Protecting-group-free catalytic asymmetric total synthesis of (-)-rosmarinecine

The protecting-group-free asymmetric total synthesis of (-)-rosmarinecine was achieved in only four steps from the commercially available (+/-)-3-hydroxypyrrolidine hydrochloride (2a). The key steps include the direct oxidation of (+/-)-2a to (+/-)-3-hydroxy-1-pyrroline N-oxide (1a) using the Davis reagent and the domino reaction: viz., the lipase-catalyzed dynamic kinetic resolution of (+/-)-1a with 1-ethoxyvinyl ethyl maleate followed by the intramolecular [3+2] dipolar cycloaddition reaction of the generated optically active ester. Some insights into the mechanism of the racemization of the optically active la, observed during the enzymatic process, were also obtained. (C) 2012 Elsevier Ltd. All rights reserved.