An Old Dog with New Tricks: Enjoin Wolff-Kishner Reduction for Alcohol Deoxygenation and C-C Bond Formations

The Wolff-Kishner reduction, discovered in the early 1910s, is a fundamental and effective tool to convert carbonyls into methylenes via deoxygenation under strongly basic conditions. For over a century, numerous valuable chemical products have been synthesized by this classical method. The reaction proceeds via the reversible formation of hydrazone followed by deprotonation with the strong base to give an N-anionic intermediate, which affords the deoxygenation product upon denitrogenation and protonation. By examining the mechanistic pathway of this century old classical carbonyl deoxygenation, we envisioned and subsequently developed two unprecedented new types of chemical transformations: a) alcohol deoxygenation and b) C-C bond formations with various electrophiles including Grignard-type reaction, conjugate addition, olefination, and diverse cross-coupling reactions.