An efficient, stereoselective synthesis of (-)-bulgecinine from (S)-aspartic acid

Article abstract of DOI:10.1016/S0957-4166(97)00215-2

A stereoselective synthesis of (2S,4S,5R)-4-hydroxy-5-hydroxymethylproline 1 starting from (S)-aspartic acid 2 is described. The key step of the synthesis is the [Rh(OAc)₂]₂ catalyzed stereospecific transformation (de >98%) of the hexafluoroacetone protected diazoketone 5 into the 4-oxoproline derivative 7. The keto function of 7 was reduced with high diastereoselectivity (de >88%) to give the 4-cis-hydroxyproline derivative 8. After deprotection (-)-bulgecinine 1 was obtained from 9 on reduction of the ester moiety with LiBHEt₃.