Asymmetric synthesis. 29. Preparation of 1,8-diazaspiro[5.5]undecane derivatives

From 2-cyano-6-phenyloxazolopiperidine, two highly efficient routes have been developed for the asym. synthesis of the spiropiperidine system: 1,8-diazaspiro[5.5]undecane. The key step was generation of the imine salts from the functionalized alpha -amino nitrile I, by nucleophilic addn. of a suitable organometallic reagent to the nitrile group followed by, in situ, intramol. nucleophilic alkylation. A reductive-cyclization procedure allowed the prepn. of nonsubstituted and monosubstituted spiro compds. II (R = H, pentyl), while an alkylation-cyclization procedure led to the disubstituted spiro deriv. III, an aza analog of perphydrohistrionicotoxin. [on SciFinder (R)]