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Please login or sign up for a free trial to access the full content. 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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Mee eeeeeeee eeeeeeee eeee eee eeeeeeee ee α-eeeeee-α-eeeeee eeeeeeeeee eeee eee eeeeeeeeeeeee eeee eeee 8,8-eeeeeeeeeeeeeeeeee eee, eeeee eeeeeeeeee, eeee 8,8-eeeeeeeee. Meeeeeeeeeeeeeeeee eeeeee eeeeeeeee (88), eeeeeeeee eeeeeeee eeee eeeeeeeeeee eeeeeee 88 ee eeeeee eeee eee ee eee eee eeeeeeee eeeeeeeeeeeee 88, eeeee eeee eeeeeeeee eeee eeeeeeeeee eeeeeeeee eeeeeeeee, eeeee eee eeeeeeeeeeeeeeeeee eeee eeeeeeee-eeeeeeeeeee eeeeeeee 88 (Meeeee 88).[‌88‌]

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Mee eeeeeeeeeeeeeee eeee α-eeeeeeeeeeeeeee 88 eeeee ee eee eeeeeeeeeeeee eeee eeeeeeeeeeee eeee 8-eeeeeeeeeeeeee. Me eeee 88, eee eeeeeeeeeeeeeee ee eee α-eeeeee ee eeeeeeeeee ee eee eeeeeeeeeeeeeee ee eee eeeeeeeee, eeeee M eeeeeeeeeeeee ee eee eeeeee eeee eeeeeeee M eeeeeeeeeeeee ee eee α-eeeeee; eeeeeee, eee eeeeee eeeeeeeeeee eeee eeeeeee ee eeeeeeee ee eee eeeeeeee eeeeeeee eeeee ee eeee 8:8.[‌88‌] Mee eeeeeeeee eeeee eeeeeeeeeeee eee ee eeeeeeee ee eee eeeeeee 88. Meeeeeeeee eeeeeeee eeee eeeeeeeeeeee eeeeee ()-eeeeeeeeee [()-88] ee e eeeee ee 88% eee eee eeee eeee (Meeeee 88). Mee eeeeee eeeeeeee eeeeeeee e eeeeee eeeeeeee ee eee eeeeeeeee (eee Meeeeee Meee eeeeeeeee eee eeeee eeee eeeeeeeee eeeee eee eeeeeeeeeee eeee eeeeeeeee eeee eeeeeeeeeeeee eeee ee eeeeeee eeeeeeeeeee eeeeeeee, eeee ee α-eeeeeeee eeeeeeeeeee, eeeee. Mee eeeeeeeeee ee 88 eeee ()-eeeeeeeeee [()-88] eeeeeeeeee ee eeeeeeeeeee eeeeeeeeeee ee eee eeeeeeeee eeeeee eeeeeeee eeeeeeee.

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M eeeeee eeeee ee eeeeeeee eee ee eeeeeeee eeee eee eeeeeeeeeee eeeeeeee eeee eee eeeeeeee ee eeeeeeeeeeee eeeeee eeeeeeeee eeee eeeeeee eeeeeeeeeeeee, ee eeeeee eeeeeeeee ee eee eeee-eeeee eeeeeeeee ee eee eeeeeeeee eeeee. Mee eeeeeee, eeeeeee eee eeeeeeeee eeee eeee eeeeeeeee eeee eeeeeeeeeee α,β-eeeeeeeeeee eeeeeee ee e eeeee-eeee eeeeeeeee, eeeeeeeeeee ee eee eeeeeeeeee ee eeeeeeeeeeeeee eeee eeeeeeeee-8-eee-8-eeeeeeeeeeee (88) (Meeeee 88).[‌88‌] Mee eeeee eeee eee ee eeeeeeeeeeee ee eeeeeeeee eee eeeeeeeeeeee eeeeeeeeeeeeee eeeeeee 88 ee eeeeee, ee eeeeeee ee eeeeee eeeeeeee. Meeeeee eeeeee eee eeee 88% eee e eeeeee ee eeeeee eeeeeee. Mee eeeeeeeee eeeeeeee eeeeeee eee eeeeeee eeee eeeeeee ee eeeeeeee e α-eeeeeee eeeeeeeee eeeeeeeeeee. Meee ee e eeeeee eee eeeeeeeeeee ee eee eeeeee eeeeee eeeeeeeee eee eeeeeee.

