Stereochemistry of hydride reductions

Percentage alcohol favored by steric approach control 

Reducing agent % axial % axial % axial %endo YoCXO 

The highest stereoselectivity reported to date apparently is that of lithium tris(5-butyl)borohydride. This reagent is sufficiently bulky that even 4-alkyl-cyclohexanones are reduced by equatorial approach, giving the axial alcohol. 

The stereochemistry of reduction of acyclic ketones can be predicted on the basis of steric factors. An asymmetric carbon atom adjacent to the carbonyl center undergoing reduction can control the direction of approach of the reducing agent  

Steric factors arising from groups more remote from the center undergoing reduction can also influence the stereochemical course of reduction. These steric 

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Attempts have been made to account for the stereochemistry of hydride reductions of asymmetric cyclohexanones. Until recently the most widely accepted view was that of Dauben, Noyce and their co-workers, who... 

Stereochemistry of hydride reduction Hydride converts a planar sp -hybridized carbonyl carbon to a tetrahedral p -hybridized carbon. Thus, hydride reduction of an achiral ketone with LiAlH4 or NaBH4 gives a racemic mixture of alcohol when a new stereocentre is formed. 

The stereochemistry of hydride reduction and Grignard addition was discussed previously in Sections 20.5 and 20.1 OB, respectively. 

With less hindered hydride donors, particularly sodium borohydride and lithium aluminum hydride, cyclohexanones give predominantly the equatorial alcohol. There has been less agreement about the factors that lead to this result. The equatorial alcohols are, of course, the more stable of the two isomers. The stereochemistry of hydride reduction is determined by kinetic control, but it was argued that the relative stability of the equatorial alcohol might be reflected in the transition state and be the dominant factor when no major steric problems intervened. The term product development control was introduced to indicate this explanation of the reaction stereochemistry. A number of objections were raised to this idea, primarily on the basis of the Hammond principle. The common hydride reductions are exothermic reactions with low activation energies. The transition state should resemble starting ketone and reflect little of the structural features that are present in the product, so that it is difficult to see why product stability should determine the product composition. 

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