Asymmetric Synthesis of gem-Difluoromethylenated Dihydroxypyrrolizidines and Indolizidines

作者：Thaharn Watchara****; Bootwicha Teerawut; Soorukram Darunee; Kuhakarn Chutima; Prabpai Samran; Kongsaeree Palangpon; Tuchinda Patoomratana; Reutrakul Vichai; Pohmakotr Manat^*

来源：Journal of Organic Chemistry, 2012, 77(19): 8465-8479.

DOI：10.1021/jo301327s

An asymmetric synthesis of gem-difluoromethylenated dihydroxypyrrolizidines and indolizidines is described. The fluoride-catalyzed nucleophilic addition of PhSCF2SiMe3 (1) to chiral imides was achieved in satisfactory yields to provide mixtures of syn- and anti-isomers 6-9 with moderate to good diastereoselectivities. Reductive cleavage of the phenylsulfanyl group followed by intramolecular radical cyclization of the syn-isomers 6-9 occurred under refluxing conditions to afford the corresponding gem-difluoromethylenated 1-azabicyclic compounds 10-13 in moderate yields as a separable mixture of cis- and trans-isomers. The cis-isomers of compounds 10 and 12 and trans-13 were readily transformed to gem-difluoromethylenated dihydroxypyrrolizidines 20 and 27 and indolizidine 28, respectively, by reductive cleavage of the hydroxyl group and organometallic addition followed by hydrogenolysis.

• 出版日期2012-10-5