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8.1.20.3 Method 3: Reaction with Aldehydes and Ketones

DOI: 10.1055/sos-SD-008-00403

Durst, T.; Khodaei, M.Science of Synthesis, (20068667.

The reaction of α-lithio sulfoxides of the type 33 with aldehydes or unsymmetrical ketones gives products bearing a new chiral center at the β-carbon (1,3-induction). Typically, the creation of this chiral center is not very selective;[‌14‌‌16‌] however, transmetalation of 33 with zinc(II) bromide[‌17‌] improves the diastereomeric ratio for reaction with benzaldehyde from near 1:1 to 4:1.[‌34‌,‌35‌] One of relatively few exceptions is the reaction of the lithio sulfoxide 33 (Ar1=1-naphthyl) with aromatic aldehydes and alkyl aryl ketones (Scheme 12).[‌36‌] The high asymmetric induction in these cases is attributed to a chair-like transition state with π-stacking between the naphthyl and aryl rings. Raney nickel desulfurization leads to the formation of optically active alcohols 34 in high overall yield and with high enantiomeric purity. For the α-lithio derivatives of alkyl tert-butyl sulfoxides, essentially complete control of the α-center and moderate control of the β-center has been reported,[‌6‌,‌37‌] especially when the aldehyde is somewhat hindered. The anti-1,2- and anti-2,3- stereochemistry is preferred. The introduction of a potential complexing group, either as a spectator substituent such as in an alkyl imidazole sulfoxide,[‌38‌] or a remote hydroxy (alkoxy) group on the alkyl chain, leads to high 1,2-asymmetric induction in the reaction of these species with aldehydes,[‌29‌‌31‌] i.e. the conversion of 35 into 36 with greater than 9:1 diastereoselectivity (Scheme 12).[‌30‌,‌31‌] The analogue of 35, devoid of the remote hydroxy group, shows, almost no selectivity.

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References