Synthesis applications of aza-cope rearrangements

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).