RADICAL CYCLIZATION OF N-(CYCLOHEX-2-ENYL)-ALPHA,ALPHA-DICHLOROACETAMIDES - STEREOSELECTIVE SYNTHESES OF (+/-)-MESEMBRANOL AND (+/-)-ELWESINE

Stereoselective syntheses of the Sceletium alkaloid (+/-)-mesembranol (2) and the Amaryllidaceae alkaloid (+/-)-elwesine (3) have been achieved. A key step in the syntheses involves the Bu3SnH-mediated radical cyclization of the dichloroacetamides 34 and 46, which provides the cis-3a-aryloctahydroindolones 36 and 47, respectively. The amides 34 and 46 were prepared in a highly stereocontrolled manner from the corresponding 1-arylcyclohexenes 29 and 41 along the lines: 29 --> 30a --> 31 --> 32 --> 33 --> 34 and 41 --> 42a --> 44a --> 45a --> 46. Transformation of 36 into (+/-)-mesembranol was readily accomplished by reduction with diborane and subsequent removal of the O-benzyl protecting group by hydrogenolysis over Pd/C. On the other hand, debenzylation of 36 with Raney Ni afforded a mixture of the 6-alpha- and 6-beta-alcohols 39a and 39b, which was then reduced by alane to give a separable mixture of (+/-)-mesembranol and (+/-)-6-epimesembranol (40). Reduction of 47 with diborane followed by catalytic hydrogenolysis over Pd/C afforded the amino alcohol 50, which has already been converted into (+/-)-elwesine by Pictet-Spengler cyclization.