A highly stereoselective synthesis of (-)-(ent)-julifloridine from the cyclization of an alanine-derived chloroamine with an acetylenic sulfone.
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.
Zhai
Huimin
H
Department of Chemistry, University of Calgary, Calgary, AB, Canada, T2N 1N4.
Parvez
Masood
M
Back
Thomas G
TG
D000409:Alanine / Q000737:chemistry*; D000480:Alkynes / Q000737:chemistry*; D002700:Chloramines / Q000737:chemistry*; D003500:Cyclization; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000480:Alkynes; D002700:Chloramines; D010880:Piperidines; C509192:julifloridine; D000409:Alanine