functionalized , nitrogen - containing heterocycles constitute a widespread structural motif in biologically active compounds(1 ) and an invaluable template for chiral auxiliaries(2 ) in asymmetric synthesis.(3 ) in particular , tetrahydroisoquinolines ( thiqs ) and indoles are common structural motifs in important compounds such as natural products(4 ) as well as pharmaceuticals(5 ) and display significant antitumor activities.(6 ) 1-arylated thiqs have been demonstrated to have interesting pharmacological properties,(7 ) including anti - hiv(8 ) and neuroprotective activity.(9 ) due to the broad application possibilities of these compounds , methods for their ever more efficient preparation are continuously sought after . in this respect , transition - metal - catalyzed cross - coupling reactions of various reactive functional groups have been developed as powerful methods for constructing c c bonds.(10 ) however , it would be even more desirable to use c  h bonds directly for c  c bond formation . such transformations are usually termed c  h activation reactions.(11 ) in the case of sp c h bonds adjacent to a nitrogen could be efficiently activated , and several protocols were reported.(12 ) such reactions display much better atom efficiency in comparison to traditional cross - coupling reactions , since prefunctionalization of building blocks for later c  c bond formation can be avoided . h bonds of two substrates to be coupled directly with each other for c  c bond formation . this was realized in cross dehydrogenative coupling ( cdc ) reactions , which are defined as the cross - coupling of two different c h bonds of pronucleophiles and proelectrophiles.(14 ) using thiq as substrate it was reported that n - arylated thiqs can be coupled to a series of nucleophiles , such as nacn , nitroalkanes , terminal alkynes , malonates , malononitriles , pyrroles , 2-naphthol , and phenylboronic acids , as well as morita  baylis  hillman ( mbh ) adducts . such reactions have been reported by murahashi et al.,(16 ) li et al.,(17 ) and others.(18 ) one inspiration for the research published within this contribution was a recent report by the group of li on the cdc between functionalized indoles and position 1 of n - arylated thiqs . the presence of tert - butyl hydroperoxide ( tbhp as a solution in decane ) as oxidant proved to be necessary , but no additional solvent was needed using copper(i ) bromide as catalyst.(19 ) however , there is one significant limitation of this protocol , the removal of the n - phenyl group , which would allow further functionalization of the thiq on its amine group . although the removal of phenyl from amines was reported , it required conditions which are only tolerated by a small set of organic compounds ( 100 equiv of li / nh3/thf/40 c , 3 h).(20 ) alternatively , the authors used the p - methoxyphenyl group ( pmp ) , which should be removable in principle ; however , using standard deprotection conditions(21 ) we were unable to deprotect the indolated thiqs . using a generally removable protecting group ( pg ) instead would open the possibility to perform further transformations after the initial c  c bond forming step . this would be highly desirable if a cheap and readily available catalyst could be used for the cdc reaction . copper catalysts are highly attractive , since they are significantly cheaper and environmentally more benign compared to noble metal catalysts such as pd , ru , and rh . an early example of a c  c bond forming process using cu catalysts was the ullmann coupling reaction.(22 ) in recent years copper catalysis has regained much attention and several interesting contributions have been reported.(23 ) an even more attractive metal for catalytic systems would be iron , since it is environmentally and economically superior to copper and there are already many literature reports where iron catalysts show promising properties in many synthetically valuable transformations . also , our group contributed to this field by disclosing an improved protocol for the direct indolation and methoxyarylation of protected thiqs and isochroman by employing cheap iron salts as catalysts.(25 ) even more importantly , removable protecting groups such as the boc group could be used instead of phenyl or pmp , and these were easily cleaved under very mild reaction conditions in most cases in quantitative yield . within this contribution , we report a method for the indolation , pyrrolation , and methoxyphenylation of thiqs and isochroman under copper catalysis in the absence of any protecting group on thiq . additionally , iron- and copper - catalyzed protocols for the transformations of protected thiqs and isochroman were investigated . initially , various protected thiqs were synthesized according to literature protocols to identify protected thiqs suitable for the proposed transformations . they were then submitted to standard indolation conditions(19 ) using copper(i ) bromide as catalyst and tbhp as oxidizing agent at 50 c . copper(i ) bromide was chosen , since indolation of n - phenyl - thiq was reported in the presence of this catalyst ( table 1 ) cu(no3)23h2o employed . the starting material carrying the boc protecting group ( 1h ) afforded the best product yield ( 79% , entry 15 ) , followed by ac - protected 1a ( 47% , entry 2 ) , cbz - protected 1e ( 41% , entry 10 ) , and benzyl - protected 1c ( bn , 36% , entry 6 ) . the benzoyl - protected substrate 1d ( bz , 10% , entry 8) was less efficient . in the case of piv - protected 1b ( 21% , entry 2 ) heterocyclic substituents such as 2-pyridinyl ( 1 g ) gave the indolated product in 44% yield ( entry 14 ) ; however , this group requires a two - step protocol for cleavage . only the tosyl pg ( substrate 1f ) seemed to be ineffective in this transformation ( entry 16 ) . in summary , the copper - catalyzed indolation is not limited to protective groups carrying a carbonyl function as was the case for our previously disclosed iron - catalyzed protocol.(25 ) since the boc group ( substrate 1h ) turned out to be the most suitable pg using copper(i ) bromide as catalyst , this substrate was selected for a subsequent round of parameter optimizations , starting with the catalyst species . interestingly , copper(ii ) nitrate ( entry 11 ) showed the best conversion ( 82% ) , closely followed by copper(ii ) acetate ( entry 18 ) and copper halide salts ( entries 1922 ) . in the case of copper(i ) iodide ( entry 19 ) significant byproduct formation ( oxidized thiq 4h and other unidentified byproduct , scheme 1 ) could be monitored by hplc , resulting in a decrease in conversion to the desired product , whereas cleaner conversions were achieved when employing copper(i ) chloride ( 74% , entry 21 ) or copper(ii ) fluoride ( 76% , entry 22 ) . such a benzylic oxidation was already reported in the literature under related conditions ( 82 c , excess tbhp , iron(iii ) chloride hexahydrate).(28 ) double substitution at the c3 and n1 positions of the indole with 1h was not observed , as was reported in a similar cdc reaction of n , n - dimethylanilines with indoles.(29 ) to confirm that copper(ii ) nitrate is the catalyst of choice in combination with boc as the best pg , the other protected thiqs were also submitted to the indolation process using copper(ii ) nitrate as catalyst . generally , all yields obtained with copper(ii ) nitrate were slightly higher in comparison to the corresponding transformation catalyzed by copper(i ) bromide , and again the best yield of the desired product ( 79% , entry 15 ) was obtained using 1h as starting material . cbz ( 1e , 60% , entry 10 ) , bn ( 1c , 60% , entry 5 ) , and 2-pyridinyl ( 1 g , 61% , entry 13 ) also performed well . with bz as the pg ( 1d ) , the yield could be significantly increased from 10% ( entry 8) to 40% ( entry 7 ) . again , tos - protected starting material 1f was not accepted in this transformation ( entry 11 ) . finally , the role of the oxidant was examined : tbhp without catalyst ( entry 28 ) or stoichiometric amounts of copper in absence of an oxidant failed to perform the reaction , independent of the oxidation state of the copper salt ( entries 23 and 24 ) . hence , it seems that the oxidizing agent is not only required to reoxidize the copper salt from copper(i ) to copper(ii ) in the catalytic cycle . this result supports the proposed mechanism of li et al . , which suggests that a peroxide is required as oxidant to convert copper to the oxy - copper species b2 , which then coordinates to the nitrogen of thiq and forms the iminium - type intermediate c2 by elimination of water , which is then attacked by a nucleophile to form the desired product ( scheme 2).(30 ) in contrast to the iron - catalyzed transformation , a carbonyl group adjacent to the nitrogen of the thiq is not mandatory for the copper - catalyzed reaction , indicating a complexation of the copper with the nitrogen to form species a2 rather than with the oxygen of the carbonyl group . in the copper(ii ) nitrate catalyzed transformation addition of tempo , a radical scavenger , did not result in a decrease in product formation , in contrast to our results when employing iron salts as catalysts.