′-methylacetophenone were treated with sodium hydrogen carbonate  in ethanol (5 mL) and water (5 mL) according to General Procedure2 for 24 h, and then the crude product was purified by recrystallization(CHCl3/pentane) to give the title compound 16d  as a yellow solid: mp 97–100 °C (lit.102–103 °C);43 νmax (film) 3395, 3007, 2930, 2832, 1675, 1607, 1515, 1236,1182, and 1037 cm–1; 1H NMR  δ 7.91 , 7.31 , 6.83, 6.68 , 4.55 , 3.76  and 2.44 ; 13C{1H} NMR  δ 195.0 (C=O),152.3 (Ar), 144.7 (Ar), 141.6 (Ar), 132.5 (Ar), 129.5 (2 × ArH),127.8 (2 × ArH), 115.0 (2 × ArH), 114.2 (2 × ArH),55.8 (OCH3), 51.1 (CH2) and 21.7 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C16H18NO2+ 256.1332; found 256.1330.3/pentane) to give the title compound 16e  as an off white solid: mp 123 °C dec; νmax (film) 3028, 2974, 2924, 2870, 1686, 1609, and 1069 cm–1; 1H NMR  δ 7.84 ,7.27 , 6.84 ,4.54 , 4.48 , 2.42 , 2.35  and 2.24 ; 13C{1H} NMR  δ 196.4 (C=O), 144.6(Ar), 143.9 (Ar), 132.5 (Ar), 131.1 (Ar), 129.5 (2 × ArH), 129.4(2 × ArH), 129.0 (2 × Ar), 127.7 (2 × ArH), 55.3 (CH2), 21.7 (CH3), 20.5 (CH3) and 18.7 (2× CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C18H22NO+ 268.1696; found 268.1696.2,4,6-Trimethylaniline  and 2-bromo-4′-methylacetophenone  were treated with sodium hydrogen carbonate  in ethanol (5 mL) and water (5 mL) according to GeneralProcedure 2 for 16 h, and then the crude product was purified by recrystallization(CHCl3/pentane) to give the titlecompound 16f  as a gray solid: mp 120–125°C; νmax (film) 3418, 3051, 2920, 1686, 1582,1523, 1408, and 1235 cm–1; 1H NMR  δ 8.09–8.04 , 7.99 , 7.84–7.79, 7.54–7.46 , 7.38, 7.34 , 7.29–7.26 , 6.61 , 5.83 , 4.73  and 2.46; 13C{1H} NMR  δ 194.6 (C=O), 145.0(naphthyl C), 142.4 (Ar), 134.4 (naphthyl C), 132.5 (naphthyl C),129.7 (2 × ArH), 128.6 (naphthyl CH), 128.0 (2 × ArH), 126.5(naphthyl CH), 126.0 (naphthyl CH), 124.9 (naphthyl CH), 123.4 (Ar),120.3 (naphthyl CH), 117.7 (naphthyl CH), 104.4 (naphthyl CH), 50.2(CH2) and 21.8 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C19H18NO+ 276.1383; found 276.1389.2-Naphthylamine  and 2-bromo-4′-methylacetophenone were treated with sodium hydrogen carbonate in ethanol (5 mL) and water (5 mL) accordingto General Procedure 2 for 16 h, and then the crude product was purifiedby recrystallization  was added in three portions. The reaction wasstirred for 30 min and then MeI was added, and the reaction stirred for a further 3 h. Water was added,and the aqueous phase was extracted with Et2O (3 ×15 mL). The combined organic layers were washed with water, brine,dried over MgSO4, filtered, and concentrated in vacuo.Purification by flash column chromatography  gave the title compoundas an orange oil . Recorded data are consistent withprevious values:45 νmax (film) 3387, 2982, 2920, 1682, 1609, and 1520 cm–1; 1H NMR  δ7.92 , 7.30 , 6.98 , 6.60 , 5.08 , 2.43 ,2.23  and 1.46 ; 13C{1H} NMR  δ 200.5 (C=O), 144.5(Ar), 144.3 (Ar), 132.2 (Ar), 129.8 (2 × ArH), 129.5 (2 ×ArH), 128.6 (2 × ArH), 127.1 (Ar), 113.7 (2 × ArH), 53.6(CH), 21.7 (CH3), 20.4 (CH3) and 19.7 (CH3); HRMS (ESI-TOF) m/z [M+ H]+ calcd for C17H20NO+ 254.1539; found 254.1542.NaH was suspended in DMF (10 mL) and cooled to 0 °C (ice bath), and1-(4-tolyl)-2-(4-tolylamino)ethan-1-one p-Toluidine and 2-bromo-1-ethan-1-one  were treated with sodium hydrogen carbonate  in ethanol (10 mL) and water (10 mL) according to GeneralProcedure 2 for 2 h, and then the crude product was purified by recrystallization(CHCl3/pentane) to give the title compound 16h  as a yellow solid: mp 130 °C dec; νmax (film) 3395, 2970, 2924, 2862, 1682, 1620, 1528, 1057,and 1015 cm–1; 1H NMR  δ 8.55 , 8.07, 8.01 , 7.95 , 7.91 , 7.64 , 7.59 , 7.07 , 6.72 , 5.05, 4.76  and 2.27 ; 13C{1H} NMR  δ 195.2 (C=O), 144.8 (naphthyl C),135.9 (Ar), 132.5 (naphthyl C), 132.3 (naphthyl C), 129.9 (2 ×ArH), 129.6 (naphthyl CH), 129.4 (naphthyl CH), 128.8 (naphthyl CH),128.8 (naphthyl CH), 127.9 (naphthyl CH), 127.2 (Ar), 127.1 (naphthylCH), 123.4 (naphthyl CH), 113.3 (2 × ArH), 50.9 (CH2) and 20.4 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C19H18NO+ 276.1383; found 276.1391.p-Toluidine and 2-bromo-4′-methoxyacetophenone were treated with sodium hydrogen carbonate  in ethanol (10 mL) and water (10 mL) according to General Procedure2 for 2 h to give the title compound 16i as a brown solid: mp 111–114 °C; νmax (film) 3402, 3001, 2920, 2843, 1674, 1601, 1512, 1258, 1177, and1034 cm–1; 1H NMR  δ 8.00 , 7.04 , 6.98 , 6.66 , 5.00 , 4.56 , 3.90 and 2.26 ; 13C{1H} NMR  δ 193.6 (C=O), 164.0 (Ar), 144.9 (Ar), 130.1 (2 ×ArH), 129.9 (2 × ArH), 128.0 (Ar), 127.1 (Ar), 114.0 (2 ×ArH), 113.3 (2 × ArH), 55.5 (OCH3), 50.4 (CH2) and 20.4 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C16H18NO2+ 256.1332; found 256.1333.p-Toluidine and 2-bromo-4′-nitroacetophenone were treated with sodium hydrogen carbonate  in ethanol (10 mL) and water (10 mL) according to General Procedure2 for 2 h, and then the crude product was purified by recrystallization(CHCl3/pentane) to give the title compound 16j  as a red solid: mp 127 °C dec (lit. 147–150°C);46 νmax (film)3032, 2924, 2866, 1678, 1601, 1524, and 1346 cm–1; 1H NMR  δ8.37 , 8.18 , 7.05 , 6.65 , 4.74 , 4.66  and 2.26 ; 13C{1H} NMR  δ 194.1 (C=O), 150.7 (Ar), 144.4 (Ar),139.4 (Ar), 130.0 (2 × ArH), 128.9 (2 × ArH), 127.6 (Ar),124.1 (2 × ArH), 113.2 (2 × ArH), 51.4 (CH2)and 20.4 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C15H15N2O3+ 271.1077; found 271.1084.p-Toluidine and 2-bromo-4′-cyanoacetophenone were treated with sodium hydrogen carbonate  in ethanol (10 mL) and water (10 mL) according to General Procedure2 for 2 h to give the title compound 16k as an orange solid: mp 126 °C dec; νmax (film)3322, 2924, 2866, 2230, 1678, 1605, 1516, 1404, and 1277 cm–1; 1H NMR  δ8.11 , 7.83 , 7.04 , 6.64 , 4.62  and 2.26 ; 13C{1H} NMR  δ194.3 (C=O), 144.4 (Ar), 137.9 (Ar), 132.7 (2 × ArH),129.9 (2 × ArH), 128.2 (2 × ArH), 127.5 (Ar), 117.7 (Ar),117.1 (C≡N), 113.2 (2 × ArH), 51.2 (CH2) and20.4 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C16H15N2O+ 251.1179; found 251.1178.p-Toluidine and 2-bromo-4′-chloroacetophenone were treated with sodium hydrogen carbonate  in ethanol (10 mL) and water (10 mL) according to General Procedure2 for 2 h, and then the crude product was purified by recrystallization(CHCl3/pentane) to give the title compound 16l  as a yellow solid: mp 127–130 °C (lit.150–152 °C);44 νmax (film) 3391, 2916, 2859, 1682, 1589, and 1524 cm–1; 1H NMR  δ7.96 , 7.49 , 7.04 , 6.64 , 4.76 , 4.58  and 2.26 ; 13C{1H} NMR  δ 194.2 (C=O), 144.7 (Ar), 140.3 (Ar),133.3 (Ar), 129.9 (2 × ArH), 129.2 (2 × ArH), 129.2 (2 ×ArH), 127.2 (Ar), 113.2 (2 × ArH), 50.7 (CH2) and20.4 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C15H15ClNO+ 260.0837; found 260.0834.p-Toluidine  and2-bromo-1-cyclopropylethanone  were treatedwith sodium hydrogen carbonate  in ethanol(10 mL) and water (10 mL) according to General Procedure 2 for 16h to give the title compound 16u  as a brownsolid: mp 75–78 °C; νmax (film) 3395,3013, 2920, 2859, 1694, 1616, 1524, 1393, and 1069 cm–1; 1H NMR  δ7.01 , 6.54 , 4.52 , 4.15 , 2.24 , 2.01 , 1.16–1.12  and 1.01–0.95 ; 13C{1H} NMR  δ 206.5 (C=O), 144.8 (Ar), 129.8 (2× ArH), 126.9 (Ar), 113.0 (2 × ArH), 54.5 (CH2), 20.4 (CH3), 18.8 (cyclopropane CH) and 11.3 (2 ×cyclopropane CH2); HRMS (ESI-TOF) m/z [M + H]+ calcd for C12H16NO+ 190.1226; found 190.1230.p-Toluidine  and2-bromo-2′-methylacetophenone were treated with sodium hydrogen carbonate  in ethanol (10 mL) and water (10 mL) according to General Procedure2 for 16 h, and then the crude product was purified by recrystallization(CHCl3/pentane) to give the title compound 16v  as an orange solid: mp 124–127 °C; νmax (film) 3387, 2924, 2851, 1690, 1620, and 1524 cm–1; 1H NMR  δ7.74–7.71 , 7.46–7.42 , 7.34–7.29, 7.03 , 6.62, 4.48 , 2.55  and 2.25 ; 13C{1H} NMR  δ 198.8 (C=O), 144.9 (Ar), 138.9 (Ar), 135.4(Ar), 132.3 (ArH), 132.1 (ArH), 129.9 (2 × ArH), 128.1 (ArH),127.0 (Ar), 125.9 (ArH), 113.2 (2 × ArH), 52.6 (CH2), 21.4 (CH3) and 20.4 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C16H18NO+ 240.1383; found 240.1388.2(OAc)4 (5 mol %) was addedto a solution of α-aminoketone 16 (1.1 equiv) andtriazole 4 (1.0 equiv) in toluene (0.03 M) in a flame-driedvial with freshly dried 4 Å molecular sieves. The vial was sealedwith a Teflon cap and stirred at 80 °C (heating block) untilcomplete . The reaction mixture was concentratedin vacuo and purified by flash column chromatography  to give the1,2-diamine product 17.Under argon, Rh4a  and α-aminoketone 16a  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3 to give the title compound 17a as a yellow solid: mp 61–69 °C; νmax (film)3250, 3032, 2924, 1690, 1609, 