Twisted amide reduction under Wolff-Kishner conditions: Synthesis of a benzo-1-aza-adamantane derivative

A synthesis of 4,5-benzo-1-aza-tricyclo[4.3.1.1(3,8)]undecane (1), a benzo-1-aza-adamantane derivative, is described and features a previously unknown application of the Wolff-Kishner reduction of a nonresonance stabilized or twisted amide. An intermediate amino ester is converted to a severely twisted amide, which, when exposed to hydrazine in alcohol, provides the corresponding twisted amino hydrazone. Wolff-Kishner conditions (KOH/ethylene glycol, 200 degreesC) provide the reduced target 1 without hydrolysis to amino acid derivatives. These operations are conveniently performed in a single flask in high yield.