(25 ) this indicates that the product is formed by an ionic mechanism rather than through a radical pathway . other oxidants such as hydrogen peroxide ( entry 25 ) and mcpba ( entry 26 ) only showed traces of the desired product . thus , tbhp seems to be mandatory as the oxidant in this reaction . in scheme 2 the proposed mechanism for the iron- and copper catalyzed transformations after we established optimized reaction conditions , a set of various functionalized indoles was reacted with n - boc thiq . the results of the copper - catalyzed variant are compared with the results of our previously disclosed iron - catalyzed protocol in table 2 . conditions : ethylene glycol , 250 c , microwave , 30 s. yyield after deprotection of the boc pg ; np = not performed . it was found that , depending on the indole derivative applied , either iron or copper gave better results , whereas the latter metal was favored in most cases . simple indole ( table 2 , entry 1 ) gave good yields in both the copper- and iron - catalyzed processes ( 3h , 79% and 54% respectively ) . n - methylindole ( table 2 , entry 2 ) was also well tolerated by both catalysts ; however , copper performed slightly better than the iron catalyst ( 3i , 70% vs 65% yield ) . a significant difference in substrate conversion was observed when employing 2-methylindole : in the copper - catalyzed reaction the desired product 3j was obtained in 67% yield ( table 2 , entry 3 ) . this good yield is especially remarkable , since it shows that sterically hindered indoles can also be applied in this transformation ; this was not the case for the iron catalyst , where only 23% of 3j could be obtained . this result is in line with our proposed mechanism for the iron - catalyzed indolation process , where the iron species coordinates to the carbonyl group of the boc pg as well as to the nitrogen of the indole.(25 ) thus , complexation might be hindered due to the methyl group at position c-2 of indole , resulting in a decreased yield . on the other hand , a free amine functionality ( table 2 , entry 4 ) was not tolerated at all in copper catalysis and only 16% of 3k could be isolated when using iron(iii ) nitrate as catalyst . in copper catalysis both electron - withdrawing ( 3m  o ) and electron - donating ( 3l ) substituents are well tolerated at position c-5 of indole . substituents at positions 6 ( table 2 , entry 9 ) and 7 ( table 2 , entry 10 ) were also tolerated ( 3p , q ) . the picture completely changes when looking at the iron - catalyzed yields : with 5-nitro ( table 2 , entry 6 ) , 5-chloro ( table 2 , entry 8) , and 7-nitro substituents ( table 2 , entry 10 ) even better yields were obtained in comparison to the case for the copper - catalyzed reactions ( 3 m , 66% vs 59% ; 3o , 72% vs 66% ; 3q , 70% vs 46% ) . in these cases , the oxidized n - boc thiq byproduct 4h that always formed was formed to a lesser extent compared to the case for the copper - catalyzed protocol . since iron has a high affinity toward oxygen,(31 ) it was not surprising that the 5-methoxy - substituted product 3l was obtained in a notably lower yield ( table 2 , entry 5 ) , and the ester substituent ( table 2 , entry 7 ) was even less tolerated as a functional group ( 3n ) . in addition to indole , also other ring systems could be applied as coupling partners , such as 7-azaindole ( 3r , 42% and 44% ) and 6-chlorodeazapurine ( table 2 , entry 12 ) . in the case of 7-azaindole ( table 2 , entry 11 ) comparably mediocre yields were achieved with copper as well as with iron catalysis . using copper(ii ) on the other hand , the desired product was only observed in traces on tlc when using iron(iii ) nitrate . having established two protocols for the indolation of n - boc - thiq , we finally attempted to cleave the boc protecting group in order to obtain the free nh 1-indolated nh - thiqs . initially , standard acidic deprotection conditions(32 ) were used however decomposition of the starting material 3h was observed . only in refluxing acoh was a mediocre yield of 40% of 5h obtained , in addition to decomposition products . in the search for milder conditions we found that using tmscl in meoh at room temperature gave excellent results ( table 2).(33 ) in most cases quantitative yields of the deprotected products the deprotection in the presence of 6-cl - indole toward compound 5p gave the lowest but still satisfactory yield of 86% ( table 2 , entry 21 ) . a second alternative thermal deprotection of the boc group under microwave irradiation(34 ) would be an operationally simple alternative strategy to classical deprotection . it was found that starting materials 3h , i could be deprotected in excellent yield to afford 5h ( 89% , table 2 , entry 13 ) and 5i ( 97% , table 2 , entry 14 ) on heating to 250 c under microwave irradiation . this method proved to be very time efficient , since 30 s of hold time was sufficient for complete deprotection . unfortunately , in other cases decomposition of the starting materials was observed and the protocol was hence not generally applicable . overall , a three - step procedure for the synthesis of 1-indolated thiqs was developed which delivers high yields due to the high - yielding introduction and cleavage of a versatile protecting group . however , cdc of unprotected thiq and substituted indoles would represent an even more atom efficient transformation . in such a process , two reaction steps ( installation and cleavage of the protecting group ) could be circumvented , which also saves time and material resources otherwise needed for purification of the intermediate products . to our delight , indolation of thiq 6 toward products 5 could be achieved in good yields ( table 3 ) even without n - protection using copper(ii ) nitrate as catalyst . when standard conditions were applied for indolation from the above series of experiments on boc - protected precursors , thiq ( 1.0 equiv of indole , 0.8 equiv of thiq ) could be indolated in approximately 50% yield , independent of the functional group of the indole ( table 3 , entries 4 , 7 , 9 , 11 , 14 , 16 , and 17 ) . 3,4-dihydroisoquinoline ( dhiq ) was also formed as a byproduct via oxidative dehydrogenation to approximately the same extent as the desired products.(35 ) changing the ratio of substrates to 2 equiv of thiq and 1.0 equiv of indole resulted in an increased yield of the desired product 5h of 74% ( table 3 , entry 3 ) . a further improved yield of 5h of 85% ( table 3 , entry 2 ) was achieved when 4 equiv of 6 was employed . these results indicate that dhiq byproduct formation occurs at approximately the same reaction rate as the desired product formation . an even higher excess of thiq ( 8 equiv ) did not improve the yield further ( table 3 , entry 1 ) . also in other cases an excess of 2 equiv of thiq ( table 3 , entries 10 , 12 , and 18 ) gave better yields . it has to be pointed out , that 1-methyl- ( table 3 , entry 6 ) , 3-methyl- ( table 3 , entry 8) , and 7-nitroindoles ( table 3 , entry 15 ) are ineffective substrates in this particular transformation . the failure of 1-methylindole might indicate that a free indole nh group is mandatory for complexation with the copper catalyst and that this step is important for initiating the reaction . in the case of 3-methylindole , the c2 position of the indole is probably not sufficiently electron rich to undergo this type of transformation ( table 3 , entry 8) . on the other hand , 7-nitroindole competes with the free nh group for complexation with the copper - species , and therefore no desired product is formed.(36 ) reaction time : 2 days . also , iron catalysis was investigated for this transformation but did not give any indolated product . thus , protection of nitrogen with a carbonyl pg is mandatory for this metal , since only thiqs with a pg containing a carbonyl group showed successful indolation , due to coordination of the iron species with the oxygen of the carbonyl group.