1512, and 1161 cm–1; 1H NMR  δ9.36 , 7.87 , 7.65 , 7.30 , 7.17 , 7.12 , 7.10 , 6.92, 6.75 , 6.30 , 4.66 , 2.45 , 2.34 , 2.33  and2.20 ; 13C{1H} NMR  δ 197.2 (C=O), 145.3(Ar), 143.3 (Ar), 143.0 (Ar), 137.9 (Ar), 137.4 (Ar), 132.7 (Ar),131.8 (Ar), 129.7 (2 × ArH), 129.6 (2 × ArH), 129.5 (2 ×ArH), 129.4 (2 × ArH), 128.3 (2 × ArH), 127.1 (Ar), 126.6(2 × ArH), 125.9 (=C), 124.9 (2 × ArH), 121.8 (=CH), 112.2(2 × ArH), 56.5 (CH2), 21.8 (CH3), 21.4(CH3), 21.1 (CH3) and 20.3 (CH3);HRMS (ESI-TOF) m/z [M + H]+ calcd for C32H33N2O3S+ 525.2206; found 525.2204.Triazole 4a  and α-aminoketone 16b  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3 to give the title compound 17b as a yellow solid: mp 72 °C dec; νmax (film)3264, 3063, 2924, 1686, 1605, 1493, 1339, 1289, 1161, and 1092 cm–1; 1H NMR  δ 9.40 ,7.89 , 7.64 , 7.32 , 7.18–7.12 , 6.94 , 6.84 , 6.30 , 4.68, 2.47 , 2.40  and 2.36 ; 13C{1H} NMR  δ196.8 (C=O), 145.7 (Ar), 144.5 (Ar), 143.4 (Ar), 138.1 (Ar),137.8 (Ar), 132.2 (Ar), 131.6 (Ar), 129.7 (2 × ArH), 129.6 (2× ArH), 129.5 (2 × ArH), 128.9 (2 × ArH), 128.4 (2× ArH), 126.5 (2 × ArH), 125.5 (=C), 124.8 (2 × ArH),123.0 (Ar), 122.1 (=CH), 113.5 (2 × ArH), 56.4 (OCH3), 21.8 (CH3), 21.5 (CH3) and 21.1 (CH3); HRMS (ESI-TOF) m/z [M+ H]+ calcd for C31H30ClN2O3S+ 545.1660; found 545.1655.Triazole 4a  and α-aminoketone 16c  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3 to give the title compound 17c as a white solid: mp 110 °C dec; νmax (film)3136, 3032, 2928, 1678, 1609, 1335, and 1165 cm–1; 1H NMR  δ9.40 , 7.86 , 7.65 , 7.31 , 7.15–7.10, 7.06 ,6.97 , 6.94 , 6.64–6.60 , 6.57 , 4.71 , 2.45 , 2.34  and 2.32 ; 13C{1H}NMR  δ 196.6 (C=O),146.2 (Ar), 145.8 (Ar), 143.4 (Ar), 137.8 (Ar), 137.7 (Ar), 131.8(Ar), 131.8 , 131.5 (Ar), 129.8(ArH), 129.8 (2 × ArH), 129.7 (2 × ArH), 129.6 (2 ×ArH), 128.4 (2 × ArH), 126.6 (2 × ArH), 124.7 (2 ×ArH), 124.5 (=C), 122.5 (=CH), 115.5 (ArH), 114.9 , 108.5 , 56.5(CH2), 21.9 (CH3), 21.4 (CH3) and21.1 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C32H30F3N2O3S+ 579.1924; found 579.1928.Triazole 4a  and α-aminoketone 16d  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3 to give the title compound 17d as a yellow solid: mp 45–50 °C; νmax (film)3252, 2924, 2855, 1690, 1609, 1512, 1250, 1161, and 1034 cm–1; 1H NMR  δ9.32 , 7.86 , 7.63 , 7.28 , 7.16 , 7.11 , 7.10 , 6.88 , 6.53 , 6.32 , 4.63 , 3.70, 2.44 , 2.33  and 2.33 ; 13C{1H} NMR  δ 197.4 (C=O),152.4 (Ar), 145.4 (Ar), 143.1 (Ar), 139.9 (Ar), 138.0 (Ar), 137.5(Ar), 132.8 (Ar), 131.9 (Ar), 129.6 (2 × ArH), 129.6 (2 ×ArH), 129.5 (2 × ArH), 128.3 (2 × ArH), 126.7 (2 ×ArH), 126.2 (=C), 124.9 (2 × ArH), 121.8 (=CH), 114.7 (2 ×ArH), 113.3 (2 × ArH), 56.8 (CH2), 55.6 (OCH3), 21.8 (CH3), 21.5 (CH3) and 21.1 (CH3); HRMS (ESI-TOF) m/z [M– H]− calcd for C32H31N2O4S– 539.2010; found 539.2017.Triazole 4a  and α-aminoketone 16g  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3 to give the title compound 17g as a yellow solid: mp 65 °C dec; νmax (film)3094, 3028, 2924, 1674, 1605, 1512, 1343, 1289, 1235, and 1157 cm–1; 1H NMR  δ 10.51 ,8.09 , 7.72 , 7.37 , 7.31 ,7.15 , 7.11, 7.04 , 6.70 , 6.25 , 5.48, 2.49 , 2.35, 2.28 , 2.13 and 1.11 ; 13C{1H} NMR  δ 203.3 (C=O), 145.5 (Ar), 143.2 (Ar), 143.0 (Ar),138.1 (Ar), 136.6 (Ar), 134.6 (Ar), 131.4 (Ar), 129.9 (2 × ArH),129.7 (2 × ArH), 129.5 (2 × ArH), 129.5 (2 × ArH),128.7 (2 × ArH), 126.9 (Ar), 126.7 (2 × ArH), 125.5 (=CH),123.9 (2 × ArH), 121.2 (=C), 112.3 (2 × ArH), 57.7 (CH),21.8 (CH3), 21.5 (CH3), 21.0 (CH3), 20.2 (CH3) and 16.0 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C33H35N2O3S+ 539.2363;found 539.2368.Triazole 4a  and α-aminoketone 16h  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3 to give the title compound 17h as a yellow solid: mp 58 °C dec; νmax (film)3240, 3032, 2920, 2862, 1678, 1512, 1161, and 1092 cm–1; 1H NMR  δ9.31 , 8.46 , 8.02 ,7.95 , 7.94 , 7.91 , 7.66 , 7.65–7.63 , 7.59 , 7.21 , 7.13 , 7.08 , 6.94, 6.77 , 6.34 , 4.81 , 2.34 , 2.26  and 2.20 ; 13C{1H} NMR  δ 197.6 (C=O), 143.3 (Ar), 143.1 (naphthylC), 138.0 (Ar), 137.5 (naphthyl C), 136.1 (naphthyl C), 132.8 (Ar),132.3 (Ar), 131.7 (Ar), 130.0 (naphthyl CH), 129.7 (2 × ArH),129.6 (2 × ArH), 129.6 (naphthyl CH), 129.4 (2 × ArH), 129.1(naphthyl CH), 128.8 (naphthyl CH), 127.9 (naphthyl CH), 127.3 (Ar),127.2 (naphthyl CH), 126.7 (2 × ArH), 125.9 (=C), 125.0 (2 ×ArH), 123.6 (naphthyl CH), 122.0 (=CH), 112.3 (2 × ArH), 56.8(CH2), 21.4 (CH3), 21.1 (CH3) and20.3 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C35H33N2O3S+ 561.2206; found 561.2208.Triazole 4a  and α-aminoketone 16i  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3 to give the title compound 17i as a brown solid: mp 69–74 °C; νmax (film)3225, 3028, 2920, 2859, 1674, 1597, 1512, 1339, 1265, 1234, 1161,and 1092 cm–1; 1H NMR  δ 9.45 , 7.95 ,7.63 , 7.16 , 7.12 , 7.10 , 6.95 , 6.90 , 6.74 ,6.29 , 4.62 , 3.89 , 2.34 , 2.32  and 2.19 ; 13C{1H} NMR  δ 196.0 (C=O), 164.4 (Ar), 143.4 (Ar), 143.0(Ar), 138.1 (Ar), 137.4 (Ar), 132.8 (Ar), 130.6 (2 × ArH), 129.7(2 × ArH), 129.6 (2 × ArH), 129.4 (2 × ArH), 127.4(Ar), 127.1 (Ar), 126.7 (2 × ArH), 125.9 (=C), 124.9 (2 ×ArH), 121.9 (=CH), 114.0 (2 × ArH), 112.2 (2 × ArH), 56.3(CH2), 55.6 (OCH3), 21.5 (CH3), 21.1(CH3) and 20.3 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C32H33N2O4S+ 541.2156;found 541.2158.Triazole 4a  and α-aminoketone 16j  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3 to give the title compound 17j as a pink solid. Under the reaction conditions, there was also somecyclodehydration to the corresponding pyrrole 18j : mp 115 °C dec; νmax (film) 3183, 2924,2856, 1694, 1516, 1343, 1215, 1161, and 1092 cm–1; 1H NMR  δ8.78 , 8.34 , 8.11 , 7.64 , 7.17 , 7.15 , 7.11 , 6.88, 6.76 , 6.28 , 4.71 , 2.37 , 2.33  and 2.21 ; 13C{1H} NMR  δ 196.5 (C=O), 150.9 (Ar), 143.3 (Ar), 143.0(Ar), 138.7 (Ar), 137.9 (Ar), 137.8 (Ar), 132.4 (Ar), 129.8 (2 ×ArH), 129.7 (2 × ArH), 129.5 (2 × ArH), 129.3 (2 ×ArH), 127.8 (Ar), 126.7 (2 × ArH), 125.4 (=C), 125.0 (2 ×ArH), 124.1 (2 × ArH), 121.6 (=CH), 112.3 (2 × ArH), 57.0(CH2), 21.5 (CH3), 21.1 (CH3) and20.3 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C31H30N3O5S+ 556.1901; found 556.1883.Triazole 4a  and α-aminoketone 16k  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3 to give the title compound 17k as a yellow solid. Under the reaction conditions, there was also somecyclodehydration to the corresponding pyrrole 18k : mp 113 °C dec; νmax (film) 3245, 3028,2924, 2856, 2230, 1690, 1512, 1161, and 1092 cm–1; 1H NMR  δ8.81 , 8.04 , 7.80 , 7.64 , 7.16 , 7.14 , 7.11 , 6.88, 6.75 , 6.27 , 4.68 , 2.37 , 2.33  and 2.20 ; 13C{1H} NMR  δ 196.7 (C=O), 143.2 (Ar), 143.0 (Ar), 137.9(Ar), 137.7 (Ar), 137.2 (Ar), 132.7 (2 × ArH), 132.4 (Ar), 129.8(2 × ArH), 129.7 (2 × ArH), 129.5 (2 × ArH), 128.6(2 × ArH), 127.8 (Ar), 126.7 (2 × ArH), 125.4 (=C), 125.0(2 × ArH), 121.6 (=CH), 117.6 (Ar), 117.5 (C≡N), 112.3(2 × ArH), 56.9 (CH2), 21.5 (CH3), 21.1(CH3) and 20.3 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C32H30N3O3S+ 536.2002;found 536.2005.Triazole 4a  and α-aminoketone 16l  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3 to give the title compound 17l as a yellow solid. Under the reaction conditions, there was also somecyclodehydration to the corresponding pyrrole 18l : mp 63 °C dec; νmax (film) 3175, 3028,2920, 1686, 1589, 1512, 1339, 1223, 1161, and 1092 cm–1; 1H NMR  δ9.09 , 7.89 , 7.63 , 7.47 , 7.15 , 7.12 , 7.10 , 6.90, 6.75 , 6.28 , 4.64 , 2.35 , 2.33  and 2.20 ; 13C{1H} NMR  δ 196.6 (C=O), 143.2 (Ar), 143.1 (Ar), 140.9(Ar), 137.9 (Ar), 137.6 (Ar), 132.6 (Ar), 132.6 (Ar), 129.7 (2 ×ArH), 129.6 (2 × ArH), 129.6 (2 × ArH), 129.4 (2 ×ArH), 129.2 (2 × ArH), 127.5 (Ar), 126.7 (2 × ArH), 125.7(=C), 124.9 (2 × ArH), 121.8 (=C), 112.2 (2 × ArH), 56.6(CH2), 21.5 (CH3), 21.1 (CH3) and20.3 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C31H30ClN2O3S+ 545.1660; found 545.1659.Triazole 4m  and α-aminoketone 16a  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3 to give the title compound 17m as an orange solid: mp 126 °C dec; νmax (film)3148, 3032, 2920, 1678, 1609, 1516, 1339, 1231, 1161, and 1092 cm–1; 1H NMR  δ 9.39 ,7.88 , 7.64 , 7.31 , 7.12 , 7.10 , 6.92 , 6.90 , 6.84 , 6.77 , 6.31, 4.71 , 2.45 , 2.33  and 2.19 ; 13C{1H}NMR  δ 197.2 (C=O),145.5 (Ar), 143.1 (Ar), 142.6 (thiophene C2), 141.0 (Ar), 137.8 (Ar),131.8 (Ar), 129.7 (2 × ArH), 129.6 (2 × ArH), 129.4 (2 ×ArH), 128.3 (2 × ArH), 127.7 (thiophene CH), 127.5 (Ar), 126.7(2 × ArH), 123.8 (thiophene CH), 122.9 (thiophene CH), 122.0(=CH), 121.7 (=C), 112.4 (2 × ArH), 56.5 (CH2), 21.8(CH3), 21.5 (CH3) and 20.3 (CH3);HRMS (ESI-TOF) m/z [M + H]+ calcd for C29H29N2O3S2+ 517.1614; found 517.1617.Triazole 4n  and α-aminoketone 16a  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3 