Ketones, cyclic 3,5-substituted, hydride reductions

The stereochemical product ratio for the reduction of cyclic ketones by hydrides is affected by the structure of the cyclic ketone and the nature of the hydride used. The reduction of substituted cyclohexanones avoids product interconversion by conformational ring flip because of conformationally locked cyclohexanones. In such cases, axial attack is preferred over equatorial attack. 4-fert-Butylcyclohexanone (6.50) is reduced by NaBH4 and by LiAlH4 to give 86% and 92% of trans-4-fert-butylcyclohexanol (6.51), respectively. Hindered hydrides such as f-BusBHLi show more selectivity. 

A large amount of data has been accumulated on the stereoselectivity of reduction of cyclic ketones.81 Table 5.4 compares the stereochemistry of reduction of several ketones by hydride donors of increasing seric bulk. The trends in the table illustrate the increasing importance of steric approach control as both the hydride reagent and the ketone become more highly substituted. The alkyl-substituted borohydrides have especially high selectivity for the least hindered direction of approach. 

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