Reduction of a-halo ketones

Borohydrides reduce a-substituted ketones to the corresponding a-substituted alcohols, and such products can be further reduced to olefins (see section VIII). Other reagents serve, through participation of the carbonyl group, to remove the substituent while leaving the ketone intact. The zinc or chromous ion reduction of a-halo ketones is an example of this second type, which is not normally useful for double bond introduction. However, when the derivative being reduced is an a,jS-epoxy ketone, the primary product is a -hydroxy ketone which readily dehydrates to the a,jS-unsaturated ketone. Since... 

Formation of oxiranes on the sterically more hindered side of the steroid ring system is usually carried out via /raw -halohydrins which afford oxiranes on treatment with base (c -Halohydrins yield ketones on exposure to base). Two general methods are available for the synthesis of tm s-halohydrins (1) the reduction of a-halo ketones and (2) the addition of a hypohalous acid to unsaturated steroids. 

Reduction of a-halo ketones. a-Bromo and a-chloro ketones are reduced to the purent ketone hy this reagent in CM iC N at room temperature in 3 12 hours. Yields tre in I he range 75 )5" . 

Asymmetric reduction of a-halo ketones. An a-halo substituent increases the rate and cnantioselectivity of reduction of aryl ketonc by neat 1. Chemical yields of chloro-and bromohydrins thus obtained arc usually >90 optical yields are usually also >90%. Chemical yields in reduction of a-iodo ketones. ire lower because of dciodination. The absolute configuration is (R) when 1 is derived fiom ( + )-a-pincnc. As expected, optical yields are lower when the reduction is conducted with aliphatic a-halo ketones. 

Reduction of a-halo ketones, This complex in combination with sodium iodide reduces a-halo ketones to the parent ketone in 80-90% yield. Sodium iodide and triethylamine-sulfur dioxide is more selective in that only aryl a-haloalkyl ketones are reduced. 

Dehalogenation (7, 247). The reduction of a-halo ketones to the corresponding ketone by Mo(CO) is facilitated by use of this metal carbonyl adsorbed on alumina. Yields are considerably higher because products of condensation are not formed, and the rate of reduction is markedly enhanced with the supported reagent. ... 

Fukuzawa et al. foimd that reduction of a-halo ketones followed by aldol reaction with aldehydes or ketones is prtMnoted by Ceb, CeCls/Nal or CeCb/SnCh. These reactions are carried out at room... 

Reduction of a-halo ketones. Dehalogenation is carried out in the presence of the... 

Reduction of a-halo ketones to the carbonyl compounds can be accomplished with DIBAL in the presence of Tln(II) Chloride and N,N,N, N -Tetramethylethylenediamine (eqs 4 and 5). Under these conditions, vicinal dibromides are converted to the corresponding alkenes. 

Asymmetric synthesis of 8-functionalized optically active secondary alcohols was realized hy TarB-N02-catalyzed enantios-elective reduction of a-halo ketones to an intermediate terminal epoxide and sequential ring opening with various nucleophiles. Optically active st)Tene oxide was prepared from a-bromoacetophenone with NaBH4 and TarB-N02 in high yield and with high enantioselectivity (98% 3ueld and 94% ee). fi-Functionalized secondary alcohols could be obtained from the epoxides by nucleophilic attack under appropriate conditions (eq41). 

Optically active halohydrins or styrene oxide derivatives obtained by the reduction of a-halo ketones followed by treatment with base have been widely used as key intermediates in the synthesis of many chiral drugs containing the p-amino alcohol moiety. Examples of such drugs include (R)-denopamine (13) [46a], (R)-isoproterenol (14) [46b], d-solatol (15) [47], (R)-fluoro(nor)epinephrine (16) [48], (R)-salmeterol (17) [49], and (R,R)-formoterol (18) [50] (Scheme 11.4). Most OABs were effective for the reduction of 2-bromo- or 2-chloroacetophenone derivatives (22), providing the corresponding halohydrins with high enantioselectivities (Table 11.4). 

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