to give the title compound 17n as an orange solid: mp 66–70 °C; νmax (film) 3275, 3032, 2924, 1682, 1601, 1512, 1339, 1250, and 1161cm–1; 1H NMR  δ 9.27 , 7.86 , 7.64 , 7.28 , 7.19 , 7.11, 6.82 , 6.81 ,6.74 , 6.29 , 4.63 , 3.79, 2.44 , 2.34  and 2.19 ; 13C{1H} NMR  δ197.2 (C=O), 159.3 (Ar), 145.3 (Ar), 143.3 (Ar), 143.0 (Ar),138.0 (Ar), 131.9 (Ar), 129.7 (2 × ArH), 129.5 (2 × ArH),129.4 (2 × ArH), 128.3 (2 × ArH), 128.1 (Ar), 127.2 (Ar),126.7 (2 × ArH), 126.3 (2 × ArH), 125.8 (=C), 120.8 (=CH),114.3 (2 × ArH), 112.3 (2 × ArH), 56.4 (CH2),55.4 (OCH3), 21.8 (CH3), 21.5 (CH3) and 20.3 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C32H33N2O4S+ 541.2156; found 541.2148.Triazole 4o  and α-aminoketone 16a  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3 to give the title compound 17o as a yellow solid: mp 140 °C dec; νmax (film)3152, 3032, 2924, 1678, 1609, 1516, 1343, and 1161 cm–1; 1H NMR  δ9.41 , 7.90 , 7.64 , 7.32 , 7.09 , 6.79 , 6.51 ,6.18 , 5.46 , 4.62 , 2.46, 2.31 , 2.19 , 2.15–2.08 , 2.07–2.00, 1.72–1.64  and 1.62–1.52 ; 13C{1H} NMR  δ 197.6(C=O), 145.3 (Ar), 143.3 (Ar), 142.9 (Ar), 137.8 (Ar), 132.0(Ar), 129.9 (=C), 129.6 (2 × ArH), 129.5 (2 × ArH), 129.3(2 × ArH), 128.4 (=C), 128.3 (2 × ArH), 126.6 (2 ×ArH), 126.5 (Ar), 123.5 (=CH), 121.3 (=CH), 111.7 (2 × ArH),57.2 (CH2), 25.5 (CH2), 24.9 (CH2), 22.5 (CH2), 22.2 (CH2), 21.8 (CH3), 21.4 (CH3) and 20.3 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C31H35N2O3S+ 515.2363;found 515.2355.Triazole 4r  and α-aminoketone 16a  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3 to give the title compound 17p as a yellow solid: mp 60–66 °C; νmax (film)3148, 3028, 2920, 1678, 1597, 1516, 1339, 1304, 1258, 1157, and 1092cm–1; 1H NMR  δ 9.31 , 7.86 , 7.69 , 7.28 , 7.16 , 7.10, 6.90 , 6.77 ,6.76 , 6.30 , 4.65 , 3.79, 2.44 , 2.32  and 2.19 ; 13C{1H} NMR  δ197.2 (C=O), 162.6 (Ar), 145.3 (Ar), 143.4 (Ar), 137.4 (Ar),132.8 (Ar), 132.7 (Ar), 131.9 (Ar), 129.7 (2 × ArH), 129.6 (2× ArH), 129.5 (2 × ArH), 128.8 (2 × ArH), 128.3 (2× ArH), 127.2 (Ar), 125.8 (=C), 124.9 (2 × ArH), 122.0 (=CH),113.9 (2 × ArH), 112.2 (2 × ArH), 56.5 (OCH3),55.4 (CH3), 21.8 (CH3), 21.1 (CH3) and 20.3 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C32H33N2O4S+ 541.2156; found 541.2158.Triazole 4q  and α-aminoketone 16a  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3 to give the title compound 17q as a yellow solid: mp 143 °C dec; νmax (film)3102, 3032, 2920, 1678, 1605, 1516, 1346, 1231, and 1165 cm–1; 1H NMR  δ9.77 , 8.12 , 7.88 , 7.85 , 7.29 , 7.18 , 7.12 , 6.88, 6.68 , 6.26 , 4.65 , 2.44 , 2.34  and 2.16 ; 13C{1H} NMR  δ 197.9 (C=O), 149.7 (Ar), 146.6 (Ar), 145.9(Ar), 143.7 (Ar), 138.2 (Ar), 132.1 (Ar), 131.5 (Ar), 129.7 (2 ×ArH), 129.7 (2 × ArH), 129.6 (2 × ArH), 128.3 (2 ×ArH), 128.0 (Ar), 127.9 (=C), 127.7 (2 × ArH), 125.2 (2 ×ArH), 124.0 (2 × ArH), 120.6 (=CH), 112.5 (2 × ArH), 56.6(CH2), 21.8 (CH3), 21.1 (CH3) and20.1 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C31H30N3O5S+ 556.1901; found 556.1903.Triazole 4p  and α-aminoketone 16a  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3 to give the title compound 17r as a yellow solid: mp 111–116 °C; νmax (film) 2924, 1682, 1609, 1516, 1331, 1231, and 1150 cm–1; 1H NMR  δ9.18 , 7.91 , 7.29 , 7.24 , 7.14 , 6.98 , 6.85 ,6.54 , 4.76 , 2.90 , 2.43 , 2.35  and 2.23 ; 13C{1H} NMR  δ 197.5 (C=O), 145.5 (Ar), 143.7 (Ar), 137.7(Ar), 132.6 (Ar), 131.8 (Ar), 130.0 (2 × ArH), 129.7 (2 ×ArH), 129.6 (2 × ArH), 128.3 (2 × ArH), 127.8 (Ar), 125.7(=C), 125.0 (2 × ArH), 121.4 (=CH), 112.6 (2 × ArH), 56.4(CH2), 42.0 (CH3), 21.8 (CH3), 21.1(CH3) and 20.3 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C26H29N2O3S+ 449.1893;found 449.1901.Triazole 17 (1.0 equiv) in CH2Cl2 (0.03 M) in a flame-dried vial. The vial wassealed with a Teflon cap and heated at 80 °C (heating block)for 15 min. The reaction mixture was cooled to ambient temperature;saturated aqueous NaHCO3 was added, and the aqueous phasewas extracted with CH2Cl2 (3 × 30 mL mmol–1). The combined organic layers were washed with brine,dried (MgSO4), and concentrated in vacuo. Purificationby column chromatography  gave the pyrrole 18.Under argon,boron trifluoride diethyl etherate (3.0 equiv) was added in one portionto a solution of 1,2-diamine 21 (1.1 equiv) in CH2Cl2 (0.03 M) in a flame-dried vial with freshly dried 4 Åmolecular sieves. The mixture was cooled to 0 °C (ice bath) andstirred for 10 min. Then sulfonyl azide 22 (1.1 equiv)was added, and the reaction mixture was allowed to reach ambient temperature.When the CuAAC reaction was complete , amine 16 (1.0 equiv) was added, followed by Rh2(OAc)4 (1 mol %), and the vial was sealed with a Teflon cap andheated to 80 °C (heating block) for 3 h. The reaction mixturewas cooled to ambient temperature and boron trifluoride diethyl etherate(3.0 equiv) was added in one portion. The vial was sealed and heatedto 80 °C (heating block) for 15 min. After being cooled to ambienttemperature, the reaction was quenched by addition of saturated aqueousNaHCO3, and the aqueous phase was extracted with CH2Cl2 (3 × 30 mL mmol–1).The combined organic layers were washed with brine, dried (MgSO4), filtered through a short pad of silica (eluting with CH2Cl2), and concentrated in vacuo to deliver thepyrrole 18.Underargon, copper(I) thiophene-2-carboxylate (5 mol %) was added to asolution of alkyne 17a was treated with BF3·OEt2  in CH2Cl2 (6.7 mL) accordingto General Procedure 4 to give the title compound 18a  as an orange solid. 4-Ethynyltoluene  and 4-toluenesulfonyl azide  were treated with CuTC  inCH2Cl2 (17 mL), followed by α-aminoketone 16a  and Rh2(OAc)4 , and finally BF3·OEt2  accordingto General Procedure 5 to give the title compound 18a : mp 170 °C dec; νmax (film)3268, 3028, 1516, 1389, 1327, and 1157 cm–1; 1H NMR  δ 7.35, 7.25 , 7.09 , 7.07, 6.97 , 6.94 , 6.88, 6.87 ,6.82 , 6.24 ,2.37 , 2.33 , 2.32 and 2.30 ; 13C{1H} NMR  δ142.3 (Ar), 137.4 (Ar), 137.0 (Ar), 136.7 (Ar), 136.4 (Ar), 135.5(Ar), 131.9 (Ar), 131.0 (Ar), 129.8 (2 × ArH), 129.5 (2 ×ArH), 129.0 (2 × ArH), 128.7 (2 × ArH), 128.6 (2 ×ArH), 127.4 (2 × ArH), 127.2 (pyrrole), 127.0 (2 × ArH),125.2 (2 × ArH), 123.6 (pyrrole), 119.3 (pyrrole CH), 115.3 (pyrrole),21.3 (CH3), 21.3 (CH3), 21.2 (CH3) and 21.2 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C32H31N2O2S+ 507.2101; found 507.2100.1,2-Diaminoalkene 17b  was treated with BF3·OEt2  in CH2Cl2 (6.7 mL) according to General Procedure 4 to give the titlecompound 18b  as a yellow solid. 4-Ethynyltoluene and 4-toluenesulfonyl azide  were treated with CuTC  in CH2Cl2 (10 mL), followed by α-aminoketone 16b  and Rh2(OAc)4 , and finally BF3·OEt2  accordingto General Procedure 5 to give the title compound 18b : mp 170 °C dec; νmax (film)3268, 3020, 2920, 1497, 1385, 1327, 1157, and 1092 cm–1; 1H NMR  δ7.31 , 7.22 , 7.21 , 7.07 , 6.99 , 6.94 , 6.85 , 6.84 , 6.81 , 6.19 , 2.35 , 2.31  and 2.28 ; 13C{1H} NMR  δ142.4 (Ar), 138.4 (Ar), 137.1 (Ar), 137.0 (Ar), 135.8 (Ar), 132.3(Ar), 130.7 (Ar), 129.9 (2 × ArH), 129.3 (Ar), 129.1 (2 ×ArH), 129.0 (2 × ArH), 128.9 (2 × ArH), 128.7 (2 ×ArH), 127.4 (2 × ArH), 127.0 (2 × ArH), 126.8 (pyrrole),126.5 (2 × ArH), 124.2 (pyrrole), 119.1 (pyrrole CH), 115.9 (pyrrole),21.4 (CH3), 21.3 (CH3) and 21.2 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C31H28ClN2O2S+ 527.1555; found 527.1562.1,2-Diaminoalkene 17c  was treated with BF3·OEt2  in CH2Cl2 (3.3 mL) according to General Procedure 4 to give the titlecompound 18c  as a yellow solid. 