Enantioselective synthesis of substituted 1-sulfonylcyclopropanols. In order to apply the procedure detailed above to the formation of chiral, substituted 1-sulfonylcyclopropanol derivatives, one would need to access the corresponding enantioenriched hemiketal intermediates prior to addition of the sulfinate salt. While the Simmons-Smith cyclopropanation of α-substituted silyl ketene acetals, leading to such hemiketals, has previously been reported, 14 it is not general, leads to mixtures of diastereomers, and to date, cannot be efficiently performed in an enantioselective manner (Figure , left). Alternatively, one could envision a reductive cyclization of NMR Yield (%) enantioenriched α-substituted β-chloroesters (Figure , right), although such a process is only known for a 2-methyl-substituted hemiketal (R 1 = H, R 2 = Me). Moreover, the radical character of this transformation strongly limits the nature of the possible substituents around the cyclopropane ring, in addition to the fact that access to such halogenated substrates in their enantioenriched form is not straightforward and generally requires multiple steps. For these reasons, we decided to design and optimize a more direct and practical approach involving a base-mediated α-hydroxylation of enantioenriched sulfonylcyclopropanes (Figure ), which are readily accessible substrates with a wide variety of possible substitution patterns (vide infra). 15 Unlike with carbonyl compounds and carboxylic acid derivatives, a significant challenge inherent to the α-hydroxylation of sulfones is the propensity of the resulting α-sulfonyl alkoxide intermediates to decompose to the corresponding carbonyl compound and sulfinic acid salt through α-elimination. In this case, such an event would lead to the cyclopropanone that would likely decompose under the reaction conditions. Because of the endothermic nature of this undesired elimination, it was envisioned that performing the reaction with a highly reactive electrophilic reagent at -78 °C could minimize this undesired pathway and allow us to isolate reasonable amounts of the chiral 1-sulfonylcyclopropanols (Table ). While the use of common electrophilic hydroxylation reagents such as oxaziridines led to either poor yield or undesired side-products (entries 1-3), it was found that the use of bis(triethylsilyl) peroxide D as oxidant, previously reported for the radical alkylation of amides, afforded promising results when added in the presence of BF3•OEt2 (entries 4-9). In order to obtain a substantial yield of the hydroxylated product, it was found that quenching the reaction at -78 °C using a solution of AcOH in toluene was necessary to protonate the α-sulfonyl alkoxide intermediate initially formed at low temperature, and thus suppress its decomposition following αelimination (entry 4 vs 5). Changing the solvent from THF to either t-BuOMe or DME significantly increased the yield (entries 12-13), both affording similar results for 5a but later found to give significantly different yields depending on the substrate, likely due to variations in solubility. 11 A number of enantioenriched arylsubstituted substrates (4a-4e) were readily prepared using Iwasa's Ru-catalyzed asymmetric cyclopropanation of alkenes with αdiazomethyl phenyl sulfone (Scheme 3, Method A). 15a Using our αhydroxylation conditions, highly enantioenriched 1sulfonylcyclopropanols 5a-5e were obtained in moderate to excellent yields as single diastereomers favoring retention of configuration at the α-position, as evidenced by X-ray crystallographic analysis (5a). a Determined by 1 H NMR analysis of the crude mixture using either 1,3,5-trimethoxybenzene or maleic acid as standard. The αbenzoylated product (57%) was obtained. c An α-dihydrocinnamoylated product (23%) was obtained resulting from equilibration to cyclopropanone. Reaction was quenched at -78 °C with a solution of AcOH in toluene prior to warming to rt. e Isolated yield. Reaction was quenched after 15 min instead of 2 h. Scheme 3. Scope of accessible substituted 1-sulfonylcyclopropanols via α-hydroxylation of cyclopropylsulfones a,b a Isolated yields. b Enantiomeric excesses determined by HPLC analysis using a chiral stationary phase (ee of 4 in parentheses). Racemic substrate 4 was used. The corresponding cyclopropanone is achiral.