Reduction with chiral reducing agents

Reduction of one carbonyl group of the prochiral dione (53) with chiral reducing agents has produced mixtures of a- (the OH groups at either C-14 or C-17 a-oriented as the molecule is usually depicted) and /3 -alcohols with disappointingly low discrimination.18... 

The enantioselective reduction of y-nitroketones and y-nitrodiketones by the chiral reducing agent (+)- or (-)-dusopinocamphenylchloroborane (DIP-C1 ) gives nitro alcohols having from 33 to 86% ee and nitrodiols with complete diastereoselectivity and > 95% ee.122... 

In summary, a number of effective chiral reducing agents have been developed based on the modification of LAH. Excellent results have been obtained with aryl alkyl ketones and a,p-acetylenic ketones. However, dialkyl ketones are reduced in much lower enantiomeric excess. This clearly indicates that steric effects alone do not control stereoselectivity in these reductions. Systematic studies have been carried out with the objective of designing improved reagents. A better understanding of the mechanisms and knowledge of the active species is required in order to provide more accurate models of the transition states of the key reduction steps. 

CBS reagent (Section 20.6A) A chiral reducing agent formed by reacting an oxazaborolidine with BH3. CBS reagents predictably give one enantiomer as the major product of ketone reduction. 

Lithium borohydride decomposed by /V-benzoylcysteine (61) or /V/v -dibenzoylcystine (62), a sulfur-containing modifier, is a highly efficient chiral reducing agent. A complex prepared from (61), t-butyl alcohol and LiBH4 affords carbinols in maximum 92% ee by the reduction of aryl alkyl ketones in THF at -78 °C (Scheme 13). A LiBH4 complex with (62) and t-butyl alcohol is useful for the reduction of -keto esters to give (R)-P-hydroxy esters in up to 91 % ee. In both cases the use of r-butyl alcohol is essential in order to achieve efficient enantiofacial differentiation. ... 

Cho, B. T., Chun, Y. S. Asymmetric reduction of a-functionalized ketones with organoboron-based chiral reducing agents. ACS Symp. Ser. 2001,783, 122-135. 

Aldrich, ( )-DlP-Chloride]31. These latter two reagents are complementary with respect to enantiomeric excesses obtainable from various ketones (- j-DIP-Chloride is especially effective in the reduction of hindered acetylenic ketones37. Various chiral reducing agents have been compared38 and in recent reviews 30,39 the stereochemistry of Meerwein-Ponndorf-Verley reductions has been discussed in connection with other reduction methods. 

Conceptually, there are several distinct ways in which the asymmetric reduction of an a-keto ester to the corresponding optically active a-hydroxy ester can be achieved (a) reduction of a chiral ester with an achiral reducing agent (b) reduction of an achiral ester with a chiral reducing agent and (c) a combination of a chiral ester and a chiral reducing agent ( double asymmetric reduction ). 

Some years ago, these possibilities were examined [53] with (—)-menthyl benzoylformate and ethyl benzoylformate. A simple asymmetric reduction involving either (—)-menthyl benzoylformate with an acliiral agent, liAlH4(LAH)-cyclo-hexanol, process (a), or ethyl benzoylformate with a chiral reducing agent, LAH-(+)-camphor, process (b), gave (/ )-mandelic acid after hydrolysis, in relatively low optical yields (10 and 4% e.e., respectively). On the other hand, the double asymmetric reduction , process (c), resulted in 49% asymmetric synthesis. This result is more than would be anticipated on the basis of a simple additive effect. 

Asymmetric Reduction of a-Functionalized Ketones with Organoboron-Based Chiral Reducing Agents... 

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