英国牛津大学Fletcher, Stephen P.团队报道了螯合作用使非环烯丙基系统上对映转化剂Suzuki–Miyaura交叉偶联的选择性得以控制。相关研究成果于2024年2月8日发表于国际顶尖学术期刊《自然—化学》。

与芳基硼酸和烯丙基亲电试剂的不对称Suzuki–Miyaura交叉偶联，是将外消旋混合物转化为对映体富集产物的有力方法。目前，对映转化烯丙基芳基化仅限于关于烯丙基单元对称的底物，并且缺乏控制非环烯丙基系统中的区域-、E/Z-和对映选择性的策略是一个主要限制。

该文中，使用能够共轭加成或烯丙基芳基化的系统，研究人员发现了允许无环系统进行化学和区域选择性、对映转化的烯丙基Suzuki–Miyaura型芳基化反应的结构特征和实验条件。可以使用各种各样的硼酸偶联配偶体，并且在烯丙基单元上可以容忍烷基和芳香族取代基，从而可以获得各种各样的结构。

初步的机理研究表明，酯基的螯合能力对于获得高的区域选择性和对映选择性至关重要。利用该方法，研究人员能够合成天然产物（S）-姜黄烯和（S）-4，7-二甲基-1-四酮以及临床上使用的抗抑郁药舍曲林（Zoloft）。

附：英文原文

Title: Chelation enables selectivity control in enantioconvergent Suzuki–Miyaura cross-couplings on acyclic allylic systems

Author: Stojalnikova, Violeta, Webster, Stephen J., Liu, Ke, Fletcher, Stephen P.

Issue&Volume: 2024-02-08

Abstract: Asymmetric Suzuki–Miyaura cross-couplings with aryl boronic acids and allylic electrophiles are a powerful method to convert racemic mixtures into enantioenriched products. Currently, enantioconvergent allylic arylations are limited to substrates that are symmetrical about the allylic unit, and the absence of strategies to control regio-, E/Z- and enantioselectivity in acyclic allylic systems is a major restriction. Here, using a system capable of either conjugate addition or allylic arylation, we have discovered the structural features and experimental conditions that allow an acyclic system to undergo chemo- and regioselective, enantioconvergent allylic Suzuki–Miyaura-type arylation. A wide variety of boronic acid coupling partners can be used, and both alkyl and aromatic substituents are tolerated on the allylic unit so that a wide variety of structures can be obtained. Preliminary mechanistic studies reveal that the chelating ability of the ester group is crucial to obtaining high regio- and enantioselectivity. Using this method, we were able to synthesize the natural products (S)-curcumene and (S)-4,7-dimethyl-1-tetralone and the clinically used antidepressant sertraline (Zoloft).

DOI: 10.1038/s41557-023-01430-8

Source: https://www.nature.com/articles/s41557-023-01430-8