4-Ethynyltoluene and 4-toluenesulfonyl azide  were treated with CuTC  in CH2Cl2 (10 mL), followed by α-aminoketone 16c  and Rh2(OAc)4 , and finally BF3·OEt2  accordingto General Procedure 5 to give the title compound 18c : mp 145 °C dec; νmax (film)3256, 2924, 1497, 1458, 1385, 1327, 1161, 1130, 1096, and 1072 cm–1; 1H NMR  δ 7.48–7.43 , 7.40–7.37, 7.35 , 7.31, 7.23 , 7.17–7.13 , 7.07 , 6.95 , 6.91 , 6.84 , 6.82 , 6.20, 2.35 , 2.30  and 2.28 ; 13C{1H} NMR  δ 142.5 (Ar),140.3 (Ar), 137.4 (Ar), 136.9 (Ar), 135.9 (Ar), 132.1 (Ar), 131.5, 130.5 (Ar), 129.9 (2 ×ArH), 129.4 (ArH), 129.0 (2 × ArH), 129.0 (2 × ArH), 128.7(2 × ArH), 128.6 (ArH), 127.5 (2 × ArH), 127.0 (2 ×ArH), 126.6 (pyrrole), 124.6 (pyrrole), 123.5 , 123.2 , 121.9 , 118.9 (pyrroleCH), 116.4 (pyrrole), 21.4 (CH3), 21.3 (CH3)and 21.2 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C32H28F3N2O2S+ 561.1818; found561.1826.1,2-Diaminoalkene 17d  was treated with BF3·OEt2  in CH2Cl2 (6.7 mL) according to General Procedure 4 to give the titlecompound 18d  as a yellow solid: mp 158 °Cdec; νmax (film) 3271, 2920, 2859, 1512, 1323, 1250,1157, 1092, and 1034 cm–1; 1H NMR  δ 7.33 , 7.23 , 7.06 , 6.99 , 6.91 , 6.84 , 6.83, 6.80 ,6.77 , 6.23 ,3.77 , 2.34 , 2.29 and 2.27 ; 13C{1H} NMR  δ158.1 (Ar), 142.3 (Ar), 137.0 (Ar), 136.7 (Ar), 135.5 (Ar), 133.0(Ar), 132.1 (Ar), 131.1 (Ar), 129.9 (2 × ArH), 128.9 (2 ×ArH), 128.7 (2 × ArH), 128.6 (2 × ArH), 127.4 (2 ×ArH), 127.2 (pyrrole), 127.0 (2 × ArH), 126.7 (2 × ArH),123.4 (pyrrole), 119.5 (pyrrole CH), 115.0 (pyrrole), 114.0 (2 ×ArH), 55.4 (OCH3), 21.4 (CH3), 21.3 (CH3) and 21.2 (CH3); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C32H30N2NaO3S+ 545.1869;found 545.1858.1,2-Diaminoalkene 4a  and α-aminoketone 16e  were treated with Rh2(OAc)4  in PhMe (10 mL) according to GeneralProcedure 3. During the N–H insertion, spontaneous cyclodehydrationoccurred to give the title compound 18e as a yellow wax: νmax (film) 3264, 3024, 2920, 2866,1493, 1381, 1327, and 1161 cm–1; 1H NMR δ 7.35 , 7.19 , 7.09 , 6.84 , 6.81 , 6.80 , 6.69 , 6.57 , 6.27 , 2.35, 2.28 , 2.25 , 2.24  and 1.92 ; 13C{1H} NMR  δ 142.5 (Ar), 137.9 (Ar), 136.5(Ar), 136.0 (Ar), 135.7 (2 × Ar), 135.6 (Ar), 135.4 (Ar), 132.0(Ar), 131.3 (Ar), 128.9 (2 × ArH), 128.7 (2 × ArH), 128.6(2 × ArH), 128.5 (4 × ArH), 127.3 (pyrrole), 127.3 (2 ×ArH), 127.2 (2 × ArH), 123.4 (pyrrole), 118.6 (pyrrole CH), 113.7(pyrrole), 21.5 (CH3), 21.2 (CH3), 21.2 (CH3), 21.0 (CH3) and 17.7 (2 × CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C34H35N2O2S+ 535.2414; found 535.2423.Triazole 4a and α-aminoketone 16f were treated with Rh2(OAc)4  in PhMe (10 mL) according to General Procedure 3. Duringthe N–H insertion, spontaneous cyclodehydration occurred togive the title compound 18f  as a yellowsolid: mp 150 °C dec; νmax (film) 3268, 3048,2920, 2866, 1412, 1323, 1157, and 1092 cm–1; 1H NMR  δ 7.88–7.83, 7.79 , 7.62–7.58 , 7.55–7.45, 7.40 , 7.34 ,7.28 , 7.21 , 7.10 , 6.89 , 6.83 , 6.73 , 6.29 ,2.36 , 2.27  and 2.16; 13C{1H} NMR  δ 142.5 (naphthyl C), 136.7(Ar), 136.6 (Ar), 136.4 (Ar), 135.6 (Ar), 134.0 (naphthyl C), 133.8(pyrrole), 131.0 (Ar), 130.8 (naphthyl C), 129.2 (2 × ArH), 129.0(2 × ArH), 128.7 (2 × ArH), 128.5 (2 × ArH), 128.4(naphthyl CH), 128.1 (naphthyl CH), 127.4 (2 × ArH), 127.2 (2× ArH), 127.1 (Ar), 127.0 (naphthyl CH), 126.5 (naphthyl CH),125.7 (naphthyl CH), 125.0 (naphthyl CH), 123.3 (pyrrole), 123.1 (naphthylCH), 121.1 (pyrrole CH), 114.6 (pyrrole), 21.4 (CH3), 21.2(CH3) and 21.1 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C35H31N2O2S+ 543.2101;found 543.2109.Triazole 17g  was treated with BF3·OEt2  in CH2Cl2 (3.3mL) according to General Procedure 4 to give the title compound 18g  as a yellow solid. 4-Ethynyltoluene  and 4-toluenesulfonyl azide  were treated with CuTC  inCH2Cl2 (10 mL), followed by α-aminoketone 16g  and Rh2(OAc)4 , and finally BF3·OEt2  accordingto General Procedure 5 to give the title compound 18g : mp 154 °C dec; νmax (film)3271, 3028, 2920, 2866, 1512, 1381, 1323, 1157, and 1092 cm–1; 1H NMR  δ7.19 , 7.14–7.06 , 6.98 , 6.86–6.84, 6.81 , 6.18, 2.37 , 2.32 , 2.29 , 2.25  and 2.01 ; 13C{1H}NMR  δ 142.0 (Ar),137.2 (Ar), 137.2 (Ar), 136.0 (Ar), 135.9 (Ar), 135.2 (Ar), 131.4(Ar), 131.0 (Ar), 129.8 (2 × ArH), 129.6 (2 × ArH), 129.4(2 × ArH), 128.8 (2 × ArH), 128.6 (2 × ArH), 128.4(2 × ArH), 128.3 (2 × ArH), 127.9 (pyrrole), 126.9 (2 ×ArH), 125.9 (pyrrole), 120.6 (pyrrole), 114.6 (pyrrole), 21.4 (CH3), 21.2 (CH3), 21.2 (CH3), 21.1 (CH3) and 12.0 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C33H33N2O2S+ 521.2257; found 521.2256.1,2-Diaminoalkene 17h  was treated with BF3·OEt2  in CH2Cl2 (3.3mL) according to General Procedure 4 to give the title compound 18h  as an orange solid. 4-Ethynyltoluene  and 4-toluenesulfonyl azide  were treated with CuTC  in CH2Cl2 (10 mL), followed by α-aminoketone 16h  and Rh2(OAc)4 , and finally BF3·OEt2  accordingto General Procedure 5 to give the title compound 18h . On a larger scale, 4-ethynyltoluene  and 4-toluenesulfonyl azide  were treated with CuTC  in CH2Cl2 (170 mL), followed by α-aminoketone 16h  and Rh2(OAc)4 , and finally BF3·OEt2  according toGeneral Procedure 5 to give the title compound  as anorange solid: mp 160 °C dec; νmax (film) 3264,3036, 2924, 1516, 1377, 1327, 1157, and 1092 cm–1; 1H NMR  δ7.79–7.76 , 7.73–7.69 , 7.67, 7.52 , 7.47–7.39 , 7.21, 7.08 , 7.02–6.98 , 7.00 , 6.57 , 6.27 , 2.33 , 2.32 and 1.98 ; 13C{1H} NMR δ 142.5 (Ar), 137.4(Ar), 137.0 (Ar), 136.9 (Ar), 136.6 (Ar), 133.6 (naphthyl C), 132.7(Ar), 132.0 (naphthyl C), 131.5 (naphthyl C), 130.0 (2 × ArH),129.5 (2 × ArH), 128.8 (2 × ArH), 128.6 (2 × ArH),127.9 (naphthyl CH), 127.7 (naphthyl CH), 127.5 (naphthyl CH), 127.2(naphthyl CH), 126.9 (2 × ArH), 126.3 (naphthyl CH), 125.7 (pyrrole),125.6 (naphthyl CH), 125.3 (2 × ArH), 125.2 (naphthyl CH), 123.4(pyrrole), 119.9 (pyrrole CH), 115.5 (pyrrole), 21.3 (CH3), 21.1 (CH3) and 21.0 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C35H31N2O2S+ 543.2101;found 543.2109.1,2-Diaminoalkene 17i  was treated with BF3·OEt2  in CH2Cl2 (3.3 mL) according to General Procedure 4 to give the title compound 18i  as a yellow solid: mp 160 °C dec; νmax (film) 3264, 3036, 2920, 2859, 1505, 1389, 1323, 1242,1157, and 1092 cm–1; 1H NMR  δ 7.36 , 7.24 , 7.04, 6.94 , 6.91 , 6.84, 6.83 ,6.82 , 6.80 , 6.17 , 3.82 , 2.30 , 2.29  and 2.28 ; 13C{1H}NMR  δ 158.1 (Ar),142.4 (Ar), 137.4 (Ar), 137.1 (Ar), 136.8 (Ar), 136.4 (Ar), 131.8(Ar), 129.9 (2 × ArH), 129.5 (2 × ArH), 128.7 (2 ×ArH), 128.7 (2 × ArH), 128.6 (2 × ArH), 127.3 (Ar), 127.1(2 × ArH), 126.6 (pyrrole), 125.2 (2 × ArH), 123.3 (pyrrole),119.1 (pyrrole CH), 115.3 (pyrrole), 113.7 (2 × ArH), 55.2 (OCH3), 21.4 (CH3), 21.3 (CH3) and 20.9 (CH3); HRMS (ESI-TOF) m/z [M+ H]+ calcd for C32H31N2O3S+ 523.2050; found 523.2059.1,2-Diaminoalkene 17j  was treated with BF3·OEt2  in CH2Cl2 (3.3 mL) according to General Procedure 4 to give the title compound 18j  as an orange solid. 4-Ethynyltoluene  and 4-toluenesulfonyl azide  were treated with CuTC  in CH2Cl2 (10 mL), followed by α-aminoketone 16j  and Rh2(OAc)4 , and finally BF3·OEt2  accordingto General Procedure 5 to give the title compound 18j : mp 175 °C dec; νmax (film)3264, 3036, 2924, 1597, 1393, 1335, 1161, and 1151 cm–1; 1H NMR  δ8.11 , 7.71 , 7.23 , 7.07 , 7.04 , 6.96–6.90 , 6.83 , 6.74 , 6.32 , 2.31 , 2.30  and 2.25 ; 13C{1H} NMR  δ145.6 (Ar), 143.1 (Ar), 141.4 (Ar), 137.4 (Ar), 137.2 (Ar), 136.8(Ar), 136.5 (Ar), 132.9 (Ar), 129.7 (2 × ArH), 129.6 (2 ×ArH), 128.9 (2 × ArH), 128.9 (2 × ArH), 127.4 (2 ×ArH), 127.1 (2 × ArH), 126.3 (pyrrole), 125.1 (2 × ArH),123.7 (2 × ArH), 121.3 (pyrrole), 120.8 (pyrrole CH), 115.4 (pyrrole),21.3 (CH3), 21.3 (CH3) and 21.0 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C31H28N3O4S+ 538.1795; found 538.1803.1,2-Diaminoalkene 17k  was treated with BF3·OEt2  in CH2Cl2 (3.3 mL) according to General Procedure 4 to give the title compound 18k  as a yellow solid: mp 165 °C dec; νmax (film) 3275, 3036, 2924, 2226, 1605, 1543, 1516, 1393,1327, and 1161 cm–1; 1H NMR  δ 7.65 , 7.52 , 7.22, 7.06 , 6.99 , 6.95–6.90 , 6.84 , 6.74 , 6.27 , 2.31 , 2.30  and 2.30 ; 13C{1H} NMR  δ 143.0 (Ar), 139.2 (Ar), 137.3 (Ar),137.1 (Ar), 136.9 (Ar), 136.5 (Ar), 132.8 (Ar), 132.0 (2 × ArH),129.7 (2 × ArH), 129.6 (2 × ArH), 128.9 (2 × ArH),128.9 (2 × ArH), 127.5 (2 × ArH), 127.0 (2 × ArH),126.4 (pyrrole), 125.1 (2 × ArH), 121.7 (pyrrole), 120.5 (pyrroleCH), 119.4 (pyrrole), 115.3 (C≡N), 109.0 (Ar), 21.4 (CH3), 21.3 (CH3) and 21.0 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C32H28N3O2S+ 518.1897;found 518.1904.1,2-Diaminoalkene 17l  was treated with BF3·OEt2  in CH2Cl2 (3.3 mL) according to General Procedure 4 to give the title compound 18l  as a yellow solid: mp 160 °C dec; νmax (film) 3268, 2924, 1501, 1389, 1157, and 1092 cm–1; 1H NMR  δ7.36 , 7.24 , 7.18 , 7.05 , 6.95 , 6.93 , 6.88 , 6.85 , 6.84 , 6.18 , 2.31 and 2.30 ; 13C{1H} NMR δ 142.8 (Ar), 137.2(Ar), 137.1 (Ar), 136.9 (Ar), 136.7 (Ar), 132.6 (Ar), 132.4 (Ar),131.8 (Ar), 129.9 (2 × ArH), 129.5 (2 × ArH), 128.8 (2 ×ArH), 128.8 (2 × ArH), 128.6 (2 × ArH), 128.3 (2 ×ArH), 127.0 (2 × ArH), 126.9 (pyrrole), 125.2 (2 × ArH),122.4 (pyrrole), 119.6 (pyrrole CH), 115.2 (pyrrole), 21.5 (CH3), 21.3 (CH3) and 21.0 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C31H28ClN2O2S+ 527.1555;found 527.1559.1,2-Diaminoalkene 17m  was treated with BF3·OEt2  in CH2Cl2 (3.3 mL) according to General Procedure 4 to give the title compound 18m  as a yellow solid: mp 187 °C dec; νmax (film) 3268, 2920, 1516, 1397, 1327, 1161, and 1092 cm–1; 1H NMR  δ 7.32 ,7.24 , 7.18 , 7.12 , 7.05 , 7.03, 6.86 , 6.85 , 6.82 , 6.66 , 6.32 , 2.35 , 2.34  and 2.28 ; 13C{1H} NMR  δ 142.5 (Ar), 137.3 (Ar), 137.1 (Ar), 136.9(Ar), 135.6 (Ar), 130.7 (Ar), 130.7 (thiophene C2), 129.5 (2 ×ArH), 128.9 (2 × ArH), 128.8 (2 × ArH), 128.4 (thiopheneCH), 127.3 (2 × ArH), 127.1 (2 × ArH), 126.7 (thiopheneCH), 126.4 (thiophene CH), 125.7 (2 × ArH), 125.6 (pyrrole),123.6 (pyrrole), 120.4 (pyrrole CH), 116.5 (pyrrole), 21.4 (CH3), 21.2 (CH3) and 21.0 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C29H27N2O2S2+ 499.1508; found 499.1517.1,2-Diaminoalkene 17n  was treated with BF3·OEt2  in CH2Cl2 (3.3 mL) according to General Procedure 4 to give the title compound 18n  as a yellow solid: mp 75 °C dec; νmax (film) 3275, 2924, 1516, 1393, 1323, 1250, 1157, and 1092cm–1; 1H NMR  δ 7.31 , 7.24 , 7.06 , 7.05 , 6.94 , 6.90 , 6.85 , 6.82, 6.65 , 6.15 , 3.78 ,2.34 , 2.31  and 2.27; 13C{1H} NMR  δ 158.7 (Ar), 142.4 (Ar), 137.4(Ar), 137.1 (Ar), 136.5 (Ar), 135.5 (Ar), 131.8 (Ar), 131.3 (2 ×ArH), 131.1 (Ar), 129.5 (2 × ArH), 129.0 (2 × ArH), 128.7(2 × ArH), 127.4 (2 × ArH), 127.1 (2 × ArH), 125.3(2 × ArH), 123.5 (pyrrole), 122.7 (pyrrole), 119.2 (pyrrole CH),115.2 (pyrrole), 113.5 (2 × ArH), 55.1 (OCH3), 21.4(CH3), 21.2 (CH3) and 21.0 (CH3);HRMS (ESI-TOF) m/z [M + H]+ calcd for C32H31N2O3S+ 523.2050; found 523.2057.1,2-Diaminoalkene 17o  was treated with BF3·OEt2  in CH2Cl2 (3.3 mL) according to General Procedure 4 to give the title compound 18o  as a brown solid: mp 80 °C dec; νmax (film) 3271, 3036, 2928, 1709, 1593, 1516, 1492, 1393,1246, 1157, and 1092 cm–1; 1H NMR  δ 7.41 , 7.22 , 7.19 , 7.17 , 7.00 , 6.97 , 6.69, 6.15 , 5.80–5.76 , 2.37 , 2.32 ,2.30 , 2.10–2.03 , 1.57–1.52 , 1.48–1.42  and 1.39–1.32 ; 13C{1H} NMR  δ 142.6 (Ar), 138.1 (Ar), 137.2 (Ar), 136.5 (Ar),135.2 (Ar), 134.5 (pyrrole), 131.5 (=CH), 131.2 (Ar), 129.6 (2 ×ArH), 128.9 (2 × ArH), 128.8 (2 × ArH), 128.7 (=C), 127.4(2 × ArH), 127.2 (2 × ArH), 124.0 (2 × ArH), 123.0(pyrrole), 118.1 (pyrrole CH), 114.4 (pyrrole), 28.2 (CH2), 25.7 (CH2), 22.4 (CH2), 21.5 (CH2), 21.4 (CH3), 21.1 (CH3) and 21.0 (CH3); HRMS (ESI-TOF) m/z [M+ H]+ calcd for C31H33N2O2S+ 497.2257; found 497.2265.1,2-Diaminoalkene 17p  was treated with BF3·OEt2  in CH2Cl2 (3.3 mL) according to General Procedure 4 to give the titlecompound 18p  as a yellow solid. 4-Ethynyltoluene and 4-methoxybenzenesulfonyl azide were treated with CuTC  in CH2Cl2 (10 mL), followed by α-aminoketone 16a  and Rh2(OAc)4 , and finally BF3·OEt2  accordingto General Procedure 5 to give the title compound 18p : mp 150 °C dec; νmax (film) 3271,3020, 2920, 1593, 1501, 1389, 1323, 1258, 1153, and 1096 cm–1; 1H NMR  δ7.33 , 7.27 , 7.06 , 7.05 , 6.95 , 6.93 , 6.87 , 6.86, 6.47 ,6.17 , 3.76 , 2.34 , 2.31  and 2.29 ; 13C{1H} NMR  δ 162.3 (Ar), 137.4 (Ar), 136.7 (Ar), 136.5(Ar), 135.5 (Ar), 131.9 (Ar), 131.6 (Ar), 131.1 (Ar), 129.9 (2 ×ArH), 129.5 (2 × ArH), 129.1 (2 × ArH), 129.0 (2 ×ArH), 128.8 (2 × ArH), 127.4 (2 × ArH), 127.3 (pyrrole),125.2 (2 × ArH), 123.5 (pyrrole), 119.4 (pyrrole CH), 115.4 (pyrrole),113.2 (2 × ArH), 55.3 (OCH3), 21.2 (CH3), 21.1 (CH3) and 21.0 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C32H31N2O3S+ 523.2050;found 523.2058.1,2-Diaminoalkene 17q  was treated with BF3·OEt2  in CH2Cl2 (3.3 mL) according to General Procedure 4 to give the title compound 18q  as an orange solid: mp 180 °C dec; νmax (film) 3271, 3036, 2920, 2862, 1516, 1404, 1389, 1346,1161, and 1092 cm–1; 1H NMR  δ 7.80 , 7.53 , 7.26, 7.06 , 7.05 , 6.94, 6.93 , 6.88 , 6.87, 6.53 , 2.32 , 2.31  and 2.29 ; 13C{1H} NMR  δ 149.3 (Ar), 145.7 (Ar), 137.4 (Ar), 137.1 (Ar),136.8 (Ar), 136.2 (Ar), 132.6 (Ar), 130.7 (Ar), 129.9 (2 × ArH),129.6 (2 × ArH), 129.1 (2 × ArH), 128.9 (2 × ArH),128.2 (2 × ArH), 127.4 (2 × ArH), 127.0 (pyrrole), 125.2(2 × ArH), 123.7 (pyrrole), 123.2 (2 × ArH), 119.7 (pyrroleCH), 114.0 (pyrrole), 21.2 (CH3), 21.0 (CH3)and 21.0 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C31H28N3O4S+ 538.1795; found 538.1805.1,2-Diaminoalkene 17r was treated with BF3·OEt2  in CH2Cl2 (3.3 mL) accordingto General Procedure 4 to give the title compound 18r  as an orange solid: mp 93–94 °C; νmax (film) 3268, 2924, 1516, 1393, 1319, and 1153 cm–1; 1H NMR  δ7.51 , 7.22 , 7.15 , 7.10 , 7.09 , 7.02 , 6.96 , 5.92 , 2.37, 2.33 , 2.32  and 2.29 ; 13C{1H} NMR  δ137.5 (Ar), 137.4 (Ar), 136.7 (Ar), 136.3 (Ar), 132.1 (Ar), 131.0(Ar), 130.2 (2 × ArH), 129.6 (2 × ArH), 129.5 (2 ×ArH), 129.2 (2 × ArH), 127.9 (2 × ArH), 127.5 (pyrrole),125.3 (2 × ArH), 123.7 (pyrrole), 119.5 (pyrrole CH), 115.3 (pyrrole),40.7 (Ms), 21.3 (CH3), 21.2 (CH3) and 21.0 (CH3); HRMS (ESI-TOF) m/z [M+ H]+ calcd for C26H27N2O2S+ 431.1788; found 431.1797.1,2-Diaminoalkene 2Cl2 (10 mL), followed by α-aminoketone 16e  and Rh2(OAc)4 , and finally BF3·OEt2  accordingto General Procedure 5 to give the title compound 18s  as an orange solid: mp 140 °C dec; νmax (film) 3268, 2924, 2226, 1609, 1566, 1516, 1327, 1292,1250, 1161, 1092, and 1034 cm–1; 1H NMR δ 7.64 , 7.52 , 7.25 , 7.06 , 6.98 , 6.93, 6.86 , 6.80 , 6.65, 6.25 , 3.78, 2.31  and 2.31 ; 13C{1H} NMR  δ 159.0 (Ar), 143.0 (Ar), 139.2(Ar), 137.1 (Ar), 136.9 (Ar), 136.7 (Ar), 132.7 (Ar), 132.0 (2 ×ArH), 131.1 (2 × ArH), 129.7 (2 × ArH), 128.9 (2 ×ArH), 127.5 (2 × ArH), 127.1 (2 × ArH), 125.2 (2 ×ArH), 121.7 (pyrrole), 121.6 (pyrrole), 120.2 (pyrrole CH), 119.4(pyrrole), 115.1 (C≡N), 113.7 (2 × ArH), 109.0 (Ar), 55.1(OCH3), 21.4 (CH3) and 21.0 (CH3);HRMS (ESI-TOF) m/z [M + H]+ calcd for C32H28N3O3S+ 534.1846; found 534.1851.1-Ethynyl-4-methoxybenzene  and 4-toluenesulfonyl azide  were treated with CuTC  inCH2Cl2 (10 mL), followed by α-aminoketone 16g  and Rh2(OAc)4 , and finally BF3·OEt2  accordingto General Procedure 5 to give the title compound 18t  as an orange solid: mp 70 °C dec; νmax (film) 3275, 2920, 2851, 1512, 1462, 1381, 1323, 1246,1157, 1092, and 1030 cm–1; 1H NMR  δ 7.20 , 7.13–7.05 , 6.96 , 6.88 , 6.82 , 6.59, 6.03 , 3.74, 2.36 , 2.32 , 2.29  and 2.01 ; 13C{1H} NMR  δ 158.2 (Ar), 142.1 (Ar), 137.3 (Ar),137.2 (Ar), 135.9 (Ar), 135.3 (Ar), 131.4 (Ar), 131.2 (2 × ArH),130.8 (Ar), 129.5 (2 × ArH), 129.4 (2 × ArH), 128.8 (2 ×ArH), 128.6 (2 × ArH), 128.3 (2 × ArH), 127.0 (2 ×ArH), 125.7 (pyrrole), 123.4 (pyrrole), 120.4 (pyrrole), 114.5 (pyrrole),113.2 (2 × ArH), 55.0 (CH3), 21.4 (CH3),21.2 (CH3), 21.1 (CH3) and 11.9 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C33H33N2O3S+ 537.2206; found 537.2207.1-Ethynyl-4-methoxybenzene  and 4-toluenesulfonyl azide  were treated with CuTC  inCH2Cl2 (10 mL), followed by α-aminoketone 16u  and Rh2(OAc)4 , and finally BF3·OEt2  according to General Procedure5 to give the title compound 18u  as a yellowsolid: mp 66 °C dec; νmax (film) 3271, 3005,2924, 2862, 1516, 1323, and 1161 cm–1; 1H NMR  δ 7.37 , 6.98 , 6.91 , 6.82, 6.81 , 6.59 , 6.39, 6.14 ,2.30 , 2.27 , 2.26, 1.85 , 0.82  and 0.51 ; 13C{1H} NMR  δ142.5 (Ar), 137.6 (Ar), 136.8 (Ar), 136.4 (Ar), 136.0 (Ar), 130.2(Ar), 129.5 (2 × ArH), 129.3 (2 × ArH), 128.8 (2 ×ArH), 128.5 (2 × ArH), 127.3 (pyrrole), 127.2 (2 × ArH),126.3 (pyrrole), 125.1 (2 × ArH), 117.6 (pyrrole), 116.9 (pyrroleCH), 21.5 (CH3), 21.2 (CH3), 20.9 (CH3), 7.6 (2 × cyclopropane CH2) and 5.7 (cyclopropane);HRMS (ESI-TOF) m/z [M + H]+ calcd for C28H29N2O2S+ 457.1944; found 457.1943.4-Ethynyltoluene  and4-toluenesulfonyl azide  were treatedwith CuTC  in CH2Cl2 (10 mL), followed by α-aminoketone 16v  and Rh2(OAc)4 , and finally BF3·OEt2  according to General Procedure5 to give the title compound 18v  as a yellowsolid: mp 80 °C dec; νmax (film) 3271, 3063,2924, 1516, 1389, 1327, and 1161 cm–1; 1H NMR  δ 7.19 , 7.15–7.04 ,7.01–6.98 , 6.97 , 6.82 , 6.69, 6.08 , 2.31 , 2.29  and 2.23 ; 13C{1H} NMR  δ 142.2 (Ar), 137.5 (2 × Ar), 136.8 (Ar),136.4 (Ar), 136.2 (Ar), 133.3 (Ar), 131.0 (pyrrole), 130.5 (ArH),130.1 (2 × ArH), 129.9 (ArH), 129.5 (2 × ArH), 128.8 (2× ArH), 128.8 (2 × ArH), 127.4 (Ar), 126.8 (2 × ArH),126.5 (ArH), 125.4 (ArH), 125.2 (2 × ArH), 122.6 (pyrrole), 120.3(pyrrole CH), 116.3 (pyrrole), 21.4 (CH3), 21.3 (CH3), 20.9 (CH3) and 20.7 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C32H31N2O2S+ 507.2101;found 507.2111.4-Ethynyltoluene  and4-toluenesulfonyl azide  were treatedwith CuTC  in CH2Cl2 (10 mL), followed by α-aminoketone 16a  and Rh2(OAc)4 , and finally BF3·OEt2  according to GeneralProcedure 5 to give the title compound 18w as a yellow solid: mp 90 °C dec; νmax (film)3275, 3024, 2920, 2866, 1510, 1505, 1412, 1389, 1323, 1223, 1157,and 1092 cm–1; 1H NMR  δ 7.29–7.23 ,7.08–7.04 , 7.06 , 6.99 , 6.93 , 6.86 , 6.83 , 6.81 , 6.21 , 2.35 , 2.32  and 2.28 ; 13C{1H}NMR  δ 161.9 , 142.6 (Ar),137.1 (Ar), 137.1 (Ar), 136.8 (Ar), 135.7 (Ar), 131.9 , 131.0(pyrrole), 130.8 (Ar), 129.6 (2 × ArH), 129.0 (2 × ArH),128.8 (2 × ArH), 127.4 (2 × ArH), 127.0 (2 × ArH),126.4 ,125.3 (2 × ArH), 123.7 (pyrrole), 119.6 (pyrrole CH), 115.6 (pyrrole),115.0 , 21.4 (CH3), 21.2 (CH3) and 20.9(CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C31H28FN2O2S+ 511.1850; found 511.1856.1-Ethynyl-4-fluorobenzene  and 4-toluenesulfonyl azide were treated with CuTC  in CH18a  in 1,2-dichloroethane(2.0 mL) at 0 °C (ice bath). The mixture was heated at 90 °C(heating block) in a sealed vial for 2.5 h. The reaction mixture wascooled to ambient temperature, and the reaction was quenched by theaddition of ethylenediamine (2 drops) followed by 1 M aqueous NaOH(2.0 mL). The aqueous phase was extracted with dichloromethane (3× 2.0 mL), and the combined organic layers were washed with brine,dried (MgSO4), and concentrated in vacuo. Purificationby flash column chromatography  gave the title compound 23a  asa yellow oil: νmax (film) 3402, 3322, 3028, 2920,2859, 1516, and 1389 cm–1; 1H NMR  δ 7.52 , 7.23 , 7.12–7.00 , 6.85 ,3.35 , 2.38  and 2.32; 13C{1H} NMR  δ 138.1 (Ar), 135.4 (Ar), 135.4(Ar), 135.3 (Ar), 131.9 (pyrrole), 129.5 (2 × ArH), 129.5 (2× ArH), 129.2 (3 × ArH and Ar), 128.9 (2 × ArH), 128.6(pyrrole), 127.1 (2 × ArH), 124.5 (2 × ArH), 119.2 (pyrroleCH), 117.9 (Ar), 116.9 (pyrrole), 21.2 (CH3), 21.1 (CH3) and 20.9 (CH3); HRMS (ESI-TOF) m/z [M + H]+ calcd for C25H25N2+ 353.2012; found 353.2014.Triflic acid  was added to a solutionof pyrrole


