First asymmetric synthesis of a C2-symmetric 2- endo,6- endo-disubstituted bispidine

Abstract

The enantioselective synthesis of a C 2-symmetric 2- endo,6- endo-disubstituted bispidine (3,7-diazabicyclo[3.3.1]nonane) has been accomplished for the first time. The key step was a Michael addition of the protected β-amino ester methyl ( R)-3-{ N-benzyl- N-[( S)-1-phenylethyl]amino}-3-phenylpropionate to its α-methylene derivative delivering an anti, anti-configured α,α′-methylene-bridged bis(β-amino ester) as the major diastereomer. Deprotection, reduction and cyclisation furnished (1 R,2 R,5 R,6 R)-2,6-diphenyl-3,7-bis(( S)-1-phenylethyl)-3,7-diazabicyclo[3.3.1]nonane in six steps and 15% overall yield.