(25 ) on comparison of the two outlined methods , reaction of the unprotected thiq is superior with regard to atom efficiency , even though an excess of thiq is required in order to obtain high yields ( scheme 3 ) . the same is true regarding time efficiency , since two reaction steps can be avoided . still , the iron- and copper - catalyzed protocols can be useful alternatives in cases where the free nh of thiq is not tolerated . two such examples were encountered : i.e. , 1-methyl- ( table 2 , entry 2 ) and 7-nitroindole ( table 2 , entry 10 ) . in these cases the protocol employing fe(no3)3 as catalyst gave 57% and 63% yields over three steps and the cu(no3)2-catalyzed method gave 63% and 41% yields , respectively , again over three steps . generally , when the overall yield over three steps is compared to the yield of the direct protocol , higher yields are obtained in the direct method when 2 equiv of thiq is applied . when only 1 equiv of this substrate is used , the three - step protocol including protection and deprotection compares favorably . hence , it can be concluded that all three protocols ( copper - catalyzed indolation of unprotected thiq , copper - catalyzed indolation of n - protected thiq , and iron - catalyzed indolation of n - protected thiq ) can be of value , depending on the synthetic problem . the protection deprotection pathway might be of special value when more elaborate and , hence , more expensive thiq derivatives are used as substrates . after we established the principal reactivity on indole , it was further investigated whether pyrroles can also undergo a cdc with thiq . thus , pyrrole 7a was reacted with 2 equiv of thiq 6 , which afforded the desired product 8a in 44% yield ( scheme 4 ) . the new carbon  carbon bond was formed in this case between c1 of thiq and c2 of pyrrole , so again the more electron rich position of the pronucleophile reacts . conditions : cu(no3)23h2o ( 5 mol % ) , tbhp ( 1.3 equiv ) , 50 c , 15 h. the yield dropped dramatically when the pyrrolation was performed on boc - protected 1h : only traces of the desired product 8d were observed employing copper catalysis and only 11% of the desired product could be isolated in the iron - catalyzed reaction ( see the supporting information ) . thus , the scope of the pyrrolation was investigated on 6 : also 4,5,6,7-tetrahydroindole gave the desired product in 41% yield . electron - poor pyrroles such as 2-acetylpyrrole did not show any conversion according to gc / ms . notably , also 1-methylpyrrole was ineffective , which is in line with results obtained for 1-methylindole ( table 3 , entry 6 ) ; we understand this as further evidence of the importance of a free nh group in the pronucleophile . interestingly , the reaction was also successful when using 2,5-dimethylpyrrole 7b as substrate , this time leading to c  c bond formation at c3 of pyrrole , affording product 8b on the basis of the above results , we became interested in extending the substrate scope of the transformation to other coupling partners in addition to ( aza)indoles and pyrroles . since the pronucleophile needs to be electron rich , high electron density arenes were submitted to the reaction conditions with thiqs . gratifyingly , boc - protected 1h ( table 4 , entry 1 ) , bz - protected 1d ( table 4 , entry 2 ) , and cbz - protected 1e ( table 4 , entry 3 ) were found to be suitable substrates for methoxyarylation with 1,3,5-trimethoxybenzene . in marked contrast to the indolation reactions , unprotected thiq 6 , bn - protected 1c ( table 4 , entry 4 ) and pmp - protected thiq ( table 4 , entry 5 ) were inefficient under both copper and iron catalysis . the best yield in this methoxyarylation reaction was obtained using 1,3,5-trimethoxybenzene as the most electron rich aryl coupling partner and boc - protected 1h as substrate , where a good yield of 81% in iron catalysis and 76% ( table 4 , entry 1 ) in copper catalysis was obtained . decreasing the electron density on the aryl coupling partner as in 1,3-dimethoxybenzene also showed product formation of 10f but , as could be expected , with a lower yield of 34% ( copper ) and 41% ( iron ) ( table 4 , entry 9 ) . also , a less favorable arrangement of three methoxy groups led to decreased product yield : 1,2,4-trimethoxybenzene led to 47% ( table 4 , entry 7 , fe ) and 23% ( table 4 , entry 7 , cu ) 10d , respectively . it has to be noted that only arylation product deriving from a reaction at position 5 of 1,2,4-trimethoxybenzene was observed . principally , position 3 would be activated to a similar extent but is sterically less favored . the presence of four methoxy groups in the aryl coupling partner gave , especially in the cu - catalyzed protocol , again a higher yield ( 10e , table 4 , entry 8) . next , we investigated possible extensions to other proelectrophiles ; therefore , isochroman 9 was tested as the starting material as well ( table 4 , entries 1013 ) . attempts to use 9 as starting material for indolations unfortunately failed , leading rather to bis - indolation via c  h bond oxidation and c  o cleavage , which is in line with recent reports by li et al.(37 ) however , 1,3,5-trimethoxybenzene also reacted with 9 as coupling partner to afford the desired product 11a in 55% and 51% yields , respectively ( table 4 , entry 10 ) . this confirms that this arylation reaction is not limited to thiq but also isochroman can be used as substrate ; however , lower yields were obtained for both metal catalysts in comparison to the case for thiq substrates . still , this is an interesting extension to existing protocols , since it demonstrates that the transformation is limited neither to thiq starting materials nor to indole or pyrrole coupling partners , consequently broadening the substrate scope considerably . comparable less electron rich 1,3-dimethoxybenzene also showed product formation , but again with lower yields of 12% ( 11c , entry 12 , fe ) and 23% ( 11c , entry 12 , cu ) . with regard to 1,2,4-trimethoxybenzene ( 11d , entry 13 ) and 1,2,3,5-tetramethoxybenzene ( 11b , entry 11 ) the same trends in yield were observed as for the corresponding reactions on thiq 1h . for both starting materials 1h and 9 anisole in summary , an alternative copper- and iron - catalyzed method for the indolation , pyrrolation , and methoxyphenylation of thiqs and for the methoxyphenylation of isochroman was developed . most importantly , cleavable n - protecting groups can be applied using the outlined protocols , which represents a significant extension of this methodology in comparison to previous reports . the boc group can be removed under mild conditions with tmscl or within seconds in excellent yield using high - temperature microwave conditions . it could be demonstrated that unprotected thiq could be directly functionalized with indoles and pyrroles in a copper - catalyzed reaction . general notes and instrumentation are provided in the supporting information . protected thiqs and 4,5,6,7-tetrahydro-1h - indole were synthesized according to literature procedures.(26 ) a mixture of protected thiq ( 0.857 mmol , 1.0 equiv ) , catalyst ( cu(no3)23h2o , 10.4 mg ; fe(no3)39h2o , 17.3 mg ; 42.9 mol , 0.05 equiv ) , and indole ( 1.03 mmol , 1.2 equiv ) was placed into a 5 ml glass vial in air . tbhp ( 203 l , 5.5 m in decane , 1.3 equiv ) was added dropwise at 0 c in air , and the dark greenish slurry was stirred for 10 min at 0 c . the neat mixture was then slowly heated to 50 c , whereupon the color changed to dark brown , and stirring was continued for 15 h in a heating block . the dark brown slurry was diluted with dcm ( 3 ml ) and directly subjected to flash column chromatography ( 100 g of sio2 ) , applying the solvent mixture used for tlc . yield for cu 134 mg ( 54% ) and for fe traces ; pale yellow solid ; mp 208211 c ; tlc rf ( pe / etoac 1/1 ) = 0.18 ; gc / ms ( ei+ ) m / z ( rel intensity ) 290 ( m , 50 ) , 273 ( 14 ) , 248 ( 18 ) , 247 ( 100 ) , 232 ( 29 ) , 230 ( 14 ) , 218 ( 28 ) , 217 ( 28 ) , 132 ( 16 ) , 131 ( 24 ) , 130 ( 50 ) , 117 ( 25 ) , 115 ( 27 ) , 103 ( 21 ) , 89 ( 12 ) , 77 ( 12 ) ; h nmr ( 200 mhz , dmso- d6 ) mixture of rotamers 1:0.17 ,  2.10 ( s , 3h ) , 2.25 ( s , 0.51h ) , 2.742.90 ( m , 1.30h ) , 3.02 ( ddd , j = 17.2 hz , j = 11.6 hz , j = 5.8 hz , 1h ) , 3.243.45 ( m , 1.30h ) , 3.77 ( dd , j = 13.7 hz , j = 5.4 hz , 1h ) , 4.26 ( bs , 0.16h ) , 6.40 ( bs , 0.17h ) , 6.58 ( d , j = 2.0 hz , 1h ) , 6.897.27 ( m , 8h ) , 7.34 ( d , j = 7.9 hz , 1.35h ) , 7.57 ( d , j = 7.8 hz , 1h ) , 10.93 ( s , 1h ) , 11.10 ( s , 0.17h ) ; c nmr ( 50 mhz , dmso - d6 ) : mixture of rotamers 1:0.17 ,  21.4 ( q ) , 28.4 ( t ) , 39.1 ( t , overlap with dmso signal ) , 47.9 ( d ) , 111.4 ( d ) , 117.1 ( s ) , 118.7 ( d ) , 119.2 ( d ) , 121.3 ( d ) , 125.4 ( d ) , 125.7 ( d ) , 126.1 ( s ) , 126.5 ( d ) , 128.2 ( d ) , 128.8 ( d ) , 134.4 ( s ) , 136.2 ( s ) , 136.3 ( s ) , 167.7 ( s ) . yield for cu 73 mg ( 26% ) and for fe traces ; off white powder ; mp 184186 c ; tlc rf ( pe / etoac 2/1 ) = 0.27 ; gc / ms ( ei+ ) m / z ( rel intensity ) 332 ( m , 27 ) , 248 ( 19 ) , 247 ( 100 ) , 232 ( 35 ) , 231 ( 14 ) , 218 ( 25 ) , 217 ( 23 ) , 144 ( 11 ) , 132 ( 26 ) , 130 ( 28 ) , 117 ( 10 ) , 115 ( 17 ) , 57 ( 24 ) ; h nmr ( 200 mhz , cdcl3 )  1.24 ( s , 9h ) , 2.73 ( ddd , j = 16.4 hz , j = 4.1 hz , j = 0.9 hz , 1h ) , 3.04 ( ddd , j = 17.0 hz , j = 12.4 hz , j = 6.1 hz , 1h ) , 3.44 ( ddd , j = 13.9 hz , j = 12.6 hz , j = 4.2 hz , 1h ) , 4.05 ( ddd , j = 13.6 hz , j = 6.2 hz , j = 1.4 hz , 1h ) , 6.56 ( d , j = 2.3 hz , 1h ) , 6.97 ( ddd , j = 8.0 hz , j = 7.1 hz , j = 1.1 hz , 1h ) , 7.047.16 ( m , 5h ) , 7.167.21 ( m , 1h ) , 7.25 ( d , j = 8.0 hz , 1h ) , 7.50 ( d , j = 7.9 hz , 1h ) , 8.06 ( s , 1h ) ; c nmr ( 50 mhz , cdcl3 )  28.4 ( 3c , q ) , 29.2 ( t ) , 39.1 ( s ) , 39.6 ( t ) , 50.4 ( d ) , 110.9 ( d ) , 119.1 ( s ) , 119.8 ( d ) , 120.4 ( d ) , 122.2 ( d ) , 125.6 ( d ) , 125.9 ( d ) , 126.4 ( s ) , 126.6 ( d ) , 128.6 ( d ) , 128.7 ( d ) , 133.7 ( s ) , 136.4 ( s ) , 136.5 ( s ) , 175.7 ( s ) . yield for cu 181 mg ( 60% ) and for fe 20 mg ( 7% ) ; pale yellow solid ; mp 5560 c ; tlc rf ( pe / et2o 1/1 ) = 0.45 ; gc / ms ( ei+ ) m / z ( rel intensity ) 338 ( m+ , 75 ) , 337 ( 56 ) , 247 ( 32 ) , 245 ( 16 ) , 231 ( 22 ) , 219 ( 50 ) , 218 ( 100 ) , 217 ( 35 ) , 130 ( 11 ) , 106 ( 15 ) , 91 ( 31 ) ; hrms ( esi+ ) : exact mass calculated for c24h22n2 339.1856 , found : 339.1852 [ m + h ] ; h nmr ( 200 mhz , dmso - d6 )  2.322.47 ( m , 1h ) , 2.702.88 ( m , 