Stereo- and Chemodivergent NHC-Promoted Functionalisation of Arylalkylketenes with Chloral**

Stereo- and chemodivergent enantioselective reaction pathways are observed upon treatment of alkylarylketenes and trichloroacetaldehyde (chloral) with N-heterocyclic carbenes, giving selectively either β-lactones (up to 88:12 dr, up to 94 % ee) or α-chloroesters (up to 94 % ee). Either 2-arylsubstitution or an α-branched iPr alkyl substituent within the ketene favours the chlorination pathway, allowing chloral to be used as an electrophilic chlorinating reagent in asymmetric catalysis.

[c] Determined by chiral HPLC analysis.
[c] Determined byc hiral HPLC analysis. The observed change in reactivity from formal [2+ +2] cycloaddition to chlorination with variation in the ketene structure was also investigated computationally using 1,4-dimethyltria-zol-5-ylidene as am odel NHC catalyst with methyl-2-methylphenylketene and isopropylphenylketene ( Figure 2). Grimme's B3LYP-D3(BJ) functional [21] and the 6-31G(d,p )b asis set [22] were used for geometry optimisation and ZPE calculation, with final energies calculated using the TZVPP basis set. [23] Using these constraints, transition structures for both the formal [2+ +2] cycloaddition and a-chlorination reactions from methyl-2-methylphenylketene and iso-propylphenylketenew ere located (Figure 2). In accordance with the resultso fZ hang et al. [24] the transition states forr eactions of the (E)-enolates were significantly lower in energy than those of the (Z)-enolates (see SI for all calculated transition state structures and energies). Using both of these ketenes, transition states for a-chlorination over the formal [2+ +2] cycloaddition process leading to the b-lactones weref avoureds ignificantly as observed experimentally. For b-lactone formation,t he transition state leadingt ot he synproduct was favoured overt he anti-. [25] In the calculated transition states, the forming CÀCb onds in the formal [2+ +2] cycloaddition are significantly shorter (22,1 .88 ; 23,1 .87 ) than the developing CÀCl bonds (24,2 .24 ; 25,2 .37 ). This is consistent with the electrophilic chlorine in the S N 2-type chlorination transition state being less sterically demanding than the sp 2 -hybridised carbonyl carbon in the formal [2+ +2] cycloaddition reaction. With either a2 -substituent within the aromatic substituent of the alkylarylketene, or ab ranched iso-propyl group, the additional sterice ncumbrance of these substituents disfavours the formal [2+ +2] addition, resulting in the chlorination processb eing preferred.
Building upon this model, the observedc hemodivergent reaction pathwaysa re proposed to arise from initial NHC addition to the ketene, with preferentialo nwards reaction arising from the (E)-azolium enolate 26.S ubsequents tereoselective formal [2+ +2] cycloaddition with chloral generates 28,w ith eliminationo ft he NHC giving the b-lactonea nd completing the catalytic cycle. Alternatively, the use of chloral as an electrophilic chlorinating agent results in the formation of an acyl azolium and enolate ion pair 27 that combined to give the observed a-chloroester.N otably,a ssuming these mechanistic extremes,stereodivergent reaction pathways are observed from the (E)-azolium enolatei ntermediate 26. Reface functionalisation of the enolate derived from sterically nondemanding ketenes (such as 1) leads to the observed b-lactone configuration. Conversely, Si-face functionalisation with ketenes bearing either a2 -substituted aryl unit or an a-branched isopropyls ubstituent providest he configuration observed for the chlorinated esters (Figure 3).

Scheme4.[a]
Yieldo fisolated product. [b] Determined by chiralH PLC analysis. Computational studies on am odel system have allowed the structural parameters that lead to selectivity in these reaction processes to be analysed. Current research from this laboratory is directed toward developing alternative uses of NHCs and other Lewis bases in asymmetric catalysis.

Experimental Section
For general experimental details, full characterisation data, NMR spectra and HPLC traces, see the Supporting Information.
General procedure (1): Lactonisation and chlorination at 0 8 8C To af lame dried Schlenk flask under an argon atmosphere was added NHC precatalyst (0.10 mmol), base (0.09 mmol) and toluene (6 mL) and the mixture stirred for 15 min. The mixture was then cooled to 0 8Ci na nice/H 2 Ob ath followed by addition of a08Cs olution of the requisite ketene (1.00 mmol) in toluene (12 mL), immediately followed by chloral (1.00 mmol). To luene (2 mL) was added to wash residual reactants into solution and the reaction was stirred for the stated time at 0 8Cb efore opening the flask to the air for 30 min and concentration in vacuo. The resulting crude residue was purified by flash silica chromatography (ether:petrol) to provide either the isolated lactone or chlorinated ester as stated.
General procedure (2): Lactonisation and chlorination at 0 8 8C with dropwise ketene addition In instances where ketene dimerization was competitive with lactonisation or chlorination the ketene was added dropwise. To aflame dried Schlenk flask under an argon atmosphere was added NHC precatalyst (0.10 mmol), base (0.09 mmol) and toluene (6 mL) and the mixture stirred for 15 min. The mixture was then cooled to 0 8C in an ice/H 2 Ob ath followed by addition of chloral (1.00 mmol). A 0 8Cs olution of the requisite ketene (1.00 mmol) in toluene (12 mL) was subsequently added over 0.5 h. The reaction was stirred for an additional 3h at 0 8Cb efore opening the flask to the air for 0.5 h and concentration in vacuo. The resulting crude residue with the stated diastereomeric ratio was purified by flash silica chromatography (ether:petrol) to provide either the isolated lactone or chlorinated ester.