Zhai Huimin, Parvez Masood, Back Thomas G
Department of Chemistry, University of Calgary, Calgary, AB, Canada, T2N 1N4.
J Org Chem. 2007 May 11;72(10):3853-8. doi: 10.1021/jo0703101. Epub 2007 Apr 17.
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.
由L-丙氨酸衍生的γ-氯胺11与炔基砜12环化，通过共轭加成，随后相应砜稳定的阴离子进行分子内烷基化，得到脱氢哌啶19。19发生了意想不到的酸催化脱砜反应，一步通过烯胺部分的去硅基化和互变异构化为相应的醛，然后消除对甲苯亚磺酸。用氰基硼氢化钠对所得不饱和醛25进行高度立体选择性还原，得到非对映体比例>98:2的哌啶23。通过对23进行斯文氧化，随后进行维蒂希烯烃化和氢化/脱苄基反应，得到(-)-(对映体)-朱利弗洛里定(8)。