1h ) , 2.923.12 ( m , 2h ) , 3.26 ( d , j = 13.7 hz , 1h ) , 3.81 ( d , j = 13.7 hz , 1h ) , 4.88 ( s , 1h ) , 6.757.39 ( m , 13h ) , 7.45 ( d , j = 7.8 hz , 1h ) , 10.97 ( s , 1h ) ; c nmr ( 50 mhz , apt , dmso - d6 )  28.8 ( t ) , 47.1 ( t ) , 58.2 ( t ) , 61.2 ( d ) , 111.4 ( d ) , 116.4 ( s ) , 118.2 ( d ) , 120.2 ( d ) , 120.9 ( d ) , 125.3 ( d ) , 125.49 ( d ) , 125.53 ( d ) , 125.9 ( s ) , 126.5 ( d ) , 127.9 ( d ) , 128.0 ( d , 2c ) , 128.1 ( d ) , 128.4 ( d , 2c ) , 134.3 ( s ) , 136.9 ( s ) , 138.7 ( s ) , 139.6 ( s ) . yield for cu 120 mg ( 40% ) and for fe 67 mg ( 22% ) ; brown solid ; mp 226228 c ; tlc rf ( pe / etoac 2/1 ) = 0.29 ; gc / ms ( ei+ ) m / z ( rel intensity ) 352 ( m , 40 ) , 248 ( 20 ) , 247 ( 100 ) , 232 ( 32 ) , 218 ( 21 ) , 217 ( 21 ) , 130 ( 18 ) , 115 ( 12 ) , 105 ( 56 ) , 77 ( 44 ) ; hrms ( esi ) exact mass calculated for c24h20n2o 353.1648 , found 353.1639 [ m + h ] ; h nmr ( 400 mhz , cdcl3 )  2.75 ( d , j = 14.6 hz , 1h ) , 2.973.11 ( m , 1h ) , 3.47 ( dt , j = 13.4 hz , j = 3.3 hz , 1h ) , 3.66 ( dd , j = 13.2 hz , j = 5.7 hz , 1h ) , 6.68 ( s , 1h ) , 7.13 ( t , j = 7.3 hz , 1h ) , 7.187.54 ( m , 12h ) , 7.85 ( d , j = 7.6 hz , 1h ) , 8.34 ( bs , 1h ) ; h nmr ( 200 mhz , dmso - d6 )  2.75 ( d , j = 16.0 hz , 1h ) , 2.863.10 ( m , 1h ) , 3.203.60 ( m , 2h ) , 6.64 ( bs , 1h ) , 6.897.51 ( m , 13h ) , 7.65 ( d , j = 7.9 hz , 1h ) , 11.03 ( s , 1h ) ; c nmr ( 101 mhz , cdcl3 )  29.5 ( t ) , 40.6 ( t ) , 49.0 ( d ) , 111.1 ( d ) , 118.6 ( s ) , 120.0 ( d ) , 120.3 ( d ) , 122.3 ( d ) , 125.7 ( d ) , 126.1 ( d ) , 126.4 ( 2d ) , 126.9 ( d ) , 127.3 ( s ) , 128.5 ( 4c , d ) , 128.8 ( d ) , 128.9 ( d ) , 129.4 ( d ) , 133.8 ( s ) , 135.7 ( s ) , 136.4 ( s ) , 136.6 ( s ) , 169.9 ( s ) ; c nmr ( 50 mhz , apt , dmso - d6 )  28.6 ( t ) , ( ch2 group at 40.6 ppm in cdcl3 overlaps with dmso signal ) , 48.4 ( d ) , 111.6 ( d ) , 116.8 ( s ) , 118.9 ( d ) , 119.0 ( d ) , 121.4 ( d ) , 125.8 ( d ) , 125.9 ( s ) , 126.1 ( d ) , 126.8 ( d ) , 128.2 ( d ) , 128.5 ( 4c , d ) , 128.9 ( d ) , 129.3 ( d ) , 134.0 ( s ) , 135.6 ( s ) , 136.4 ( 2c overlapping , s ) , 168.6 ( s ) . yield for cu 171 mg ( 60% ) and for fe 135 mg ( 41% ) ; white powder ; mp 6264 c ; tlc rf ( pe / etoac 5/1 ) = 0.55 ; gc / ms ( ei+ ) m / z ( rel intensity ) 382 ( m , 3 ) , 292 ( 7 ) , 291 ( 40 ) , 248 ( 20 ) , 247 ( 100 ) , 218 ( 8) , 217 ( 7 ) , 130 ( 12 ) , 103 ( 5 ) , 91 ( 6 ) ; hrms ( esi ) exact mass calculated for c25h22n2o2 383.1754 , found 383.1722 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  2.73 ( dd , 1h , j = 16.7 hz , j = 2.7 hz , 1h ) , 2.903.36 ( m , 2h ) , 3.804.30 ( m , 1h ) , 5.105.46 ( m , 2h ) , 6.486.84 ( m , 2h ) , 6.887.82 ( m , 13h ) , 8.19 ( bs , 1h ) ; c nmr ( 50 mhz , apt , cdcl3 )  28.6 ( t ) , 37.4 ( t ) , 51.5 ( d ) , 67.1 ( t ) , 111.0 ( d ) , 118.5 ( s ) , 119.8 ( d ) , 120.2 ( d ) , 122.2 ( d ) , 125.0 ( d ) , 125.8 ( d , 2c ) , 126.4 ( s ) , 126.7 ( d ) , 127.7 ( d ) , 128.0 ( d ) , 128.4 ( d ) , 128.5 ( d , 2c ) , 129.0 ( d ) , 134.6 ( s ) , 136.0 ( s ) , 136.3 ( s ) , 136.7 ( s ) , 154.9 ( s ) . yield for cu 171 mg ( 61% ) ; pale yellow powder ; mp 177178 c ; tlc rf ( pe / etoac 2/1 ) = 0.51 ; gc / ms ( ei+ ) m / z ( rel intensity ) 325 ( m 40 ) , 248 ( 19 ) , 247 ( 100 ) , 232 ( 24 ) , 230 ( 15 ) , 218 ( 24 ) , 217 ( 27 ) , 195 ( 12 ) , 130 ( 17 ) , 117 ( 14 ) , 115 ( 15 ) ; hrms ( esi ) exact mass calculated for c22h19n3 326.1652 , found 326.1652 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  2.80 ( dt , j = 16.1 hz , j = 3.9 hz , 1h ) , 3.12 ( ddd , j = 16.3 hz , j = 10.7 hz , j = 5.6 hz , 1h ) , 3.63 ( ddd , j = 13.6 hz , j = 10.7 hz , j = 4.4 hz , 1h ) , 3.98 ( td , j = 13.6 hz , j = 4.3 hz , 1h ) , 6.58 ( dd , j = 7.0 hz , j = 5.0 hz , 1h ) , 6.65 ( d , j = 2.2 hz , 1h ) , 6.76 ( d , j = 8.6 hz , 1h ) , 7.04 ( t , j = 7.1 hz , 1h ) , 7.107.23 ( m , 5h ) , 7.277.35 ( m , 2h ) , 7.47 ( ddd , j = 8.8 hz , j = 7.2 hz , j = 2.0 hz , 1h ) , 7.70 ( d , j = 7.8 hz , 1h ) , 8.06 ( s , 1h ) , 8.28 ( dd , j = 4.9 hz , j = 1.9 hz , 1h ) ; c nmr ( 50 mhz , apt , cdcl3 )  26.9 ( t ) , 38.9 ( t ) , 52.2 ( d ) , 106.5 ( d ) , 111.0 ( d ) , 112.0 ( d ) , 119.2 ( s ) , 119.5 ( d ) , 120.1 ( d ) , 122.0 ( d ) , 124.4 ( d ) , 125.6 ( d ) , 126.5 ( d ) , 126.6 ( s ) , 128.3 ( d ) , 128.8 ( d ) , 135.4 ( s ) , 136.5 ( s ) , 137.4 ( s ) , 137.5 ( d ) , 148.1 ( d ) , 157.9 ( s ) . yield for cu 235 mg ( 79% ) and for fe 160 mg ( 54% ) ; off white powder ; mp 137139 c ; tlc rf ( pe / et2o 2/1 ) = 0.18 ; gc / ms ( ei+ ) m / z ( rel intensity ) 248 ( 46 ) , 247 ( 91 ) , 245 ( 100 ) , 230 ( 18 ) , 218 ( 53 ) , 130 ( 52 ) , 121 ( 46 ) , 117 ( 38 ) , 108 ( 50 ) , 103 ( 21 ) ; hrms ( esi ) exact mass calculated for c22h24n2o2 371.1735 . found 371.1730 [ m + na ] ; h nmr ( 400 mhz , dmso - d6 )  1.46 ( s , 9h ) , 2.77 ( d , j = 15.8 hz , 1h ) , 2.842.96 ( m , 1h ) , 3.07 ( dt , j = 12.8 hz , j = 4.3 hz , 1h ) , 3.94 ( bs , 1h ) , 6.376.85 ( m , 2h ) , 6.96 ( t , j = 7.4 hz , 1h ) , 7.08 ( t , j = 7.6 hz , 1h ) , 7.15 ( bs , 2h ) , 7.22 ( d , j = 3.1 hz , 2h ) , 7.36 ( d , j = 8.1 hz , 1h ) , 7.58 ( bs , 1h ) , 10.95 ( s , 1h ) ; h nmr ( 200 mhz , cdcl3 )  1.55 ( s , 9h ) , 2.632.85 ( m , 1h ) , 2.923.27 ( m , 1h ) , 4.05 ( bs , 1h ) , 6.60 ( bs , 1h ) , 6.75 ( bs , 1h ) , 7.067.25 ( m , 6h ) , 7.35 ( d , j = 7.7 hz , 1h ) , 7.80 ( bs , 1h ) , 8.14 ( bs , 1h ) ; c nmr ( 50 mhz , apt , cdcl3 )  28.4 ( 3c , q ) , 28.5 ( t ) , 37.6 ( t ) , 50.5 ( d ) , 79.7 ( s ) , 111.1 ( d ) , 118.6 ( s ) , 119.5 ( d ) , 119.9 ( d ) , 122.0 ( d ) , 125.0 ( d ) , 125.6 ( d ) , 126.4 ( s ) , 126.5 ( d ) , 128.3 ( s ) , 128.3 ( d ) , 129.0 ( d ) , 134.8 ( s ) , 136.3 ( s ) , 136.4 ( s ) , 154.3 ( s ) . yield for cu 218 mg ( 70% ) and for fe 203 mg ( 65% ) ; white powder ; mp 7072 c ; tlc rf ( pe / etoac 3/1 ) = 0.78 ; gc / ms ( ei+ ) m / z ( rel intensity ) 262 ( 48 ) , 261 ( 100 ) , 259 ( 33 ) , 245 ( 12 ) , 232 ( 22 ) , 217 ( 20 ) , 157 ( 6 ) , 130 ( 22 ) , 103 ( 7 ) , 77 ( 5 ) ; hrms ( esi ) exact mass calculated for c23h26n2o2 363.2067 , found 363.2072 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  1.58 ( s , 9h ) , 2.682.88 ( m , 1h ) , 2.963.30 ( m , 2h ) , 3.70 ( s , 3h ) , 3.884.32 ( m , 1h ) , 6.49 ( s , 1h ) , 6.74 ( bs , 1h ) , 7.087.36 ( m , 7h ) , 7.82 ( bs , 1h ) ; c nmr ( 50 mhz , apt , cdcl3 )  28.4 ( t ) , 28.6 ( 3c , q ) , 32.6 ( q ) , 37.5 ( t ) , 50.4 ( d ) , 79.5 ( s ) , 109.1 ( d ) , 117.4 ( s ) , 119.2 ( d ) , 120.4 ( d ) , 121.8 ( d ) , 125.6 ( d ) , 126.5 ( d ) , 127.0 ( s ) , 128.4 ( d ) , 129.0 ( d ) , 129.4 ( d ) , 135.0 ( s ) , 136.5 ( s ) , 137.1 ( s ) , 154.2 ( s ) . yield for cu 209 mg ( 67% ) and for fe 72 mg ( 23% ) ; pale yellow powder ; mp 8184 c ; tlc rf ( pe / etoac 2/1 ) = 0.69 ; gc / ms ( ei+ ) m / z ( rel intensity ) 262 ( 62 ) , 261 ( 100 ) , 245 ( 61 ) , 244 ( 37 ) , 219 ( 21 ) , 218 ( 44 ) , 131 ( 34 ) , 130 ( 85 ) , 103 ( 18 ) , 77 ( 20 ) ; hrms ( esi ) exact mass calculated for c23h26n2o2 385.1886 , found 385.1896 [ m + na ] ; h nmr ( 200 mhz , cdcl3 )  1.49 ( s , 9h ) , 2.24 ( s , 3h ) , 2.78 ( dd , j = 16.7 hz , j = 3.0 hz , 1h ) , 3.003.80 ( m , 2h ) , 4.14 ( dd , j = 11.8 hz , j = 3.5 hz , 1h ) , 6.66 ( s , 1h ) , 6.836.94 ( m , 1h ) , 6.987.13 ( m , 4h ) , 7.177.26 ( m , 3h ) , 7.91 ( bs , 1h ) ; h nmr ( 200 mhz , dmso - d6 )  1.44 ( s , 9h ) , 2.19 ( s , 3h ) , 2.743.28 ( m , 3h ) , 4.01 ( dd , j = 13.3 hz , j = 3.3 hz , 1h ) , 6.50 ( s , 1h ) , 6.676.78 ( m , 1h ) , 6.817.02 ( m , 3h ) , 7.057.15 ( m , 1h ) , 7.157.28 ( m , 3h ) , 10.95 ( s , 1h ) ; c nmr ( 50 mhz , apt , cdcl3 )  12.6 ( q ) , 28.5 ( 3c , q ) , 28.6 ( t ) , 38.3 ( t ) , 51.0 ( d ) , 79.7 ( s ) , 110.1 ( d ) , 113.3 ( s ) , 119.3 ( d ) , 119.5 ( d ) , 120.9 ( d ) , 126.3 ( d ) , 126.5 ( d ) , 128.3 ( d ) , 128.5 ( s ) , 129.0 ( d ) , 133.9 ( s ) , 134.9 ( s ) , 134.9 ( s ) , 137.0 ( s ) , 154.2 ( s ) ; c nmr ( 50 mhz , apt , dmso - d6 )  11.9 ( q ) , 27.9 ( t ) , 28.0 ( 3c , q ) , 37.8 ( t ) , 50.3 ( d ) , 78.9 ( s ) , 110.4 ( d ) , 111.6 ( s ) , 118.1 ( d ) , 118.4 ( d ) , 119.9 ( d ) , 126.0 ( d ) , 126.4 ( d ) , 127.7 ( s ) , 127.8 ( d ) , 128.8 ( d ) , 134.2 ( s ) , 134.4 ( s ) , 134.8 ( s ) , 136.7 ( s ) , 153.3 ( s ) . yield for cu no conversion and for fe 50 mg ( 16% ) ; dark brown solid ; mp 9698 c ; tlc rf ( pe / et2o 1/1 ) = 0.31 ; gc / ms ( ei+ ) m / z ( rel intensity ) 263 ( 48 ) , 262 ( 30 ) , 258 ( 40 ) , 246 ( 75 ) , 245 ( 100 ) , 233 ( 13 ) , 218 ( 17 ) , 132 ( 23 ) , 130 ( 20 ) ; hrms ( esi ) exact mass calculated for c22h25n3o2 386.1839 , found 386.1854 [ m + na ] ; h nmr ( 400 mhz , cdcl3 )  1.48 ( s , 9h ) , 2.82 ( dd , j = 16.4 hz , j = 2.9 hz , 1h ) , 3.093.22 ( m , 1h ) , 3.41 ( dt , j = 13.3 hz , j = 3.6 hz , 1h ) , 4.07 ( dd , j = 13.6 hz , j = 5.7 hz , 1h ) , 6.66 ( s , 1h ) , 5.13 ( s , 1h ) , 6.68 ( d , j = 8.6 hz , 1h ) , 6.78 ( t , j = 2.7 hz , 1h ) , 7.03 ( d , j = 7.7 hz , 1h ) , 7.10 ( t , j = 7.3 hz , 1h ) , 7.14 ( d , j = 8.6 hz , 1h ) , 7.197.24 ( m , 2h ) , 7.86 ( s , 1h ) , nh2 group gives a broad signal between 2 and 5 ppm ; c nmr ( 101 mhz , apt , cdcl3 )  28.4 ( q , 3c ) , 28.5 ( t ) , 39.2 ( t ) , 53.8 ( d ) , 80.2 ( s ) , 101.3 ( d ) , 111.7 ( d ) , 113.8 ( d ) , 116.0 ( s ) , 123.7 ( d ) , 126.3 ( d ) , 126.5 ( d ) , 128.4 ( s ) , 128.9 ( d ) , 