Aziridine-Allylsilane-Mediated Total Synthesis of (-)-Yohimbane.
A total asymmetric synthesis of (-)-yohimbane and ent-alloyohimbane is reported. The synthesis utilizes a novel aziridine-allylsilane cyclization reaction as a key step in the synthesis. Treatment of optically pure aziridine-allylsilane 16 with BF(3).OEt(2) provided a mixture of aminomethyl substituted carbocycles trans-20a and cis-20b in excellent yield and modest diastereoselectivity (trans/cis 3:1). Alkylation of the tosylamide followed by oxidation of the olefin in 20 provided the lactam 38, which was converted to (-)-yohimbane and ent-alloyohimbane by a Bischler-Napieralski reaction. The synthesis provided (-)-yohimbane in eight steps and 24% overall yield (from 16).
Bergmeier
Stephen C.
SC
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy and the Comprehensive Cancer Center, The Ohio State University, 500 West 12th Avenue, Columbus, Ohio 43210-1291.
Seth
Punit P.
PP