Catalytic Intramolecular Conjugate Additions of Aldehyde-Derived Enamines to α,β-Unsaturated Esters
Catalytic Intramolecular Conjugate Additions of Aldehyde-Derived Enamines to α,β-Unsaturated Esters
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DOI：
10.1021/acs.orglett.0c01666
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发表时间：
2020-06-05
期刊：
影响因子：
5.2
通讯作者：
Gellman, Samuel H.
中科院分区：
文献类型：
--
作者：
Girvin, Zebediah C.;Lampkin, Philip P.;Gellman, Samuel H.
我们报告了一对已知的催化剂，使分子内共轭加成衍生的烯胺的α，β-不饱和酯。尽管广泛的先前探索的共轭加成衍生的烯胺，催化共轭加成未活化的烯酸酯是前所未有的。实现对映选择性和非对映选择性的六元环形成需要手性吡咯烷的协调作用，用于通过烯胺形成亲核活化醛，和氢键供体，用于亲电活化烯酸酯。氢键供体的适当选择对于化学选择性是必不可少的，这需要最小化来自高醛醇反应的竞争。在由环庚烯合成（-）-育亨烷的六步反应中证明了该方法的实用性。
We report a pairing of known catalysts that enables intramolecular conjugate additions of aldehyde-derived enamines to alpha,beta-unsaturated esters. Despite extensive prior exploration of conjugate additions of aldehyde-derived enamines, catalytic conjugate additions to unactivated enoate esters are unprecedented. Achieving enantioselective and diastereoselective six-membered ring formation requires the coordinated action of a chiral pyrrolidine, for nucleophilic activation of the aldehyde via enamine formation, and a hydrogen bond donor, for electrophilic activation of the enoate ester. Proper selection of the hydrogen bond donor is essential for chemoselectivity, which requires minimizing competition from homoaldol reaction. Utility is demonstrated in a six-step synthesis of (-)-yohimbane from cycloheptene.