Augmented reality (AR) is an emerging technology that can overlay computer graphics onto the real world and enhance visual feedback from information systems. Within the past several decades, innovations related to AR have been integrated into our daily lives; however, its application in medicine, specifically in minimally invasive spine surgery (MISS), may be most important to understand. AR navigation provides auditory and haptic feedback, which can further enhance surgeons’ capabilities and improve safety.The purpose of this article is to address previous and current applications of AR, AR in MISS, limitations of today's technology, and future areas of innovation.A literature review related to applications of AR technology in previous and current generations was conducted.AR systems have been implemented for treatments related to spinal surgeries in recent years, and AR may be an alternative to current approaches such as traditional navigation, robotically assisted navigation, fluoroscopic guidance, and free hand. As AR is capable of projecting patient anatomy directly on the surgical field, it can eliminate concern for surgeon attention shift from the surgical field to navigated remote screens, line-of-sight interruption, and cumulative radiation exposure as the demand for MISS increases.AR is a novel technology that can improve spinal surgery, and limitations will likely have a great impact on future technology. Augmented reality (AR) is an emerging technology that can overlay computer graphics onto the real world and enhance visual feedback from information systems . Based oOver the past several decades, AR has grown to be an area of interest across many surgical fields, especially with its role in spinal surgery. Recently, AR systems have been implemented in treatment of degenerative cervical, thoracic, and lumbar spine diseases , 3. StudAlthough AR is a novel technology that may distinguish itself from other state-of-the-art navigation systems, it is still in its nascency, and several limitations are important to recognize, such as mechanical and visual discomfort  and delaThe purpose of this article is to address previous and current applications of AR, AR navigation in MISS, limitations of today's technology, and future areas of innovation.A systematic review was conducted using the PRISMA  guidelines.augmented reality, robotics-assisted surgery, navigation, heads-up display, minimally invasive surgery, spine surgery, pedicle screw, and accuracy were used and combined by means of Boolean operators AND and OR under English search. Categories were developed to classify studies as either clinical trial , meta-analysis, randomized controlled trials, review articles, systematic review, and additional sources. The criterion for selecting the articles was published or supported by an indexed scientific database  by eliminating selection bias, detection bias, reporting bias, and other biases. Ethical approval was not applicable for conducting this systematic review and meta-analysis.Sword of Damocles,” was created by Ivan Sutherland, a Harvard professor and computer engineer  lines that appear stationary in the room  on the guidance images; however, other guidance systems split the attention almost 50/50 between the patient and the monitor . AdditioAside from attention shift, another common limitation of RNA guidance is line-of-sight interruption . During Patient anatomy is obtained by automated segmentation of the intraoperative cone beam CT scan. The surgeon is also able to see 2D sagittal and axial projections within the headset , 4B. TheRadiation exposure for spine surgeons, OR staff, and patients has been a concern for many years . AccordiOver the years, intraoperative imaging and surgical approaches have evolved with spine surgery. This generally guided surgeons to less invasive approaches, such as MISS techniques. Stanford Medicine reported that MISS techniques and RAN integration have shown shorter operating times and reduced pain and discomfort in patients . FurtherTechnologies to reduce intraoperative radiation have real potential to impact long-term risks. As wearable and independent of navigation monitors, AR guidance can avoid attention shift, decrease OR clutter, and does not use or require ionizing radiation for surgical guidance. Studies such as Felix et al. have documented recent advancements in AR as a “paradigm shift” in its application in a variety of surgical fields, including orthopedics, neurosurgery, and spine surgery .Although AR is a novel technology that may distinguish itself from other state-of-the-art navigation systems, it is still in its nascency and several technical limitations are important to recognize. First, mechanical and visual discomfort may arise from AR devices such as AR headwear (AR-HMD) . FurtherDelays in the surgical learning curve associated with AR may be attributed to a surgeon's ability to adapt and may depend on a generation of surgeons who grew up playing video games –18. SpinLastly, there is a limited amount of literature in regard to AR assistance with workflow related to pedicle screw placement and no universally accepted standard method to grade screw accuracy and/or safety . Common via hepatic feedback, and reduce intraoperative complications (With current advancements in the last several years, the use of AR in spinal surgery promises an exciting future. Future updates/versions of AR technology and wearable devices may improve the ability to manipulate display and radiographic scans, enhance surgeon's alertness when approaching critical structures ications . In addiFurthermore, several RAN and AR systems for spine surgery have been released and tested in numerous clinical studies . AlthougThe role of AR in spine surgery is a rapidly evolving field where new technology and surgical techniques can help maximize surgical efficiency, precision, and accuracy. With collaborations from clinicians, engineers, and video game designers, this technology can profoundly improve components of MISS. Thus, it is conceivable that within the next few years surgeons will be wearing AR glasses during patient consultation, rehabilitation, training, and surgery. Such advancements, among others, will continue to drive the value of AR 3D navigation in MISS.


Technological advances have transformed vascular intervention in recent decades. In particular, improvements in imaging and data processing have allowed for the development of increasingly complex endovascular and hybrid interventions. Augmented reality (AR) is a subject of growing interest in surgery, with the potential to improve clinicians’ understanding of 3D anatomy and aid in the processing of real-time information. This study hopes to elucidate the potential impact of AR technology in the rapidly evolving fields of vascular and endovascular surgery.The aim of this review is to summarize the fundamental concepts of AR technologies and conduct a scoping review of the impact of AR and mixed reality in vascular and endovascular surgery.. Studies were selected through a blinded process between 2 investigators (JE and AS) and assessed using data quality tools.A systematic search of MEDLINE, Scopus, and Embase was performed in accordance with the PRISMA  guidelines. All studies written in English from inception until January 8, 2021, were included in the search. Combinations of the following keywords were used in the systematic search string:  AND (“vascular surgery” OR “endovascular”)heads up fusion imaging and AR head-mounted displays being the most commonly applied clinically. AR applications included guiding open, robotic, and endovascular surgery while minimizing