REGIOSELECTIVE AND STEREOSELECTIVE FUNCTIONALIZATION OF AN OPTICALLY-ACTIVE TETRAHYDROINDOLIZINE DERIVATIVE - CATALYTIC ASYMMETRIC SYNTHESES OF LENTIGINOSINE, 1,2-DIEPILENTIGNOSINE, AND GEPHYROTOXIN-209D

To demonstrate the usefulness of optically active 3,5,8,8a-tetrahydro-5-oxoindolizine (9) which is prepared by the catalytic asymmetric Heck-type cyclization, regio- and stereoselective functionalizations of(S)- and (R)-9 have been examined. Stereoselective epoxidation of 3,5,6,7,8,8a-hexahydro-5-oxoindolizine (10) obtained by the regioselective reduction was examined, and it was found that electrophile (peracid or bromonium cation) reacted from the opposite side of C-8a-H in a highly stereoselective manner. The catalytic asymmetric syntheses of lentiginosine (3) and 1,2-diepilentiginosine (4) using these stereoselective epoxidations have been achieved. Dihydroxylation of(S)-9 catalyzed by OsO4 gave (6R,7R,8aS)-3,5,6,7,8,8a-hexahydro-6,7-d (16) regio- and stereoselectively. Several other functionalizations and a synthesis of gephyrotoxin 209D (6) are also described. The origin of the high stereoselectivity observed in the functionalization of 9 is discussed based on the stereoelectronic principle such as the Cieplak model.