Propargylic alcohol, Midland reduction

Midland and others reported that B-isopinocampheyl-9-borabicyclo[3.3.l]no-nane [Alpine-Borane (7 )-79] is an effective reagent for the highly asymmetric reduction of alkynyl ketones to afford the propargylic alcohol 8030 (Scheme 4.3z). The reagent (R)-19 is prepared from (+)-a-pinene and 9-borabicyclo[3.3.1]no-nane (9-BBN) and often represented as 19banana. The levels of asymmetric... 

Alkynic ketones have been used extensively in natural product synthesis, due in large part to the contributions of Midland and coworkers and the development of generd methods for enantioselective reduction of this moiety to afford optically active propargyl alcohols using chiral trialkylboranes. Furthermore, the derived alkynic alcohol is a versatile system which can be manipulated directly into cis-or rra 5-allylic alcohols and as a precursor for vinylorganometallic species. This section will briefly cover progress made in the direct acylation of alkynic organolithiums with the acylation protocol d veloped by Weinreb (see also Section 1.13.2.7). 

Extension of this methodology to an enantioselective variant soon followed. In 1979 Midland showed that by using the chiral reagent derived from hydroboration of a-pinene by 9-BBN (3), deuterium labeled benzaldehyde (6b) could be reduced to enantiomerically enriched alcohol 7b in 98% ee Subsequent studies found that 3 was also useful for the enantioselective reduction of acetylinic ketones (8) to propargylic alcohols (9).4... 

In a totally different approach, Noyori et al. have used binaphthol-modifled aluminum hydride reagent for enatioselective reduction of alkynyl ketones. Suitably modified boranes can be used for stereoselective reduction of ketones. Along these same lines. Midland" has developed Alpine borane (1, Scheme 21.5), which is excellent for several acetylenic ketones but has been found inefficient for hindered ot,p-acetylenic ketones. To overcome this problem, Brown et al." have introduced P-chlorodiisopinocamphenyl borane 2(-)-DIP-Cl (2, (Scheme 21.5), which reacts well with hindered ketones to provide the corresponding propargyl alcohols in 96 to 99% e.e. 

Midland and coworkers [13,14] achieved the reduction of sterically less congested propargyl ketones with AIpine-Borane. The reduction is accomplished using 2 equiv of 0.5-M solutions of AIpine-Borane (Table 26.11) [14]. Terminal acetylenic ketones and acetylenic ketoesters are completely reduced after 8 h at room temperature. Internal acetylenic ketones require 1-4 days at room temperature for complete reductions. The optically active chromanyl substrates (entries 7, 8) yield diastereomeric alcohols with (R,R) R,S) ratios of 85 15 for internal and 91 9 for the terminal acetylenes with the AIpine-Borane derived from (-i-)-a-pinene of 100% ee. The reagent obtained from pure (-)-a-pinene affords 18 82 ratio of the two diastereomeric internal propargylic alcohols. 

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