Stereoselective synthesis of (3S,4S)-tert-butyl-N-Boc-3-ethyl-4-hydroxy-l-prolinate and (3S,4R)-tert-butyl-N-Boc-3-ethyl-4-hydroxy-l-prolinate

Diastereomers of tert-butyl-N-Boc-3-ethyl-4-hydroxy-l-prolinate 1 and 2 have been synthesized in six steps starting from readily available Boc-protected trans-4-hydroxy-l-proline. The key reactions in the synthesis are asymmetric reductions, firstly on the 4-ketoproline intermediate 6 and secondly on the 3-exocyclic olefin bond of the resulting allylic alcohol 7 or 8. Reaction conditions were optimized in order to control the stereochemistry of the three chiral centers.