128.9 ( d ) , 130.8 ( s ) , 134.8 ( s ) , 137.4 ( s ) , 139.9 ( s ) , 155.5 ( s ) . yield for cu 174 mg ( 52% ) and for fe 140 mg ( 43% ) ; off - white powder ; mp 6972 c ; tlc rf ( pe / etoac 5/1 ) = 0.27 ; gc / ms ( ei+ ) m / z ( rel intensity ) 278 ( 59 ) , 277 ( 100 ) , 261 ( 53 ) , 249 ( 22 ) , 248 ( 24 ) , 233 ( 12 ) , 218 ( 10 ) , 204 ( 10 ) , 132 ( 10 ) , 130 ( 14 ) ; hrms ( esi ) exact mass calculated for c23h26n2o3 401.1836 , found 401.1822 [ m + na ] ; h nmr ( 200 mhz , dmso - d6 )  1.46 ( s , 9h ) , 2.633.19 ( m , 3h ) , 3.69 ( s , 3h ) , 3.88 ( bs , 1h ) , 6.52 ( bs , 2h ) , 6.73 ( dd , j = 8.8 hz , j = 2.1 hz , 1h ) , 7.017.32 ( m , 6h ) , 10.78 ( s , 1h ) ; c nmr ( 50 mhz , apt , dmso - d6 )  27.8 ( t ) , 28.0 ( 3c , q ) , 37.0 ( t ) , 50.1 ( d ) , 55.0 ( q ) , 78.8 ( s ) , 100.7 ( d ) , 111.5 ( d ) , 112.2 ( d ) , 116.8 ( s ) , 125.6 ( d ) , 126.4 ( s ) , 126.5 ( d ) , 127.9 ( d ) , 128.9 ( d ) , 131.4 ( s ) , 134.4 ( s ) , 136.0 ( s ) , 153.1 ( s ) , 153.4 ( s ) . yield for cu 200 mg ( 59% ) and for fe 222 mg ( 66% ) ; bright yellow solid ; mp 219221 c ; tlc rf ( pe / etoac 3/1 ) = 0.22 ; gc / ms ( ei+ ) m / z ( rel intensity ) 393 ( 43 ) , 292 ( 100 ) , 276 ( 10 ) , 263 ( 24 ) , 246 ( 34 ) , 217 ( 30 ) , 189 ( 8) , 146 ( 6 ) , 132 ( 6 ) , 130 ( 12 ) ; hrms ( esi ) exact mass calculated for c22h23n3o4 416.1581 , found 416.1589 [ m + na ] ; h nmr ( 200 mhz , dmso - d6 )  1.50 ( s , 9h ) , 2.633.07 ( m , 3h ) , 3.764.09 ( m , 1h ) , 6.62 ( s , 1h ) , 6.80 ( s , 1h ) , 7.097.29 ( m , 4h ) , 7.55 ( d , j = 9.0 hz , 1h ) , 8.02 ( dd , j = 9.0 hz , j = 2.2 hz , 1h ) , 8.73 ( s , 1h ) , 11.5011.86 ( m , 1h ) ; c nmr ( 50 mhz , apt , dmso - d6 )  27.7 ( t ) , 27.9 ( q , 3c ) , 37.0 ( t ) , 49.9 ( d ) , 79.5 ( s ) , 112.1 ( d ) , 116.4 ( d ) , 116.8 ( d ) , 119.9 ( s ) , 125.3 ( s ) , 125.7 ( d ) , 126.8 ( d ) , 128.0 ( d ) , 128.9 ( d ) , 129.0 ( d ) , 134.5 ( s ) , 135.1 ( s ) , 139.6 ( s ) , 140.6 ( s ) , 153.3 ( s ) . yield for cu 175 mg ( 50% ) and for fe 17 mg ( 5% ) ; pale yellow powder ; mp 221224 c ; tlc rf ( pe / et2o 1/1 ) = 0.18 ; gc / ms ( ei+ ) m / z ( rel intensity ) 306 ( 45 ) , 305 ( 100 ) , 289 ( 12 ) , 276 ( 18 ) , 247 ( 8) , 244 ( 8) , 217 ( 15 ) , 189 ( 6 ) , 144 ( 8) , 130 ( 16 ) ; hrms ( esi ) exact mass calculated for c24h26n2o4 429.1785 , found 429.1771 [ m + na ] ; h nmr ( 200 mhz , cdcl3 )  1.62 ( s , 9h ) , 2.602.83 ( m , 1h ) , 2.903.18 ( m , 2h ) , 3.90 ( s , 3h ) , 3.934.27 ( m , 1h ) , 6.58 ( d , j = 1.9 hz , 1h ) , 6.616.89 ( m , 1h ) , 7.087.24 ( m , 4h ) , 7.34 ( d , j = 8.6 hz , 1h ) , 7.91 ( dd , j = 8.6 hz , j = 1.2 hz , 1h ) , 8.58 ( bs , 1h ) ; 8.63 ( s , 1h ) , h nmr ( 200 mhz , dmso - d6 )  1.52 ( s , 9h ) , 2.643.10 ( m , 3h ) , 3.82 ( s , 3h ) , 3.90 ( bs , 1h ) , 6.58 ( bs , 1h ) , 6.63 ( bs , 1h ) , 7.077.30 ( m , 4h ) , 7.45 ( d , j = 8.6 hz , 1h ) , 7.75 ( d , j = 8.6 hz , 1h ) , 8.49 ( s , 1h ) , 11.34 ( s , 1h ) ; c nmr ( 50 mhz , apt , dmso - d6 )  27.6 ( t ) , 27.9 ( 3c , q ) , ( ch2 group at 36.2 ppm in cdcl3 overlaps with dmso signal ) , 50.4 ( d ) , 51.4 ( q ) , 79.5 ( s ) , 111.5 ( d ) , 118.6 ( s ) , 120.3 ( s ) , 121.9 ( d ) , 122.4 ( d ) , 125.57 ( s ) , 125.61 ( d ) , 126.7 ( d ) , 127.0 ( d ) , 127.9 ( d ) , 129.1 ( d ) , 134.5 ( s ) , 135.6 ( s ) , 139.0 ( s ) , 153.4 ( s ) , 167.1 ( s ) ; c nmr ( 50 mhz , apt , cdcl3 )  28.1 ( t ) , 28.4 ( q , 3c ) , 36.2 ( t ) , 51.2 ( d ) , 51.6 ( q ) , 80.7 ( s ) , 111.0 ( d ) , 120.1 ( s ) , 121.5 ( s ) , 122.7 ( d ) , 123.7 ( d ) , 125.6 ( d ) , 126.0 ( s ) , 126.4 ( d ) , 126.8 ( d ) , 128.2 ( d ) , 129.1 ( d ) , 134.9 ( s ) , 135.8 ( s ) , 139.2 ( s ) , 154.2 ( s ) , 168.2 ( s ) . yield for cu 215 mg ( 66% ) and for fe 236 mg ( 72% ) ; pale pink powder ; mp 202204 c ; tlc rf ( pe / etoac 3/1 ) = 0.56 ; gc / ms ( ei+ ) m / z ( rel intensity ) 284 ( 13 ) , 283 ( 38 ) , 282 ( 42 ) , 281 ( 100 ) , 279 ( 14 ) , 265 ( 9 ) , 253 ( 21 ) , 252 ( 22 ) , 217 ( 30 ) , 216 ( 11 ) , 164 ( 8) , 130 ( 26 ) , 103 ( 9 ) ; hrms ( esi ) : exact mass calculated for c22h23n2o2cl 405.1340 ; found 405.1350 [ m + na ] ; h nmr ( 200 mhz , dmso - d6 )  1.49 ( s , 9h ) , 2.653.09 ( m , 3h ) , 3.91 ( bs , 1h ) , 6.50 ( s , 1h ) , 6.63 ( bs , 1h ) , 7.09 ( dd , j = 8.6 hz , j = 1.9 hz , 1h ) , 7.137.26 ( m , 4h ) , 7.38 ( d , j = 8.6 hz , 1h ) , 7.66 ( d , j = 1.8 hz , 1h ) , 11.15 ( s , 1h ) ; c nmr ( 50 mhz , apt , dmso - d6 )  27.7 ( t ) , 28.0 ( q , 3c ) , ( ch2-group at 37.7 ppm in cdcl3 overlaps with dmso signal ) , 50.1 ( d ) , 79.3 ( s ) , 113.1 ( d ) , 117.0 ( s ) , 118.3 ( d ) , 121.2 ( d ) , 123.4 ( s ) , 125.6 ( d ) , 126.7 ( d ) , 126.8 ( d ) , 127.0 ( s ) , 127.9 ( d ) , 129.0 ( d ) , 134.4 ( s ) , 134.8 ( s ) , 135.6 ( s ) , 163.4 ( s ) ; c nmr ( 50 mhz , apt , cdcl3 )  28.3 ( t ) , 28.6 ( 3c , q ) , 37.7 ( t ) , 51.0 ( d ) , 79.3 ( s ) , 112.0 ( d ) , 118.9 ( s ) , 119.7 ( d ) , 122.6 ( d ) , 125.5 ( s ) , 125.7 ( d ) , 126.1 ( d ) , 126.8 ( d ) , 127.5 ( s ) , 128.3 ( d ) , 129.1 ( d ) , 134.7 ( s ) , 135.0 ( s ) , 135.8 ( s ) , 154.2 ( s ) yield for cu 245 mg ( 75% ) and for fe 184 mg ( 56% ) ; white powder ; mp 8385 c ; tlc rf ( pe : etoac=3:1 ) = 0.63 ; gc / ms ( ei+ ) m / z ( rel intensity ) 284 ( 14 ) , 283 ( 33 ) , 282 ( 40 ) , 281 ( 100 ) , 279 ( 22 ) , 265 ( 22 ) , 253 ( 35 ) , 252 ( 25 ) , 217 ( 30 ) , 216 ( 16 ) , 130 ( 27 ) , 103 ( 12 ) ; hrms ( esi ) : exact mass calculated for c22h23n2o2cl 405.1340 ; found 405.1339 [ m + na ] ; h nmr ( 200 mhz , cdcl3 )  1.52 ( s , 9h ) , 2.632.81 ( m , 1h ) , 2.903.20 ( m , 2h ) , 4.07 ( bs , 1h ) , 6.526.75 ( m , 2h ) , 7.05 ( dd , j = 8.6 hz , j = 1.8 hz , 1h ) , 7.107.23 ( m , 4h ) , 7.31 ( d , j = 1.7 hz , 1h ) , 7.68 ( bs , 1h ) , 8.19 ( bs , 1h ) ; h nmr ( 200 mhz , dmso - d6 )  1.45 ( s , 9h ) , 2.663.12 ( m , 3h ) , 3.90 ( bs , 1h ) , 6.50 ( s , 1h ) , 6.68 ( bs , 1h ) , 7.00 ( dd , j = 8.5 hz , j = 1.9 hz , 1h ) , 7.067.27 ( m , 4h ) , 7.41 ( d , j = 1.8 hz , 1h ) , 7.54 ( d , j = 7.5 hz , 1h ) , 11.09 ( s , 1h ) ; c nmr ( 50 mhz , apt , dmso - d6 )  27.8 ( t ) , 28.0 ( 3c , q ) , ch2 group at 37.5 ppm in cdcl3 overlaps with dmso signal , 50.2 ( d ) , 79.1 ( s ) , 111.2 ( d ) , 117.3 ( s ) , 119.0 ( d ) , 120.3 ( d ) , 124.8 ( s ) , 125.7 ( d ) , 126.0 ( s ) , 126.2 ( d ) , 126.6 ( d ) , 127.9 ( d ) , 128.9 ( d ) , 134.4 ( s ) , 135.8 ( s ) , 136.7 ( s ) , 153.4 ( s ) ; c nmr ( 50 mhz , apt , cdcl3 )  28.4 ( t ) , 28.5 ( 3c , q ) , 37.5 ( t ) , 50.5 ( d ) , 79.8 ( s ) , 110.9 ( d ) , 119.2 ( s ) , 120.5 ( d ) , 121.2 ( d ) , 125.1 ( s ) , 125.4 ( d ) , 125.7 ( d ) , 126.7 ( d ) , 128.2 ( s ) , 128.3 ( d ) , 129.1 ( d ) , 134.9 ( s ) , 135.9 ( s ) , 136.8 ( s ) , 154.4 ( s ) . yield for cu 155 mg ( 46% ) and for fe 235 mg ( 70% ) ; bright yellow powder ; mp 8891 c ; tlc rf ( pe / etoac 5/1 ) = 0.45 ; gc / ms ( ei+ ) m / z ( rel intensity ) 293 ( 56 ) , 292 ( 100 ) , 291 ( 17 ) , 290 ( 38 ) , 264 ( 15 ) , 263 ( 24 ) , 246 ( 20 ) , 244 ( 16 ) , 217 ( 32 ) , 216 ( 20 ) , 189 ( 13 ) , 188 ( 10 ) , 132 ( 21 ) , 130 ( 27 ) , 121 ( 16 ) , 108 ( 26 ) , 103 ( 13 ) ; h nmr ( 200 mhz , dmso - d6 )  1.46 ( s , 9h ) , 2.663.13 ( m , 3h ) , 3.92 ( d , j = 12.1 hz , 1h ) , 6.60 ( s , 1h ) , 6.73 ( bs , 1h ) , 7.067.29 ( m , 5h ) , 8.018.13 ( m , 2h ) , 11.80 ( s , 1h ) ; c nmr ( 50 mhz , apt , dmso - d6 )  27.7 ( t ) , 28.0 ( q , 3c ) , 37.0 ( t ) , 49.8 ( d ) , 79.3 ( s ) , 118.7 ( d ) , 118.9 ( d ) , 119.2 ( s ) , 125.8 ( d ) , 126.9 ( d ) , 127.6 ( d ) , 127.9 ( d ) , 128.2 ( d ) , 128.5 ( s ) , 129.1 ( d ) , 130.3 ( s ) , 132.6 ( s ) , 134.5 ( s ) , 135.2 ( s ) , 153.5 ( s ) . yield for cu 133 mg ( 44% ) and for fe 126 mg ( 42% ) ; white powder ; mp 8486 c ; tlc rf ( pe / et2o 1/1 ) = 0.11 ; gc / ms ( ei+ ) m / z ( rel intensity ) 249 ( 56 ) , 248 ( 100 ) , 245 ( 36 ) , 244 ( 57 ) , 219 ( 50 ) , 190 ( 10 ) , 144 ( 14 ) , 132 ( 24 ) , 130 ( 28 ) , 119 ( 34 ) , 109 ( 27 ) , 103 ( 18 ) , 95 ( 16 ) ; hrms ( esi ) exact mass calculated for c21h23n3o2 350.1863 ; found 350.1871 [ m + h ] ; h nmr ( 200 mhz , dmso - d6 )  1.45 ( s , 9h ) , 2.683.15 ( m , 3h ) , 3.92 ( d , j = 11.2 hz , 1h ) , 6.50 ( s , 1h ) , 6.77 ( bs , 1h ) , 7.03 ( dd , j = 7.9 hz , j = 4.7 hz , 1h ) , 7.097.28 ( m , 4h ) , 7.82 ( bs , 1h ) , 8.20 ( dd , j = 4.6 hz , j = 1.4 hz , 1h ) , 11.54 ( s , 1h ) ; c nmr ( 50 mhz , apt , dmso - d6 )  27.8 ( t ) , 28.0 ( q , 3c ) , 37.1 ( t ) , 50.4 ( d ) , 79.1 ( s ) , 115.3 ( d ) , 115.9 ( s ) , 118.2 ( s ) , 125.1 ( d ) , 125.7 ( d ) , 126.7 ( d ) , 127.1 ( d ) , 127.9 ( d ) , 128.9 ( d ) , 134.5 ( s ) , 135.4 ( s ) , 142.7 ( d ) , 148.4 ( s ) , 153.4 ( s ) . yield for cu 145 mg ( 44% ) and for fe no conversion ; white powder ; mp 8791 c ; tlc rf ( pe / et2o 1/5 ) = 0.28 ; gc / ms ( ei+ ) m / z ( rel intensity ) 286 ( 14 ) , 285 ( 35 ) , 284 ( 41 ) , 283 ( 100 ) , 254 ( 26 ) , 219 ( 11 ) , 191 ( 11 ) , 166 ( 6 ) , 130 ( 14 ) , 103 ( 8) ; hrms ( esi ) exact mass calculated for c20h21n4o2cl 385.1426 ; found 385.1423 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  1.42 ( s , 9h ) , 2.75 ( d , j = 16.2 hz , 1h ) , 2.943.38 ( m , 2h ) , 4.10 ( bs , 1h ) , 6.81 ( bs , 1h ) , 6.86 ( bs , 1h ) , 7.127.28 ( m , 4h ) , 8.64 ( s , 1h ) , 11.02 ( s , 1h ) ; c nmr ( 50 mhz , apt , cdcl3 )  28.0 ( t ) , 28.4 ( 3c , q ) , 38.2 ( t ) , 50.6 ( d ) , 80.2 ( s ) , 115.6 ( s ) , 119.0 ( s ) , 126.0 ( d ) , 127.0 ( d ) , 128.1 ( d ) , 129.3 ( d ) , 134.6 ( s ) , 135.8 ( s ) , 150.3 ( d ) , 152.4(s ) , 152.6 ( s ) , 155.0 ( s ) . 