A highly stereoselective synthesis of (-)-(ent)-julifloridine from the cyclization of an alanine-derived chloroamine with an acetylenic sulfone.

Huimin Zhai, Masood Parvez, Thomas G Back

Department of Chemistry, University of Calgary, Calgary, AB, Canada, T2N 1N4.

The Journal of organic chemistry 2007 May 11

filter terms:

The cyclization of gamma-chloroamine 11, derived from l-alanine, and acetylenic sulfone 12 afforded the dehydropiperidine 19 via conjugate addition followed by intramolecular alkylation of the corresponding sulfone-stabilized anion. An unexpected acid-catalyzed desulfonylation of 19 occurred in one step via desilylation and tautomerization of the enamine moiety to the corresponding aldehyde, followed by elimination of p-toluenesulfinic acid. The highly stereoselective reduction of the resulting unsaturated aldehyde 25 with sodium cyanoborohydride produced piperidine 23 with a diastereomeric ratio of >98:2. (-)-(ent)-Julifloridine (8) was obtained by Swern oxidation of 23, followed by Wittig olefination and hydrogenation/debenzylation.

Citation

Huimin Zhai, Masood Parvez, Thomas G Back. A highly stereoselective synthesis of (-)-(ent)-julifloridine from the cyclization of an alanine-derived chloroamine with an acetylenic sulfone. The Journal of organic chemistry. 2007 May 11;72(10):3853-8