Comparative reductive desymmetrization of 2,2-disubstituted-cycloalkane-1,3-diones

Reductive desymmetrization of 2-methyl-2-substituted-cycloalkane-1,3-diones can be effected using either NaBH₄ in DME or lithium tri-tert-butoxyaluminum hydride (LTBA) in THF at −60 °C. The former is a new approach that offers slightly greater diastereoselectivity in the reduction of 2,2-disubstituted-cyclopentane-1,3-diones while LTBA is superior with 2,2-disubstituted-cyclohexane-1,3-diones. Both conditions minimize subsequent reduction to diols thereby furnishing high yields of 1,3-ketols. Particularly rapid monoreductions are observed with 2-methyl-2-nitroethylcyclopentane-1,3-dione and 2-cyanoethyl-2-methylcyclopentane-1,3-dione when treated with NaBH₄ in DME at −60 °C. As expected, diastereoselectivity varies considerably with the substitution at C-2.