Stereocontrolled Synthesis of 1,2-Dialkyl-4-halopyrrolidines through PhSeX-Induced Cyclization of Secondary Homoallylamines

Abstract

The selenium-induced cyclization of α-alkyl or α,α-dialkyl-homoallyl-benzylamines 1 by use of PhSeX (X = Cl, Br, I; 1.5 equiv.) provided a mixture of (phenylselanylmethyl)azetidines 2 and (phenylselanyl)pyrrolidines 3.1 When an excess of PhSeX (X = Cl, Br) was used, 4-halopyrrolidines 4 (X = Cl) or 5 (X = Br) were formed and isolated in very good yields. Mono- or dialkyl 4-halopyrrolidines 4 and 5 could also be obtained stereospecifically by SO2Cl2 or Br2 treatment of 4-(phenylselanylmethyl)azetidines 2, by way of the intermediate (halomethyl)azetidines 14 (X = Cl) or 15 (X = Br). When starting from 4-(phenylselanyl)pyrrolidines 3, monoalkylated 4-halopyrrolidines 4 or 5 could be obtained stereospecifically after decomposition of the unstable dihaloselenuranes 16 and 17. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)