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Meee eeeeeeee eee eeee eeee eeeeeeeeeee ee eee eeeeeeeee ee e eeeeee ee eeeeee eeeeeeeee. Mee eeeeeeeeeee ee 88, ee eeeeeeeeeeee ee eee eeeeeeeee ee (+)-eeeeeeeee[‌88‌] eee (+)-eeeeeeeeeee,[‌88‌] eee eeee eeeeeee eee ee eeeee-eeeeeee eeee eeeeee eeee 88 (Meeeee 88).[‌88‌] Me eeeeeee eeeee ee 88% ee eeeeeeee eee eee eeeee eeeee, eeeeeee eeeeeeeeeeee ee eee eeeeeeeeeeeee.

Meeeee 88 Me α-Meeeee Meeeeeeee Meee ee eee Meeeeeeee ee Meeeee Meeeeeeee[‌88‌]

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α-Meeeeeeeeee eeeeeeeeee eeeeeee eeeeeeee eeee eeeeeee eee eeeeeeeee ee eeee, eeeeeeeee, e eeeeeee ee α- eee γ-eeeeeeeeeeeeeeeee eeeeeeee.[‌88‌]

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(8M,88M)-88-Meeeee-8,8,88,88-eeeeeeeeee-8M-8,88-eeeeeeeeeeeeeeee[e]eeeeee-8-eeeeeeeeeeee (88):[‌88‌]

Me e eeeeeee eeee ee MMM (8.8eee) ee MMM (888eM) eee eeeeee (888eM) ee 88°M eeeee eeeee, eee eeeee eeeeeeeeeeee eeeeee eeeeeeeee (88e, 8.8eee). Mee eeeeeeeee eeeeee eeeeeee eee eeeeeee eee 88eee ee 88°M, eeeee eeeee eeee eeeeee ()-88 (88e, 8.88eee) eee eeeee eeeeeeee eee eeeeeee eeee e eeeeee ee 8e. Mee eeeeeee eee eeeeeee eee 8e, eee eeee eeeeeee ee eeee ee ee, eee eeeeeee eeee MMM (8M). M 8.8M ee eeee ee MMM (8.8M) eee eeeee, eee eee eeeeeeeeeeeee eeeeeee eee eeeeeee ee ee eee 88e. Mee eeeeeee eeeee eee eeeeeeeee eee eee eeeeeee eeeee eee eeeeeeeee eeee MeMMe (8×8M). Mee eeeeeeee eeeeeee eeeeee eeee eeeeee eeee eee. ee MM8Me (888eM) eee eee. eeeee (888eM), eee eeee eeeee (M8MM8). Mee eeeeeee eee eeeeeee eeeee eeeeeee eeeeeeee. Mee eeeeeee eee eeeeeeeee ee eee eeeeeee (8M) eeeeeeeeee MeMeM8 (88e), eee eee eeeeeeeee eeeeee eee eeeeeeee eee 8e. Mee eeeeee eeeeeee eee eeeeeee eeee MM8Me8 (8M). Mee eeeeeeeee eeeeeee eeeee eee eeeeee eeee eee. ee MM8MM (888eM) eee eeeee (888eM), eee eeee eeeee (M8MM8), eee eee eeeeeee eee eeeeeee. Meeeeeeeeeee ee eee eeeee eeeeeee ee eeeeee eeeeeeeeeeeeee eeee eee eeee eeeeeeee 88; eeeee: 88e (88%).