Divergent approach to the synthesis of (-)-balanol heterocycle and cis-3-hydroxypipecolic acid based on chiral 2-aminoalkanol equivalent

Abstract

Enantioselective synthesis of the hexahydroazepine core of (−)-balanol and formal synthesis of cis -3-hydroxypipecolic acid from a common intermediate have been accomplished by a divergent path. The common intermediate was accessed from a favorably protected enantiomerically pure 2-amino-1,3,4-butanetriol (ABT) equivalent via oxidation and Wittig olefination. The synthesis of (−)-balanol heterocycle featured tandem reduction/acetal-deprotection/γ-lactonization reaction and a one-pot azide reduction followed by seven membered aza-heterocycle formation while the route to cis -3-hydroxypipecolic acid highlighted the base induced piperidine ring formation and regioselective benzylidine-acetal cleavage. • Synthesis of piperidine/hexahydroazepine core is accomplished. • Benzylidene acetal is used as prominent chiral C4 building block. • Involves the tandem reduction/acetal deprotection/ γ -lactonization reaction.