Synthesis applications of aza-cope rearrangements : A stereoselective synthesis of 9a-arylhydrolilolidines [and a new approach to the synthesis of aspidosperma] alkaloids

Abstract A “Mannich-directed” 2-azonia-[3,3]-sigmatropic rearrangement is the key step in a new, completely stereoselective, method for preparing 9a-arylhydrolilolidines. Specifically, cis -fused bicyclic aminoalcohols 24 upon treatment with formaldehyde and acid afford hydrolilolidines 25 in a single step and in excellent yield. The complete stereoselectivity of this “ring-enlarging pyrrolidine annulation” reaction follows stereorationally from the trans -relationship of vinyl and amine functions in the bicyclic precursor 24 (eqn 6).