Reduction of a-heterosubstituted keton

Fig. 17.49. Reductions of a-heterosubstituted ketones to a-unsubstituted ketones (see Figures 15.34 and 17.59 for the preparation of compounds A and B, respectively). Here, a ketyl is formed as a radical anion intermediate (for more details about ketyls see Section 17.4.2). The ketyl obtained from A releases a chloride ion, the ketyl resulting from B releases a hydroxide ion. In each case, an enol radical is formed thereby which picks up an electron. This leads to the formation of a zinc enolate from which the final product is generated by protonation.

Tetradentate chiral proton donors have been used for the asymmetric protonation of samarium enolates formed by the Sml2 reduction of a-heteroatom-substituted carbonyl compounds. For example, Takeuchi examined the reduction of a-heterosubstituted cyclohexanone 12 using Sml2 and the BINOL-derived chiral proton source 13.41 Ketone 14 was obtained in good yield and high enantiomeric excess (Scheme 2.11). Coordination of the proton source to samarium is key to the success of the transformation.41... 

Samarium(n) iodide provides a route for the reduction of a-heterosubstituted carbonyl substrates. A wide range of a-hetero-substitutedketones is rapidly reduced to the corresponding unsubstituted ketone under mild conditions (eq A) The reaction is highly selective and may be performed in the presence of isolated iodides as well as isolated ketones. ... 

A variety of a-heterosubstituted ketones and similar substrates are reduced by Sml2 under mild conditions, to form unsubstituted ketones. The heteroatom functionalities that can be re-ductively cleaved include halides (-1, -Br, -Cl), -SR, -S(0)R, -SO2R, and -OR (Molander and Hahn, 1986b Smith et al., 1988). Reductive cleavage of some of these heteroatom substituents requires the presence of HMPA as cosolvent for greater efficiency (Kusuda et al., 1989). a,f-Qpoxy ketones are also reduced to 0-hydroxy carbonyl compounds as shown in eq. (13) (Otsubo et al., 1987a). This is an important pathway for the synthesis of chiral f-hydroxy carbonyl compounds as the chiral substrates are easily synthesized by the sharpless epoxidation reactions. -epoxy esters require more vigorous conditions and the presence of HMPA for efficient reduction. 

Similar yields of p-heterosubstituted alcohols have been observed 35) with deoxybenzoin and 2,2,6-trimethylcyclohexanone for all three heterosubstituted lithio derivatives if the reactions are performed at — 78 °C in THF (Scheme 34 g, i), whereas the best results are obtained when (methylseIeno)eyclopropyllithium is reacted at the same temperature but in ether instead of THF (Scheme 34 h, j)). This is probably due to a reduction of the degree of enolisation of the starting ketone when ether is used 87). This is a tendency which proved to be general for other a-selenoalkyl-lithiums 7 8-9-12)... 

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