Preparation of Chiral Allenes through Pd-Catalyzed Intermolecular Hydroamination of Conjugated Enynes: Enantioselective Synthesis Enabled by Catalyst Design
Preparation of Chiral Allenes through Pd-Catalyzed Intermolecular Hydroamination of Conjugated Enynes: Enantioselective Synthesis Enabled by Catalyst Design
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DOI：
10.1021/jacs.9b02637
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发表时间：
2019-05-29
影响因子：
15
通讯作者：
Malcolmson, Steven J.
中科院分区：
文献类型：
--
作者：
Adamson, Nathan J.;Jeddi, Haleh;Malcolmson, Steven J.
在这项研究中，我们建立了共轭烯炔在钯催化下选择性的1，4-氢胺化反应，以提供带有侧链烯丙基胺的手性烯丙烯。几个伯基和仲基脂肪族和芳基取代胺与广泛的单取代和双取代烯炔在非对映选择性反应中偶联，其中DPEphos作为Pd的配体。二苯甲酮亚胺作为氨替代品，在两步/一锅工艺中提供伯胺。对手性催化剂的研究表明，C-N键的形成具有高度的可逆性，这对对映体选择性产生了负面影响。因此，开发了一种电子贫乏的二茂铁基-PHOX配体，以实现高效的对映选择性烯炔氢胺化反应。
In this study, we establish that conjugated enynes undergo selective 1,4-hydroamination under Pd catalysis to deliver chiral allenes with pendant allylic amines. Several primary and secondary aliphatic and aryl-substituted amines couple with a wide range of mono- and disubstituted enynes in a nonenantioselective reaction where DPEphos serves as the ligand for Pd. Benzophenone imine acts as an ammonia surrogate to afford primary amines in a two-step/one-pot process. Examination of chiral catalysts revealed a high degree of reversibility in the C-N bond formation that negatively impacted enantioselectivity. Consequently, an electron-poor ferrocenyl-PHOX ligand was developed to enable efficient and enantioselective enyne hydroamination.