Radical cyclization of N-(cyclohex-2-enyl)-.alpha.,.alpha.-dichloroacetamides. Stereoselective syntheses of (.+-.)-mesembranol and (.+-.)-elwesine

• Published in: Journal of organic chemistry Vol. 56; no. 1; pp. 95 - 102
• Main Authors: Ishibashi, Hiroyuki, So, Taru Su, Okochi, Kyoko, Sato, Tatsunori, Nakamura, Nobuyuki, Nakatani, Hiroshi, Ikeda, Masazumi
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.01.1991; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; ALKALOID SYNTHESIS; AMARYLLIDACEAE ALKALOIDS; CIS-BICYCLO<4.2.0>OCTANONES; GENERAL METHODS; SCELETIUM ALKALOIDS; (+/-)-O-METHYLJOUBERTIAMINE; SYSTEMS; LACTAMS; MESEMBRINE; AZA-RING EXPANSION; Stereoselectivity; Alkaloid; Cyclization; Nitrogen heterocycle; Bicyclic compound; Racemate; Polycyclic compound; Aromatic compound; Free radical reaction; Total synthesis; Oxygen nitrogen heterocycle
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo00001a021

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.