dissection, improving procedural times, and reducing radiation and contrast exposure.AR technologies have had a number of applications in vascular and endovascular surgery. Most studies  used 3D imaging of computed tomography angiogram–derived images of vascular anatomy to augment clinicians’ anatomical understanding during procedures. A wide range of AR technologies were used, with AR has shown promising developments in the field of vascular and endovascular surgery, with potential benefits to surgeons and patients alike. These include reductions in patient risk and operating times as well as in contrast and radiation exposure for radiological interventions. Further technological advances are required to overcome current limitations, including processing capacity and vascular deformation by instrumentation. Emerging technologies are transforming vascular surgery at a rapid pace. In particular, the introduction of endovascular techniques has opened the way for a Cambrian explosion of technological evolution in terms of both hardware  and softOne such technology is augmented reality (AR), which aims to enhance clinicians’ ability by offering intuitive augmentation of the real environment with computer-generated real-time input of virtual information. AR lies on the continuum from virtual reality (VR), in which the user is immersed in a completely virtual setting, to real life. AR allows for minimal interaction between the virtual and real worlds, whereas mixed reality (MR) involves a combination of the real and virtual worlds where both elements are able to interact .Complications in vascular surgery such as wound infections are associated with the extent of dissection, size of the wound, and duration of the surgery . AnatomiSurgical AR uses a range of technologies, including everyday smartphone devices  and commAcross a number of surgical specialties and subspecialties, the potential of AR as an important training tool has been identified . With inLiterature on the applicability of AR in vascular surgery is extremely limited . A recenThis scoping review aimed to systematically search the literature, identify the current applications of AR in vascular and endovascular surgery, and summarize key results and learning points while identifying avenues and gaps for future research in this evolving field.A scoping review was chosen after advice from PROSPERO , and the PRISMA-ScR   was usedThe inclusion criteria were (1) studies in the English language, (2) a minimum of level V evidence using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence, (3) use of AR in vascular or endovascular surgery, and (4) applicability to clinical practice or training reported.The exclusion criteria were (1) review articles or conference abstracts, (2) non–English-language articles, (3) articles lacking an available full text, (4) use of AR outside of vascular or endovascular surgery, and (5) use only of VR.A systematic search of the MEDLINE, Scopus, and Embase databases was performed, allowing for access to a range of global clinical, scientific, and engineering research. All studies written in English from inception until January 8, 2021, were included in the search.The following keywords were used in the systematic search string for all 3 database searches:  AND (“vascular surgery” OR “endovascular”). No limits were applied.First, a blinded and independent process of selection based on titles and abstracts was performed without collusion by 2 authors (AS and JE), with a third author (JS) consulted with regard to discrepancies. Next, a selection of eligible studies was conducted by analyzing the full texts.Each study was evaluated individually, and the following variables were sought for data collection: year of study, category , applied study or concept and design, number of patients , risk of bias (see the following section for the tools used), characteristics of the study group and operators, methods and outcomes, imaging type, and type of display (if applicable).Yes, a score of 0.5 was assigned for unclear, and a score of 0 was assigned for no. The results were presented as percentages. A higher percentage represented a reduced risk of bias.The quality of the data was evaluated using the Cochrane tools Risk of Bias 2 for randomized trials and Risk of Bias In Non-randomized Studies of Interventions for nonrandomized trials ,14. For Data were extracted from eligible studies into evidence tables to summarize the following: year of publication, type of study design, number of patients, method, and outcome. A second table presents more technical aspects of the research, including the type of imaging, methods for tracking or registration, and display. The data collected in the evidence tables were used to define the main themes of discussion. Any data related to the application of AR in vascular and endovascular surgery could be synthesized.A total of 726 articles were identified from the initial search across the 3 databases, with 32 (4.4%) meeting the inclusion and exclusion criteria and being included in the final results. Please see A total of 32 articles applicable to vascular and endovascular surgery met the criteria for inclusion. The included articles were sorted into three categories: open vascular surgery, endovascular surgery , and training  of the studies. The Cochrane risk of bias assessment was not used as no randomized trials were included in our review. Among the clinical studies, 6% (2/32) were cohort studies ,19, whic of the sconcept and design to reflect the early stage of this technology in vascular surgery and those that conducted research directly applied to surgery, training, or simulation.The articles were further subdivided into studies that focused on The proportion of studies related to concept development of AR was 38% (12/32), whereas the rest were applied to clinical and simulation contexts. Of the 32 studies, 29 (91%) involved deriving digital structures of blood vessels from clinical imaging , often by thresholding via a Hounsfield scale, for example, and then using a 3D computer-generated surface mesh, refining the mesh by filling holes or defects into a model and sometimes using a slicer to break up the model into its different anatomical sections .Registration and tracking are essential components of AR, allowing for the alignment of virtual and real data in a usable way. Registration is commonly performed using markers, where a particular pattern or anatomical landmark in the real world is used as a reference corresponding to a virtual marker derived from medical imaging . This caChallenges with these techniques include the deformability of the anatomy; for example, when stiff endovascular devices are inserted into blood vessels. These changes can cause registration errors, which can be clinically significant, for example, with complex visceral anatomy in endovascular aneurysm repair (EVAR). Groher et al  proposedAlternatively, intravascular US on the tip of catheters can be used to create a 3D model of blood vessels during endovascular procedures with magnetic trackers to orientate the catheter in real time, as proposed by Shi et al . ParriniGiven the inherent reliance of endovascular procedures on imaging, the potential benefits of AR were identified early, in particular to improve clinicians’ understanding of 3D anatomy during critical steps as well as to reduce time and radiation and contrast exposure . Image oEVAR is increasingly being performed for the repair of both complex and conventional infrarenal abdominal aortic aneurysms in the elective and emergency settings.AR visualization has now been used in planning and EVAR navigation, with a case report by Rynio et al  describiA “3D road map” published in 2013 was developed by Fukuda et al  using prFusion imaging has been used for endovascular navigation in hybrid vascular operating theaters, particularly in complex fenestrated EVARs. This uses preoperative 3D CT imaging to overlay vascular structures onto perioperative 2D fluoroscopy images with the aim of reducing fluoroscopy time, contrast agent dosing, and overall operating time. This can also be used in a conventional operating theater with a mobile C-arm with good results for conventional aortic endografting, as reported by Kaladji et al . KoutouzKaladji et al  went on A series of 101 patients by Schulz et al  in 2016 Koutouzi et al  describeA common problem with image overlay techniques is the nondeformability of a rigid 3D model created from a preoperative CT scan. Garcia-Vasquez et al  attempteEndovascular techniques are being applied to increasingly complex surgical problems in patients with comorbidities. The potential to reduce radiation and contrast exposure