Asymmetric reduction of cyclic imines with chiral sodium acyloxyborohydrides

Abstract

Asymmetric reduction of prochiral cyclic imines with chiral sodium acyloxyborohydrides (5a–i), which are easily prepared by the reaction of NaBH₄ with various N-acyl α-amino-acids, has been investigated. Of these new reducing agents, triacyloxyborohydrides (5c–f), derived from NaBH₄(1 equiv.) and (S)-N-acylproline (3 equiv.), were found to reduce 3,4-dihydropapaverine (2) in tetrahydrofuran to (S)-norlaudanosine (3) hydrochloride in 60% optical yield. The N-benzyloxycarbonyl derivative (5c) could be isolated as a powder and characterized. The effect of solvents on this asymmetric reduction has been examined by the use of the isolated reagent (5c); halogenated alkane solvents such as CH₂Cl₂ or CHCl₂CH₃ gave a better optical yield of compound (3)(70% e.e.). The reagent (5c) also reduced other cyclic imines (6a–c) and (8) to the corresponding alkaloids (7a–c) and (9) in excellent optical yields (70–86% e.e.), providing an effective route to the asymmetric synthesis of these alkaloids. A possible reaction path for this reduction is also presented.