3h ( 150 mg , 0.450 mmol ) or 3i ( 50 mg , 0.138 mmol ) was suspended in ethylene glycol ( 3h , 20 ml ; 3i , 10 ml ) and microwaved at 250 c for 30 s ( hold time ) . the combined organic layers were washed twice with brine , dried over sodium sulfate , filtered , and evaporated . the crude product was purified by flash column chromatography ( 100 g of sio2 , pe / etoac 100/0  0/100 ( 30 min ) , etoac / etoh 95/5  60/40 ( 30 min ) ) . in the case of 3i the reaction mixture was diluted with water , chilled with liquid nitrogen , and lyophilized to afford the desired product as a pale brown solid . tmscl ( 272 mg , 2.50 mmol , 5.0 equiv ) was added dropwise to an argon - degassed solution of the corresponding boc - protected amine ( 0.5 mmol , 1.0 equiv ) in dry meoh ( 4 ml ) at room temperature , and the reaction mixture was stirred for 4 to 24 h under argon . after the reaction mixture was cooled to 0 c , it was poured into ice cold 2 n aqueous naoh . the suspension was extracted three times with etoac , and the combined organic layers were washed once with 2 n naoh . the combined organic layers were then dried over sodium sulfate , filtered , and evaporated to afford the desired product in quantitative yields . thiq ( 200 mg , 1.50 mmol , 1.0 equiv ) , catalyst ( 18.1 mg , 75 mol , 0.05 equiv ) , and the corresponding indole ( 1.80 mmol , 1.2 equiv ) were placed into a 5 ml glass vial in air and stirred for 10 min at 0 c . tbhp ( 390 l , 5.5 m in decane , 1.3 equiv ) was added dropwise at 0 c in air and the dark greenish slurry was stirred for 1 h at 0 c . the neat mixture was then slowly heated to 50 c ( within 1 h ) , whereupon the color changed to black and stirring was continued for 15 h in a heating block . the mixture was diluted with dcm ( 3 ml ) and directly subjected to flash column chromatography , using pe / etoac as eluent to afford the desired product . method a 95 mg ( 89% ) , method b 124 mg ( 100% ) , method c 179 mg ( 48% ) ; brown solid ; mp 4446 c ; tlc rf ( etoac / etoh 5/1 ) = 0.20 ; gc / ms ( ei+ ) m / z ( rel intensity ) 248 ( m , 38 ) , 247 ( 100 ) , 231 ( 15 ) , 219 ( 22 ) , 218 ( 32 ) , 217 ( 19 ) , 130 ( 20 ) ; hrms ( esi ) exact mass calculated for c17h16n2 249.1398 , found 249.1386 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  2.02 ( bs , 1h ) , 2.803.37 ( m , 4h ) , 5.51 ( s , 1h ) , 6.88 ( d , j = 1.9 hz , 1h ) , 6.957.23 ( m , 6h ) , 7.33 ( d , j = 8.0 hz , 1h ) , 7.49 ( d , j = 7.8 hz , 1h ) , 8.34 ( bs , 1h ) ; c nmr ( 50 mhz , apt , cdcl3 )  29.4 ( t ) , 41.5 ( t ) , 53.6 ( d ) , 111.3 ( d ) , 118.6 ( s ) , 119.1 ( d ) , 119.3 ( d ) , 121.8 ( d ) , 124.1 ( d ) , 125.6 ( d ) , 126.1 ( d ) , 126.2 ( s ) , 127.8 ( d ) , 128.8 ( d ) , 134.9 ( s ) , 136.5 ( s ) , 138.1 ( s ) . method a 35 mg ( 97% ) , method b 131 mg ( 100% ) , method c 4 mg ( 1% ) ; pale yellow solid ; mp 5558 c ; tlc rf ( etoac / etoh / tea 10/1/1 ) = 0.57 ; gc / ms ( ei+ ) m / z ( rel intensity ) 262 ( m , 60 ) , 261 ( 100 ) , 245 ( 6 ) , 233 ( 14 ) , 232 ( 24 ) , 217 ( 12 ) , 131 ( 22 ) , 130 ( 29 ) , 115 ( 11 ) , 108 ( 14 ) ; h nmr ( 200 mhz , cdcl3 )  2.52 ( s , 1h ) , 2.833.17 ( m , 3h ) , 3.193.35 ( m , 1h ) , 3.73 ( s , 3h ) , 5.52 ( s , 1h ) , 6.79 ( s , 1h ) , 6.977.36 ( m , 7h ) , 7.51 ( d , j = 7.9 hz , 1h ) ; c nmr ( 50 mhz , apt , cdcl3 )  29.7 ( t ) , 32.7 ( q ) , 41.5 ( t ) , 53.6 ( d ) , 109.3 ( d ) , 118.1 ( s ) , 119.1 ( d ) , 119.4 ( d ) , 121.7 ( d ) , 125.6 ( d ) , 126.1 ( d ) , 126.9 ( s ) , 127.9 ( d ) , 128.5 ( d ) , 128.9 ( d ) , 135.2 ( s ) , 137.2 ( s ) , 138.3 ( s ) . method b 131 mg ( 100% ) , method c 170 mg ( 43% ) ; pale yellow solid ; mp 6870 c ; tlc rf ( etoac / etoh 10/1 ) = 0.14 ; gc / ms ( ei+ ) m / z ( rel intensity ) 262 ( m , 86 ) , 261 ( 100 ) , 247 ( 24 ) , 245 ( 60 ) , 244 ( 37 ) , 233 ( 22 ) , 230 ( 21 ) , 218 ( 38 ) , 217 ( 41 ) , 130 ( 46 ) ; hrms ( esi ) exact mass calculated for c18h18n2 263.1543 , found 263.1548 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  1.94 ( bs , 1h ) , 2.35 ( s , 3h ) , 2.793.00 ( m , 1h ) , 3.033.46 ( m , 3h ) , 5.43 ( s , 1h ) , 6.797.28 ( m , 8h ) , 7.99 ( bs , 1h ) ; c nmr ( 50 mhz , apt , cdcl3 )  11.9 ( q ) , 29.8 ( t ) , 43.3 ( t ) , 53.6 ( d ) , 110.2 ( d ) , 113.6 ( s ) , 118.8 ( d ) , 119.2 ( d ) , 120.8 ( d ) , 125.9 ( d ) , 126.0 ( d ) , 127.3 ( s ) , 127.4 ( d ) , 128.8 ( d ) , 133.3 ( s ) , 134.9 ( s ) , 135.4 ( s ) , 138.5 ( s ) . method b 137 mg ( 99% ) , method c 202 mg ( 48% ) ; light brown solid ; mp 7476 c ; tlc rf ( etoac / etoh 5/1 ) = 0.11 ; gc / ms ( ei+ ) m / z ( rel intensity ) 278 ( m , 62 ) , 277 ( 100 ) , 261 ( 49 ) , 249 ( 26 ) , 248 ( 26 ) , 234 ( 10 ) , 233 ( 8) , 217 ( 7 ) , 132 ( 9 ) , 130 ( 12 ) ; hrms ( esi+ ) exact mass calculated for c18h18n2o 279.1492 ; found 279.1499 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  1.98 ( bs , 1h ) , 2.793.36 ( m , 4h ) , 3.76 ( s , 3h ) , 5.47 ( s , 1h ) , 6.796.88 ( m , 2h ) , 6.91 ( d , j = 2.3 hz , 1h ) , 6.957.18 ( m , 4h ) , 7.22 ( d , j = 8.7 hz , 1h ) , 8.18 ( bs , 1h ) ; c nmr ( 50 mhz , apt , cdcl3 )  27.8 ( t ) , 40.5 ( t ) , 52.9 ( d ) , 55.6 ( q ) , 100.8 ( d ) , 112.1 ( d ) , 112.2 ( d ) , 115.0 ( s ) , 126.1 ( d ) , 126.2 ( d ) , 126.6 ( s ) , 126.8 ( d ) , 128.1 ( d ) , 128.7 ( d ) , 131.5 ( s ) , 133.6 ( s ) , 135.8 ( s ) , 153.8 ( s ) . method b 146 mg ( 100% ) , method c 233 mg ( 53% ) ; shining dark yellow solid ; mp 8385 c ; tlc rf ( etoac / etoh 5/1 ) = 0.21 ; gc / ms ( ei+ ) m / z ( rel intensity ) 293 ( m , 43 ) , 292 ( 100 ) , 276 ( 12 ) , 263 ( 22 ) , 246 ( 31 ) , 218 ( 14 ) , 217 ( 27 ) , 130 ( 12 ) ; hrms ( esi ) exact mass calculated for c17h15n3o2 294.1237 ; found 294.1239 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  1.93 ( bs , 1h ) , 2.803.34 ( m , 4h ) , 5.51 ( s , 1h ) , 6.92 ( d , j = 7.6 hz , 1h ) , 6.977.23 ( m , 4h ) , 7.32 ( d , j = 9.0 hz , 1h ) , 8.06 ( dd , j = 9.0 hz , j = 2.1 hz , 1h ) , 8.51 ( d , j = 2.0 hz , 1h ) , 8.91 ( bs , 1h ) ; c nmr ( 50 mhz , cdcl3 )  29.4 ( t ) , 41.6 ( t ) , 53.5 ( d ) , 111.2 ( d ) , 117.1 ( d ) , 117.7 ( d ) , 121.9 ( s ) , 125.8 ( d ) , 125.9 ( s ) , 126.6 ( d ) , 127.0 ( d ) , 127.5 ( d ) , 129.3 ( d ) , 135.1 ( s ) , 137.2 ( s ) , 139.6 ( s ) , 141.5 ( s ) . method c 321 mg ( 58% ) ; pale yellow solid ; mp 195197 c ; tlc rf ( etoac / etoh 5/1 ) = 0.17 ; gc / ms ( ei+ ) m / z ( rel intensity ) 306 ( m , 41 ) , 305 ( 100 ) , 289 ( 8) , 276 ( 16 ) , 253 ( 20 ) , 244 ( 8) , 217 ( 14 ) , 191 ( 16 ) , 144 ( 8) , 130 ( 12 ) ; hrms ( esi ) exact mass calculated for c19h18n2o2 307.1441 , found 307.1446 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  1.77 ( bs , 1h ) , 2.793.33 ( m , 4h ) , 3.90 ( s , 3h ) , 5.55 ( s , 1h ) , 6.987.20 ( m , 5h ) , 7.36 ( d , j = 8.6 hz , 1h ) , 7.90 ( dd , j = 8.6 hz , j = 1.5 hz , 1h ) , 8.37 ( bs , 2h ) ; h nmr ( 200 mhz , dmso - d6 )  2.573.21 ( m , 5h ) , 3.78 ( s , 3h ) , 5.31 ( s , 1h ) , 6.79 ( d , j = 7.6 hz , 1h ) , 6.97 ( dt , j = 7.3 hz , j = 1.9 hz , 1h ) , 7.037.17 ( m , 2h ) , 7.19 ( d , j = 1.9 hz , 1h ) , 7.42 ( d , j = 8.6 hz , 1h ) , 7.69 ( dd , j = 8.6 , j = 1.4 hz , 1h ) , 8.19 ( d , j = 1.1 hz , 1h ) , 11.30 ( s , 1h ) ; c nmr ( 50 mhz , apt , cdcl3 )  25.8 ( t ) , 40.0 ( t ) , 51.8 ( q ) , 51.9 ( d ) , 111.5 ( d ) , 113.0 ( s ) , 121.6 ( d ) , 121.6 ( s ) , 123.2 ( d ) , 125.8 ( s ) , 126.8 ( d ) , 127.8 ( d ) , 128.0 ( d ) , 128.1 ( d ) , 128.7 ( d ) , 132.1 ( s ) , 132.9 ( s ) , 138.9 ( s ) , 168.1 ( s ) . method b 141 mg ( 100% , reaction time 7 h ) ; pale yellow solid ; mp 148151 c ; tlc rf ( etoac / et3n 11/1 ) = 0.29 ; gc / ms ( ei+ ) m / z ( rel intensity ) 284 ( 19 ) , 283 ( 38 ) , 282 ( m , 57 ) , 281 ( 100 ) , 254 ( 12 ) , 253 ( 19 ) , 252 ( 27 ) , 217 ( 30 ) , 131 ( 14 ) , 130 ( 26 ) , 109 ( 17 ) ; hrms ( esi ) : exact mass calculated for c17h15n2cl 283.0997 , found 283.0998 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  1.93 ( bs , 1h ) , 2.793.34 ( m , 4h ) , 5.43 ( s , 1h ) , 6.91 ( s , 1h ) , 6.94 ( d , j = 8.0 hz , 1h ) , 6.997.19 ( m , 4h ) , 7.23 ( d , j = 8.7 hz , 1h ) , 7.46 ( d , j = 1.8 hz , 1h ) , 8.36 ( s , 1h ) ; c nmr ( 50 mhz , apt , cdcl3 )  29.4 ( t ) , 41.7 ( t ) , 53.6 ( d ) , 112.3 ( d ) , 118.7 ( s ) , 118.8 ( d ) , 122.3 ( d ) , 125.1 ( s ) , 125.4 ( d ) , 125.7 ( d ) , 126.4 ( d ) , 127.3 ( s ) , 127.6 ( d ) , 129.0 ( d ) , 134.9 ( s ) , 134.9 ( s ) , 137.7 ( s ) . method b 122 mg ( 86% , reaction time 4 h ) , method c 197 mg ( 46% ) ; off white powder ; mp 146148 c ; tlc rf ( etoac / etoh 5/1 ) = 0.15 ; gc / ms ( ei+ ) m / z ( rel intensity ) 284 ( 18 ) , 283 ( 38 ) , 282 ( m , 56 ) , 281 ( 100 ) , 265 ( 10 ) , 253 ( 22 ) , 252 ( 28 ) , 217 ( 29 ) , 132 ( 19 ) , 131 ( 19 ) , 130 ( 35 ) , 123 ( 13 ) , 109 ( 29 ) ; hrms ( esi ) exact mass calculated for c17h15n2cl 283.0997 , found 283.1000 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  2.23 ( s , 1h ) , 2.793.37 ( m , 4h ) , 5.44 ( s , 1h ) , 6.87 ( s , 1h ) , 6.93 ( d , j = 7.6 hz , 1h ) , 6.967.09 ( m , 2h ) , 7.137.21 ( m , 2h ) , 7.25 ( d , j = 1.7 hz , 1h ) , 7.32 ( d , j = 8.5 hz , 1h ) , 8.61 ( s , 1h ) ; c nmr ( 50 mhz , apt , dmso - d6 )  20.3 ( t ) , 32.8 ( t ) , 45.1 ( d ) , 102.6 ( d ) , 109.7 ( s ) , 110.8 ( d ) , 111.7 ( d ) , 116.6 ( s ) , 117.1 ( d ) , 117.2 ( d ) , 117.9 ( d ) , 118.8 ( s ) , 119.4 ( d ) , 120.3 ( d ) , 126.4 ( s ) , 129.1 ( s ) , 129.5 ( s ) . method b 145 mg ( 99% , reaction time 6 h ) , method c : 7 mg ( 2% ) ; shining dark yellow solid ; mp 5861 c ; tlc rf ( etoac / meoh 11/1 ) = 0.35 ; gc / ms ( ei+ ) m / z ( rel intensity ) 293 ( m , 57 ) , 292 ( 100 ) , 264 ( 15 ) , 263 ( 23 ) , 246 ( 18 ) , 217 ( 26 ) , 189 ( 10 ) , 132 ( 10 ) , 131 ( 8) , 130 ( 14 ) , 109 ( 11 ) ; h nmr ( 200 mhz , cdcl3 )  1.87 ( bs , 1h ) , 2.793.36 ( m , 4h ) , 5.48 ( s , 1h ) , 6.90 ( d , j = 7.5 hz , 1h ) , 6.967.22 ( m , 5h ) , 7.84 ( d , j = 7.7 hz , 1h ) , 8.13 ( d , j = 8.1 hz , 1h ) , 9.86 ( bs , 1h ) ; c nmr ( 50 mhz , apt , cdcl3 )  29.6 ( t ) , 42.0 ( t ) , 53.8 ( d ) , 119.0 ( d ) , 119.3 ( d ) , 121.1 ( s ) , 125.7 ( d ) , 126.1 ( d ) , 126.5 ( d ) , 127.5 ( d ) , 128.4 ( d ) , 129.1 ( d ) , 130.0 ( s ) , 130.2 ( s ) , 132.9 ( s ) , 135.1 ( s ) , 137.6 ( s ) . method b 124 mg ( 100% ) , method c 160 mg ( 43% ) ; light brown solid ; mp 172174 c ; tlc rf ( etoac / etoh 5/1 ) = 0.11 ; gc / ms ( ei+ ) m / z ( rel intensity ) 249 ( m , 36 ) , 248 ( 100 ) , 232 ( 7 ) , 220 ( 18 ) , 219 ( 30 ) , 218 ( 11 ) , 131 ( 8) , 130 ( 10 ) , 119 ( 12 ) ; hrms ( esi ) exact mass calculated for c16h15n3 250.1339 ; found 250.1352 [ m + h ] ; h nmr ( 200 mhz dmso - d6 )  2.633.24 ( m , 4h ) , 3.70 ( s , 1h ) , 5.30 ( s , 1h ) , 6.80 ( d , j = 7.6 hz , 1h ) , 6.857.02 ( m , 2h ) , 7.037.18 ( m , 2h ) , 7.27 ( d , j = 1.3 hz , 1h ) , 7.66 ( dd , j = 7.8 hz , j = 1.3 hz , 1h ) , 8.15 ( d , j = 3.6 hz , 1h ) , 11.48 ( s , 1h ) ; c nmr ( 50 mhz , apt , dmso - d6 )  29.0 ( t ) , 41.7 ( t ) , 53.9 ( d ) , 114.8 ( d ) , 116.8 ( s ) , 118.4 ( s ) , 124.8 ( d ) , 125.2 ( d ) , 125.8 ( d ) , 127.0 ( d ) , 128.0 ( d ) , 128.7 ( d ) , 135.0 ( s ) , 138.5 ( s ) , 142.3 ( d ) , 148.9 ( s ) . method c 189 mg ( 48% ) ; pale brown solid ; mp 141144 c ; tlc rf ( etoac / etoh 5/1 ) = 0.12 ; gc / ms ( ei+ ) m / z ( rel intensity ) 262 ( m , 56 ) , 261 ( 100 ) , 245 ( 11 ) , 233 ( 14 ) , 232 ( 21 ) , 217 ( 12 ) , 132 ( 9 ) , 131 ( 12 ) , 130 ( 20 ) , 115 ( 10 ) ; h nmr ( 200 mhz , cdcl3 )  2.08 ( bs , 1h ) , 2.48 ( s , 3h ) , 2.813.37 ( m , 4h ) , 5.51 ( s , 1h ) , 6.87 ( d , j = 2.3 hz , 1h ) , 6.947.22 ( m , 6h ) , 7.307.41 ( m , 1h ) , 8.26 ( bs , 1h ) ; c nmr ( 50 mhz , apt , cdcl3 )  16.6 ( q ) , 29.6 ( t ) , 41.7 ( t ) , 53.9 ( d ) , 117.0 ( d ) , 119.8 ( d ) , 120.5 ( s ) , 122.6 ( d ) , 123.7 ( d ) , 125.6 ( d ) , 125.9 ( s ) , 126.1 ( d ) , 127.9 ( d ) , 128.9 ( d ) , 135.0 ( s ) , 136.1 ( s ) , 138.2 ( s ) . thiq ( 999 mg , 7.50 mmol , 2.0 equiv ) , catalyst ( 45.3 mg , 0.188 mmol , 0.05 equiv ) , and the corresponding pyrrole ( 3.75 mmol , 1.0 equiv ) were placed in a 5 ml glass vial in air and cooled to 0 c and stirred for 10 min . tbhp ( 975 l , 5.5 m in decane , 1.3 equiv ) was added dropwise at 0 c in air and the dark greenish slurry stirred for 1 h at 0 c . the neat mixture was then slowly heated to 50 c ( within 1 h ) , upon which the mixture turned black , and stirred for 15 h in a heating block . the mixture was diluted with dcm ( 3 ml ) and directly subjected to flash chromatography , using etoac / etoh as eluent . due to polar unidentified impurities , the desired product was further purified by preparative hplc . 327 mg ( 44% ) ; white solid ; mp 117118 c ; tlc rf ( etoac / etoh 5/1 ) = 0.11 ; gc / ms ( ei+ ) m / z ( rel intensity ) 198 ( m , 50 ) , 197 ( 100 ) , 182 ( 99 ) , 169 ( 36 ) , 168 ( 95 ) , 167 ( 40 ) , 132 ( 46 ) , 131 ( 28 ) , 130 ( 60 ) , 115 ( 21 ) , 103 ( 21 ) , 77 ( 22 ) ; hrms ( esi ) exact mass calculated for c13h14n2 199.1230 , found 199.1223 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  2.07 ( s , 1h ) , 2.76 ( dt , j = 16.4 hz , j = 5.3 hz , 1h ) , 2.843.26 ( m , 3h ) , 5.14 ( s , 1h ) , 6.06 ( dd , j = 3.3 hz , j = 2.5 hz , 1h ) , 6.14 ( dd , j = 5.7 hz , j = 2.8 hz , 1h ) , 6.68 ( dd , j = 4.1 hz , j = 2.5 hz , 1h ) , 6.957.04 ( m , 1h ) , 7.057.23 ( m , 3h ) , 9.11 ( s , 1h ) ; c nmr ( 50 mhz , apt , cdcl3 )  29.2 ( t ) , 41.9 ( t ) , 55.1 ( d ) , 107.4 ( d ) , 107.9 ( d ) , 117.6 ( d ) , 125.6 ( d ) , 126.5 ( d ) , 127.6 ( d ) , 129.1 ( d ) , 133.7 ( s ) , 134.8 ( s ) , 137.0 ( s ) . 230 mg ( 27% ) ; off - white crystals ; mp 127129 c ; tlc rf ( etoac / etoh / tea 10/1/1 ) = 0.53 ; gc / ms ( ei+ ) m / z ( rel intensity ) 226 ( m , 100 ) , 225 ( 96 ) , 209 ( 79 ) , 208 ( 56 ) , 196 ( 38 ) , 194 ( 32 ) , 182 ( 39 ) , 167 ( 28 ) , 132 ( 24 ) , 130 ( 36 ) , 94 ( 78 ) , 91 ( 28 ) ; hrms ( esi ) exact mass calculated for c15h18n2 227.1543 ; found 227.1544 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  1.84 ( s , 1h ) , 2.13 ( s , 3h ) , 2.15 ( s , 3h ) , 2.713.15 ( m , 3h ) , 3.32 ( dt , j = 15.9 hz , j = 7.0 hz , 1h ) , 5.01 ( s , 1h ) , 5.51 ( d , j = 2.3 hz , 1h ) , 6.90 ( d , j = 6.9 hz , 1h ) , 6.987.13 ( m , 3h ) , 7.74 ( s , 1h ) ; c nmr ( 50 mhz , cdcl3 )  11.1 ( q ) , 12.9 ( q ) , 29.9 ( t ) , 42.6 ( t ) , 54.1 ( d ) , 105.9 ( d ) , 122.5 ( s ) , 123.2 ( s ) ,   125.1 ( s ) , 125.5 ( d ) , 125.6 ( d ) , 127.7 ( d ) , 128.7 ( d ) , 135.0 ( s ) , 139.8 ( s ) . 387 mg ( 41% ) ; pale yellow solid ; mp 115117 c ; tlc rf ( etoac / etoh 5/1 ) = 0.14 ; gc / ms ( ei+ ) m / z ( rel intensity ) 252 ( m , 46 ) , 251 ( 52 ) , 236 ( 56 ) , 223 ( 44 ) , 222 ( 39 ) , 194 ( 31 ) , 180 ( 39 ) , 132 ( 43 ) , 131 ( 65 ) , 130 ( 100 ) , 105 ( 32 ) , 103 ( 31 ) , 93 ( 72 ) , 77 ( 31 ) ; hrms ( esi ) exact mass calculated for c17h20n2 253.1699 , found 253.1692 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  1.681.88 ( m , 4h ) , 2.21 ( s , 1h ) , 2.442.55 ( m , 4h ) , 2.683.30 ( m , 4h ) , 5.10 ( s , 1h ) , 5.76 ( d , j = 2.3 hz , 1h ) , 7.037.21 ( m , 4h ) , 8.27 ( s , 1h ) ; c nmr ( 50 mhz , apt , cdcl3 )  22.7 ( t ) , 22.8 ( t ) , 23.4 ( t ) , 23.8 ( t ) , 29.3 ( t ) , 41.6 ( t ) , 55.1 ( d ) , 107.1 ( d ) , 116.1 ( s ) , 125.5 ( d ) , 126.4 ( d ) , 126.8 ( s ) , 127.8 ( d ) , 129.0 ( d ) , 131.8 ( s ) , 134.9 ( s ) , 137.1 ( s ) . 55 mg ( 11% ) ; yellow oil ; tlc rf ( pe / etoac 5/1 ) = 0.53 ; gc / ms ( ei+ ) m / z ( rel intensity ) 298 ( m , 8) , 242 ( 49 ) , 198 ( 30 ) , 197 ( 100 ) , 182 ( 42 ) , 168 ( 26 ) , 167 ( 15 ) , 132 ( 10 ) , 130 ( 18 ) , 57 ( 20 ) ; h nmr ( 200 mhz , cdcl3 )  1.51 ( s , 9h ) , 2.703.03 ( m , 2h ) , 3.26 ( bs , 1h ) , 3.98 ( bs , 1h ) , 5.58 ( bs , 1h ) , 6.02 ( dd , j = 5.0 hz , j = 2.5 hz , 1h ) , 6.30 ( bs , 1h ) , 6.73 ( dd , j = 4.1 hz , j = 2.5 hz , 1h ) , 7.147.23 ( m , 4h ) , 9.14 ( s , 1h ) ; c nmr ( 101 mhz , cdcl3 )  28.6 ( q , 3c ) , 28.7 ( t ) , 39.1 ( t ) , 51.6 ( d ) , 80.2 ( s ) , 107.1 ( d ) , 107.7 ( d ) , 117.7 ( d ) , 125.9 ( d ) , 127.0 ( d ) , 128.5 ( d ) , 128.6 ( d ) , 134.1 ( s ) , 134.3 ( s ) , 135.2 ( s ) , 156.2 ( s ) . 2-protected 1,2,3,4-tetrahydroisoquinoline ( pg = boc , 200 mg ; pg = bz , 203 mg ; pg = cbz ; 229 mg ; 0.857 mmol , 1.0 equiv ) , catalyst ( cu(no3)23h2o , 10.4 mg ; fe(no3)39h2o , 17.3 mg ; 42.9 mol , 0.05 equiv ) , and the methoxybenzene derivative ( 1.03 mmol , 1.2 equiv ) were placed into a 5 ml glass vial . tbhp ( 203 l , 5.5 m in decane , 1.3 equiv ) was added dropwise at 0 c in air and the reaction mixture stirred for 10 min at 0 c . the neat mixture was then slowly heated to 50 c and stirred for 15 h in a heating block . the reaction mixture was diluted with dcm ( 3 ml ) and directly subjected to flash column chromatography . the desired product was obtained after mplc , where the solvent mixture used for tlc was also used for column chromatography ( 100 g of sio2 ) . if necessary , the product was finally purified by preparative hplc . yield for cu 260 mg ( 76% ) and for fe 278 mg ( 81% ) ; white solid ; mp 109111 c ; tlc rf ( pe / et2o 1/1 ) = 0.10 ; gc / ms ( ei+ ) m / z ( rel intensity ) 348 ( 24 ) , 299 ( 60 ) , 298 ( 100 ) , 282 ( 26 ) , 268 ( 90 ) , 239 ( 14 ) , 180 ( 18 ) , 179 ( 20 ) , 151 ( 16 ) , 132 ( 9 ) ; hrms ( esi ) : exact mass calculated for c23h29no5 400.2118 , found 400.2122 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  1.28 ( s , 9h ) , 2.733.01 ( m , 2h ) , 3.49 ( ddd , j = 12.6 hz , j = 10.6 hz , j = 4.5 hz , 1h ) , 3.69 ( s , 6h ) , 3.81 ( s , 3h ) , 4.304.45 ( m , 1h ) , 6.12 ( s , 2h ) , 6.45 ( s , 1h ) , 6.80 ( d , j = 7.2 hz , 1h ) , 6.957.16 ( m , 3h ) ; c nmr ( 50 mhz , apt , cdcl3 )  28.3 ( 3c , q ) , 30.5 ( t ) , 39.4 ( t ) , 49.4 ( d ) , 55.2 ( q ) , 55.5 ( 2c , q ) , 79.1 ( s ) , 90.5 ( 2c , d ) , 114.0 ( s ) , 125.4 ( d ) , 125.8 ( d ) , 126.3 ( d ) , 127.9 ( d ) , 135.2 ( s ) , 137.2 ( s ) , 155.4 ( s ) , 158.8 ( 2c , s ) , 160.1 ( s ) . yield for cu 159 mg ( 46% ) and for fe 187 mg ( 54% ) ; white solid ; mp 6769 c ; tlc rf ( pe / et2o 1/1 ) = 0.09 ; gc / ms ( ei+ ) m / z ( rel intensity ) 403 ( m , 7 ) , 373 ( 26 ) , 372 ( 100 ) , 299 ( 4 ) , 298 ( 13 ) , 282 ( 6 ) , 105 ( 10 ) , 77 ( 9 ) ; hrms ( esi ) exact mass calculated for c25h25no4 404.1856 , found 404.1852 [ m + h ] ; h nmr ( 400 mhz , dmso - d6 , 80 c )  2.86 ( bs , 1h ) , 3.61 ( s , 6h ) , 3.633.74 ( m , 1h ) , 3.78 ( s , 3h ) , 4.07 ( bs , 1h ) , 6.21 ( s , 2h ) , 6.64 ( bs , 1h ) , 6.72 ( d , j = 7.5 hz , 1h ) , 7.04 ( t , j = 7.4 hz , 1h ) , 7.10 ( t , j = 7.2 hz , 1h ) , 7.137.26 ( m , 3h ) , 7.317.44 ( m , 3h ) ; c nmr ( 101 mhz , dmso - d6 , 80 c )  29.5 ( t ) , 49.2 ( s ) , 54.8 ( q ) , 55.4 ( q , 2c ) , 91.4 ( d , 2c ) , 112.4 ( s ) , 125.1 ( d ) , 125.4 ( d , 2c ) , 126.0 ( d , 2c ) , 127.4 ( d ) , 127.5 ( d , 2c overlapping ) , 128.3 ( d ) , 134.3 ( s ) , 136.5 ( s ) , 137.3 ( s ) , 158.4 ( s ) , 159.9 ( s , 2c ) , 169.2 ( s ) . yield for cu 190 mg ( 51% ) and for fe 215 mg ( 58% ) ; pale yellow solid ; mp 115116 c ; tlc rf ( pe / et2o 1/1 ) = 0.32 ; gc / ms ( ei+ ) m / z ( rel intensity ) 433 ( m , 1 ) , 342 ( 3 ) , 299 ( 20 ) , 298 ( 100 ) , 283 ( 5 ) , 282 ( 17 ) , 90 ( 6 ) ; hrms ( esi ) exact mass calculated for c26h27no5 434.1962 , found 434.1966 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  2.753.06 ( m , 2h ) , 3.293.79 ( m , 7h ) , 3.83 ( s , 3h ) , 4.46 ( d , j = 11.0 hz , 1h ) , 5.03 ( d , j = 16.7 hz , 1h ) , 5.09 ( d , j = 17.4 hz , 1h ) , 6.08 ( s , 2h ) , 6.56 ( s , 1h ) , 6.79 ( d , j = 7.3 hz , 1h ) , 6.967.41 ( m , 8h ) ; c nmr ( 50 mhz , apt , cdcl3 )  30.4 ( t ) , 39.9 ( t ) , 49.3 ( d ) , 55.2 ( q ) , 55.4 ( q , 2c ) , 66.8 ( t ) , 90.8 ( d , 2c ) , 113.3 ( s ) , 125.5 ( d ) , 125.9 ( d ) , 126.2 ( d ) , 127.5 ( d ) , 127.8 ( d ) , 127.9 ( d , 2c ) , 128.2 ( d , 2c ) , 134.7 ( s ) , 136.0 ( s ) , 137.0 ( s ) , 155.6 ( s ) , 158.9 ( s ) , 160.2 ( s , 2c ) . yield for cu 80 mg ( 23% ) and for fe 160 mg ( 47% ) ; white solid ; mp 8486 c ; tlc rf ( pe / et2o 3/1 ) = 0.13 ; hrms ( esi ) exact mass calculated for c23h29no5 400.2118 , found 400.2123 [ m + h ] ; gc / ms ( ei+ ) m / z ( rel intensity ) 399 ( m , 4 ) , 343 ( 5 ) , 299 ( 58 ) , 298 ( 100 ) , 284 ( 24 ) , 268 ( 73 ) , 253 ( 12 ) , 239 ( 12 ) , 168 ( 8) , 132 ( 15 ) ; h nmr ( 200 mhz , cdcl3 )  1.40 ( s , 9h ) , 2.753.07 ( m , 2h ) , 3.353.55 ( m , 1h ) , 3.69 ( s , 3h ) , 3.77 ( s , 3h ) , 3.87 ( s , 3h ) , 4.034.24 ( m , 1h ) , 6.53 ( s , 1h ) , 6.42 ( s , 1h ) , 6.56 ( s , 1h ) , 7.017.17 ( m , 4h ) ; c nmr ( 50 mhz , apt , cdcl3 )  28.3 ( 3c , q ) , 29.0 ( t ) , 39.1 ( t ) , 53.0 ( q ) , 56.0 ( q ) , 56.1 ( d ) , 56.7 ( q ) , 79.4 ( s ) , 97.5 ( d ) , 113.8 ( d ) , 124.2 ( s ) , 125.9 ( d ) , 126.2 ( d ) , 127.8 ( d ) , 128.4 ( d ) , 134.8 ( s ) , 136.7 ( s ) , 142.4 ( s ) , 148.8 ( s ) , 151.5 . yield for cu 170 mg ( 46% ) and for fe 190 mg ( 52% ) ; pale yellow solid ; mp 116118 c ; tlc rf ( pe / et2o 2/1 ) = 0.17 ; gc / ms ( ei+ ) m / z ( rel intensity ) 429 ( m , 8) , 329 ( 27 ) , 328 ( 100 ) , 299 ( 10 ) , 298 ( 49 ) , 183 ( 10 ) , 132 ( 20 ) , 130 ( 10 ) , 57 ( 12 ) ; hrms ( esi ) : exact mass calculated for c24h31no6 430.2224 , found 430.2230 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  1.33 ( s , 9h ) , 2.743.03 ( m , 2h ) , 3.403.61 ( m , 4h ) , 3.75 ( s , 3h ) , 3.75 ( s , 3h ) , 3.88 ( s , 3h ) , 4.36 ( d , j = 12.3 hz , 1h ) , 6.29 ( s , 1h ) , 6.48 ( s , 1h ) , 6.80 ( d , j = 6.9 hz , 1h ) , 6.967.16 ( m , 3h ) ; c nmr ( 50 mhz , apt , cdcl3 )  28.3 ( q , 3c ) , 30.2 ( t ) , 39.4 ( t ) , 49.8 ( d ) , 55.7 ( q ) , 55.9 ( q ) , 59.8 ( q ) , 60.7 ( q ) , 79.2 ( s ) , 91.7 ( d ) , 118.9 ( s ) , 125.6 ( d ) , 125.7 ( d ) , 126.5 ( d ) , 128.1 ( d ) , 135.1 ( s ) , 136.5 ( s ) , 137.3 ( s ) , 152.6 ( s ) , 152.7 ( s ) , 153.6 ( s ) , 155.1 ( s ) . yield for cu 131 mg ( 41% ) and for fe 108 mg ( 34% ) ; white solid ; mp 3637 c ; tlc rf ( pe / et2o 1/1 ) = 0.33 ; hrms ( esi ) exact mass calculated for c22h27no4 370.2013 , found 370.2010 [ m + h ] ; gc / ms ( ei+ ) m / z ( rel intensity ) 269 ( 46 ) , 268 ( 100 ) , 252 ( 22 ) , 239 ( 12 ) , 238 ( 32 ) , 132 ( 15 ) , 130 ( 10 ) ; h nmr ( 200 mhz , cdcl3 )  1.42 ( s , 9h ) , 2.81 ( dt , j = 16.0 hz , j = 3.9 hz , 1h ) , 2.99 ( ddd , j = 15.9 hz , j = 10.3 hz , j = 5.6 hz , 1h ) , 3.293.48 ( m , 1h ) , 3.78 ( s , 3h ) , 3.82 ( s , 3h ) , 3.994.22 ( m , 1h ) , 6.34 ( dd , j = 8.4 hz , j = 2.4 hz , 1h ) , 6.47 ( s , 1h ) , 6.48 ( s , 1h ) , 6.83 ( d , j = 8.3 hz , 1h ) , 7.007.18 ( m , 4h ) ; c nmr ( 101 mhz , cdcl3 )  28.3 ( q , 3c ) , 28.8 ( t ) , 38.6 ( t ) , 52.6 ( d ) , 55.15 ( q ) , 55.19 ( q ) , 79.3 ( s ) , 98.4 ( d ) , 103.4 ( d ) , 125.1 ( s ) , 125.9 ( d ) , 126.2 ( d ) , 127.9 ( d ) , 128.5 ( d ) , 130.0 ( d ) , 135.0 ( s ) , 136.8 ( s ) , 154.7 ( s ) , 158.0 ( s ) , 159.9 ( s ) . isochroman 9 ( 200 mg , 1.49 mmol , 1.0 equiv ) , catalyst ( cu(no3)23h2o , 18.0 mg ; fe(no3)39h2o , 30.1 mg ; 74.5 mol , 0.05 equiv ) , and the corresponding methoxybenzene ( 1.79 mmol , 1.2 equiv ) were placed into a 5 ml glass vial . tbhp ( 352 l , 5.5 m in decane , 1.3 equiv ) was added dropwise at 0 c in air and the reaction mixture stirred for 10 min at 0 c . the neat mixture was then slowly heated to 50 c and stirred for 15 h in a heating block . finally , the reaction temperature was raised to 80 c , and the reaction mixture was stirred for another 24 h. the reaction was monitored by tlc and/or gc - ms . the reaction mixture was diluted with dcm ( 3 ml ) and directly subjected to flash column chromatography . the desired product was obtained after mplc , where the solvent mixture used for tlc was also used for column chromatography ( 100 g of sio2 ) . if necessary , the product was finally purified by preparative hplc . yield for cu 230 mg ( 51% ) and for fe 246 mg ( 55% ) ; white solid ; mp 118120 c ; tlc rf ( pe / et2o 1/1 ) = 0.32 ; gc / ms ( ei+ ) m / z ( rel intensity ) 300 ( m , 50 ) , 282 ( 22 ) , 272 ( 50 ) , 269 ( 100 ) , 251 ( 26 ) , 241 ( 98 ) , 239 ( 48 ) , 208 ( 23 ) , 195 ( 27 ) , 181 ( 35 ) , 168 ( 22 ) , 139 ( 28 ) ; hrms ( esi ) exact mass calculated for c18h20o4 301.1434 ; found 301.1442 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  2.66 ( d , j = 15.9 hz , 1h ) , 3.093.35 ( m , 1h ) , 3.61 ( s , 6h ) , 3.80 ( s , 3h ) , 3.93 ( dt , j = 11.2 hz , j = 3.1 hz , 1h ) , 4.30 ( ddd , j = 11.1 hz , j = 5.6 hz , j = 1.9 hz , 1h ) , 6.12 ( s , 2h ) , 6.30 ( s , 1h ) , 6.67 ( d , j = 7.6 hz , 1h ) , 6.927.12 ( m , 3h ) ; c nmr ( 50 mhz , apt , cdcl3 )  29.0 ( t ) , 55.2 ( q ) , 55.9 ( 2c , q ) , 65.3 ( t ) , 70.2 ( d ) , 91.4 ( 2c , d ) , 111.7 ( s ) , 124.2 ( d ) , 125.1 ( d ) , 125.5 ( d ) , 127.8 ( d ) , 133.8 ( s ) , 139.7 ( s ) , 159.9 ( 2c , s ) , 161.2 ( s ) . yield for cu 190 mg ( 39% ) and for fe 85 mg ( 17% ) ; white solid ; mp 5558 c ; tlc rf ( pe / etoac 5/1 ) = 0.19 ; gc / ms ( ei+ ) m / z ( rel intensity ) 330 ( m , 100 ) , 315 ( 23 ) , 312 ( 14 ) , 299 ( 99 ) , 284 ( 10 ) , 271 ( 18 ) , 238 ( 16 ) , 198 ( 24 ) , 195 ( 16 ) , 183 ( 23 ) ; hrms ( esi ) exact mass calculated for c19h22o5 331.1540 , found 331.1544 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  2.69 ( d , j = 16.0 hz , 1h ) , 3.46 ( s , 3h ) , 3.143.35 ( m , 1h ) , 3.69 ( s , 3h ) , 3.78 ( s , 3h ) , 3.88 ( s , 3h ) , 3.914.02 ( m , 1h ) , 4.32 ( ddd , j = 11.1 hz , j = 5.6 hz , j = 1.7 hz , 1h ) , 6.25 ( s , 1h ) , 6.30 ( s , 1h ) , 6.69 ( d , j = 7.3 hz , 1h ) , 6.967.17 ( m , 3h ) ; c nmr ( 50 mhz , apt , cdcl3 )  28.9 ( t ) , 55.9 ( q ) , 56.3 ( q ) , 60.5 ( q ) , 60.8 ( q ) , 65.3 ( t ) , 70.8 ( d ) , 92.7 ( d ) , 116.8 ( s ) , 124.5 ( d ) , 125.4 ( d ) , 125.6 ( d ) , 128.1 ( d ) , 133.8 ( s ) , 136.7 ( s ) , 139.6 ( s ) , 153.5 ( s ) , 153.8 ( s ) , 154.5 ( s ) . yield for cu 92 mg ( 23% ) and for fe 48 mg ( 12% ) ; colorless oil ; tlc rf ( pe / et2o 1/1 ) = 0.28 ; gc / ms ( ei+ ) m / z ( rel intensity ) 270 ( m , 65 ) , 255 ( 100 ) , 239 ( 43 ) , 225 ( 16 ) , 209 ( 16 ) , 194 ( 13 ) , 178 ( 8) , 165 ( 24 ) , 104 ( 10 ) , 77 ( 8) ; hrms ( esi ) exact mass calculated for c17h18o3 271.1329 ; found 271.1324 [ m + h ] ; h nmr ( 200 mhz , cdcl3 )  2.84 ( dt , j = 16.3 hz , j = 4.4 hz , 1h ) , 3.013.22 ( m , 1h ) , 3.81 ( s , 3h ) , 3.88 ( s , 3h ) , 3.904.03 ( m , 1h ) , 4.18 ( dt , j = 11.0 hz , j = 5.0 hz , 1h ) , 6.22 ( s , 1h ) , 6.43 ( dd , j = 8.4 hz , j = 2.4 hz , 1h ) , 6.55 ( d , j = 2.4 hz , 1h ) , 6.80 ( d , j = 7.4 hz , 1h ) , 6.96 ( d , j = 8.4 hz , 1h ) , 7.037.21 ( m , 3h ) ; c nmr ( 50 mhz , apt , cdcl3 )  28.8 ( t ) , 55.3 ( q ) , 55.6 ( q ) , 63.3 ( t ) , 72.2 ( d ) , 98.4 ( d ) , 104.2 ( d ) , 123.3 ( s ) , 125.8 ( d ) , 126.2 ( d ) , 126.6 ( d ) , 128.5 ( d ) , 130.7 ( d ) , 134.2 ( s ) , 137.9 ( s ) , 158.6 ( s ) , 160.5 ( s ) yield for cu 145 mg ( 32% ) and for fe 67 mg ( 15% ) ; white solid ; mp 4648 c ; tlc rf ( pe / etoac 5/1 ) = 0.39 ; gc / ms ( ei+ ) m / z ( rel intensity ) 300 ( m , 100 ) , 285 ( 35 ) , 269 ( 39 ) , 257 ( 9 ) , 239 ( 26 ) , 225 ( 9 ) , 208 ( 12 ) , 195 ( 14 ) , 168 ( 25 ) , 153 ( 13 ) ; hrms ( esi ) exact mass calculated for c18h20o4 301.1434 , found 301.1436 [ m + h ] ; h nmr ( 400 mhz , cdcl3 )  2.80 ( dt , j = 16.2 hz , j = 3.2 hz , 1h ) , 3.21 ( ddd , j = 16.0 hz , j = 10.0 hz , j = 5.8 hz , 1h ) , 3.73 ( s , 3h ) , 3.89 ( s , 3h ) , 3.93 ( s , 3h ) , 3.99 ( dt , j = 11.1 hz , j = 3.8 hz , 1h ) , 4.27 ( ddd , j = 11.2 hz , j = 5.6 hz , j = 3.1 hz , 1h ) , 6.20 ( s , 1h ) , 6.61 ( s , 1h ) , 6.66 ( s , 1h ) , 6.78 ( d , j = 7.6 hz , 1h ) , 7.057.12 ( m , 1h ) , 7.147.21 ( m , 2h ) ; c nmr ( 101 mhz , apt , cdcl3 )  28.8 ( t ) , 56.0 ( q ) , 56.4 ( q ) , 56.8 ( q ) , 64.4 ( t ) , 72.6 ( d ) , 97.4 ( d ) , 113.0 ( d ) , 122.2 ( s ) , 125.8 ( d ) , 126.2 ( d ) , 126.5 ( d ) , 128.5 ( d ) , 133.9 ( s ) , 138.0 ( s ) , 143.2 ( s ) , 149.4 ( s ) , 151.9 ( s ) .