while navigating tortuous vessels makes the application of AR technology more attractive.Lu et al  describeThe work of Goudeketting et al  focused Swerdlow et al  retrospeEndovascular venous intervention, compared with arterial intervention, can be more challenging because of the lack of landmarks from vessel calcification and reduced vessel wall thickness. Schwein et al  used ima“Traditional” open vascular surgery has increasingly been replaced by novel endovascular techniques, which, in combination with problems with tissue deformation, as previously described, may explain why AR is less well researched in this field.The use of a new image overlay system has been demonstrated successfully in lower limb revascularization surgery by Mochazuki et al . This syModern-day mobile phones have multiple sensors that may be used for AR-assisted surgery. The benefits of easy accessibility (most operators have access to a mobile phone) and cost make them an attractive option. An AR-assisted surgery system was developed by Aly  to proviThe use of AR with robot-assisted surgery is of increasing academic interest worldwide. Pietrabissa et al  successfPublished studies on AR vascular and endovascular training were limited in our review to 16% (5/32) of the papers. Of these 5 papers, 1 (20%) applied this to training vascular surgeons, whereas 4 (80%) focused on design concepts.Unity, ARToolKit, and Pro/ENGINEER. A model aorta was created with the potential for merging with VR and AR tracking technologies to create an accurate training and educational tool for application to both open and endovascular training.Mangina et al  tested tBartesaghi et al  used simSimilarly, Anderson et al  describeCrowley et al ,51 builtAn AR system for US-guided endovascular surgical training was devised by Cheng et al . Live USRudarakanchana et al  applied Our review demonstrates that the most used modality for obtaining data for display is CT angiography , with CBThe reviewed studies demonstrate that AR in surgery often relies on the registration of a virtual image or object onto the real patient using a tracking method, which can trace the real environment and place virtual objects in the correct position and orientation. Our study revealed a wide range of applications of AR in vascular surgery. Image overlay technology is increasingly used, with its value being reported in endovascular treatment of peripheral arterial disease , deep vestretching out of vessels  with rigid stent delivery systems. Emerging technologies offer novel solutions for improving the real-time accuracy of overlaid data. Robust deformable registration algorithms or intraoperative real-time 3D scanners are potential solutions to assist AR-guided surgery on soft or deformable structures. In particular, 3D and intravascular US offer radiation- and contrast-free modalities to create real-time images for intraoperative use [However, concerns remain regarding the accuracy of image registration, especially with more complex anatomies . A commotive use , whereastive use . The inttive use .AR HMDs allow the wearer hands-free access to virtual data overlaid directly onto the patient. Several studies with EVAR in particular have shown early promise that they can reduce the need for radiation and contrast exposure while improving accuracy ,27,31. SMost of the included studies  described small-scale implementations of AR with limited study participants and a wide range of AR hardware and software platforms in their research. Only 44% (14/32) of the studies included human study populations. As AR becomes more ubiquitous for vascular surgery, more evidence will become available, and we believe that these limitations will pose less of an issue.A significant proportion of the studies were preclinical in their applications and demonstrated proof-of-concept findings. Nevertheless, AR solutions are applicable to a wide spectrum of fields in vascular surgery, including those highlighted in this scoping review.Three databases  were searched for this review, allowing for a broad assessment of the current impact of AR clinically and educationally while also scoping potential future applications. However, in this fast-moving field, AR applications under development by private enterprises were not included in the contents of our review. Although our selection criteria focused on vascular and endovascular surgery, there is significant crossover with work applied to other medical and surgical specialties, and wider development within interventional radiology and allied surgical specialties will further inform applications within vascular and endovascular surgery.AR has shown potential to enhance accuracy and reduce procedural time, radiation exposure, and contrast dose in a range of vascular surgery applications by digitally augmenting the clinicians’ procedural ability, reducing surgical risk, and improving patient outcomes. Clinicians, who demand high levels of accuracy and patient safety, should be aware of potential technical pitfalls when using AR technology on patients but should also be aware of the potential benefits. AR has also been shown to be an increasingly valuable tool in surgical simulation and education. As technology improves, it can be expected that AR will become increasingly relied upon as an arrow in the surgical quiver and that more applications will be found for AR, which could benefit clinicians. Future development and studies should assess whether the use of AR affords improvements in patient experience and in clinical effectiveness as objective measures of improvement in outcomes and cost-effectiveness of this technology.


Androgen receptor (AR) is a potential therapeutic target in triple-negative breast cancer (TNBC). We aimed to elucidate the association of AR expression with glucose metabolic features in TNBC.max) of tumors were compared with AR expression. In GSE135565 dataset, glycolysis score was calculated by the pattern of glycolysis-related genes, and of which association with SUVmax and AR gene expression were analyzed.Two independent datasets were analyzed: FDG PET data of our institution and a public dataset of GSE135565. In PET analysis, patients with TNBC who underwent pretreatment PET between Jan 2013 and Dec 2017 were retrospectively enrolled. Clinicopathologic features and maximum standardized uptake value (SUVmax was lower in AR-positive tumors (P < 0.001) and correlated with lower AR expression . In multivariate analysis, AR was a deterministic factor for low SUVmax (P = 0.012), along with other key clinicopathologic features. In the GSE135565 dataset, AR expression also exhibited a negative correlation with SUVmax  and the glycolysis score .A total of 608 female patients were included in the PET data of our institution. SUVLow glucose metabolism is a signature of AR expression in TNBC. It is suggested that evaluation of AR expression status needs to be considered in clinical practice particularly in TNBC with low glucose metabolism. Triple-negative breast cancer (TNBC) is defined as breast cancer without detectable estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)/neu gene overexpression . Althoug18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in clinical practice. Glucose metabolism is one of the key characteristics and a significant prognostic marker in many cancers. Thus, the association of glucose metabolism with a specific gene expression or mutation has been investigated regarding crucial genes, such as EGFR or ALK  for non-parametric test. Chi-square test was used for comparison of AR positivity according to the clinical characteristics. Mann-Whitney U test were used for comparison of SUVP = 0.001) and low histologic grade   were included in the analysis. Most of the cases were invasive ductal carcinoma , and 473 cases (77.8%) were histological grade III. Lymph node metastasis was present in 314 patients (51.6%). Tumor size was larger than 2.0 cm in 402 patients (66.1%). Patient characteristics are summarized in < 0.001) . There wmax was 11.0 ± 7.1 (range 0.8–51.5). SUVmax was significantly higher in tumors of large size, positive lymph node metastasis, high histologic grade, and high Ki-67 index . SUVmax was significantly different between AR-positive and AR-negative tumors, regardless of cutoff values for AR positivity , AR expression was selected as a significant factor for determining SUVmax (P = 0.012), along with tumor size (P < 0.001), presence of lymph node metastasis (P < 0.001), and histologic grade (P < 0.001)  . In addi01) Click here for additional data file.S2 TableAR: androgen receptor.(DOCX)Click here for additional data file.S3 TableAR: androgen receptor.(DOCX)Click here for additional data file.