当前位置:科学网首页 > 小柯机器人 >详情
钯催化的N烯丙基胺与α芳基酮的对映选择性C(sp3)-HC(sp3)-H极反转偶联
作者:小柯机器人 发布时间:2021/11/26 14:04:23

中国科学技术大学龚流柱团队报道了钯催化的N烯丙基胺与α芳基酮的对映选择性C(sp3)–HC(sp3)–H极反转偶联策略。相关研究成果发表在2021年11月24日出版的《美国化学会杂志》。

C(sp3)–H键的不对称功能化能够以最小的功能基团操纵实现分子复杂性的精确组装,是实现多功能键形成事件的一种有吸引力但具有挑战性的策略。

该文中,研究人员报道了N-烯丙基胺和配位α-芳基羰基通过手性磷酰胺钯催化的不对称C(sp3)–H/C(sp3)–H umpolung偶联。多种α-杂芳基酮和2-酰基咪唑具有良好的耐受性,为高效合成具有高度区域和立体选择性的对映体富集的β-氨基-γ,δ-不饱和羰基衍生物开辟了一条方便和可调的途径,能够为不对称合成焦卡林提供关键中间体。

该方案展示了N-烯丙基胺通过协同质子和双电子转移过程裂解烯丙基C–H键的多峰反应性,有效地补充了已建立的烯丙基C–H功能化方法。计算研究和实验结果表明,α-杂芳基羰基和2-酰基咪唑攻击π-烯丙基钯物种的内球烯丙基化途径,其中氮与钯中心的配位使支化区域选择性优先。

附:英文原文

Title: Palladium-Catalyzed Enantioselective C(sp3)–H/C(sp3)–H Umpolung Coupling of N-Allylimine and α-Aryl Ketones

Author: Tian-Ci Wang, Ling Zhu, Shiwei Luo, Zhong-Sheng Nong, Pu-Sheng Wang, Liu-Zhu Gong

Issue&Volume: November 24, 2021

Abstract: Asymmetric functionalization of the C(sp3)–H bond is an attractive yet challenging strategy to achieve versatile bond-forming events, enabling the precise assembly of molecular complexity with minimal manipulation of functional groups. Here, we report an asymmetric C(sp3)–H/C(sp3)–H umpolung coupling of N-allylimine and coordinating α-aryl carbonyls by using chiral phosphoramidite-palladium catalysis. A wide variety of α-heteroaryl ketones and 2-acylimidazoles are nicely tolerated to open a convenient and tunable avenue for efficient synthesis of enantioenriched β-amino-γ,δ-unsaturated carbonyl derivatives with high levels of regio- and stereoselectivities, capable of providing a key intermediate for asymmetric synthesis of Focalin. This protocol showcases an umpolung reactivity of the N-allylimines through a concerted proton and two-electron transfer process to cleave the allylic C–H bond, effectively complementing established methodology for allylic C–H functionalization. An inner-sphere allylation pathway for both α-heteroaryl carbonyls and 2-acylimidazoles to attack the π-allylpalladium species is suggested by computational studies and experimental facts, wherein the nitrogen coordination to the palladium center enables the preference of branched regioselectivity.

DOI: 10.1021/jacs.1c10721

Source: https://pubs.acs.org/doi/10.1021/jacs.1c10721

 

期刊信息

JACS:《美国化学会志》,创刊于1879年。隶属于美国化学会,最新IF:14.612
官方网址:https://pubs.acs.org/journal/jacsat
投稿链接:https://acsparagonplus.acs.org/psweb/loginForm?code=1000