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

A stereoselective synthesis of (2S,4S,5R)-4-hydroxy-5-hydroxymethylproline1 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.

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