厦门大学霍浩华团队报道了Ni/光氧化还原催化α-溴苯甲酸酯与醛的对映选择性酰化——醛-醛交叉偶联的正式方法合成挑战。相关研究成果发表在2024年6月12日出版的《美国化学会杂志》。

相同或相似官能团的催化交叉偶联是碳-碳键形成的基石策略，如著名的方法，烯烃交叉复分解、Kolbe电解和各种亲电交叉偶联。然而，偶联醛（有机合成的基本组成部分）的类似方法仍然不成熟。虽然1832年首次报道的安息香型缩合为醛二聚提供了可靠的途径，但不相同但相似的醛的化学和对映选择性交叉偶联仍然是一个未解决的挑战。

该文中，研究人员报道了一个统一的平台，能够实现醛的高度化学和对映选择性交叉偶联。通过利用镍光氧化还原催化与每种醛的离散活化策略相结合，这种机制上不同的方法促进了醛衍生的α-氧自由基，与由不同的醛光催化产生的酰基的对映选择性结合。这一新策略使人们能够模块化地获得具有两个最小分化脂族取代基的对映体富集的α-氧化酮，这是现有化学催化或生物催化技术无法实现的。

该方法在各种药物相关分子的流线型不对称合成中的应用证明了其合成的实用性。此外，机理研究合理化了镍光氧化还原催化的多功能性，以开发新的途径来解决长期存在的合成挑战。

附：英文原文

Title: Ni/Photoredox-Catalyzed Enantioselective Acylation of α-Bromobenzoates with Aldehydes: A Formal Approach to Aldehyde-Aldehyde Cross-Coupling

Author: Chengyang Li, Junliang Cheng, Xiang Wan, Jian Li, Weisai Zu, Yumin Xu, Yongliang Huang, Haohua Huo

Issue&Volume: June 12, 2024

Abstract: The catalytic cross-coupling of identical or similar functional groups is a cornerstone strategy for carbon–carbon bond formation, as exemplified by renowned methods, such as olefin cross-metathesis, Kolbe electrolysis, and various cross-electrophile couplings. However, similar methodologies for coupling aldehydes─fundamental building blocks in organic synthesis─remain underdeveloped. While the benzoin-type condensation, first reported in 1832, offers a reliable route for aldehyde dimerization, the chemo- and enantioselective cross-coupling of nonidentical yet similar aldehydes remains an unsolved challenge. Herein, we report a unified platform enabling highly chemo- and enantioselective cross-coupling of aldehydes. By leveraging nickel photoredox catalysis in tandem with discrete activation strategies for each aldehyde, this mechanistically distinct approach facilitates the enantioselective union of an aldehyde-derived α-oxy radical with an acyl radical, photocatalytically generated from a distinct aldehyde. This novel strategy enables modular access to enantioenriched α-oxygenated ketones with two minimally differentiated aliphatic substituents, a feat not achievable with existing chemocatalytic or biocatalytic techniques. The synthetic utility of this method is demonstrated by its application in the streamlined asymmetric synthesis of various medicinally relevant molecules. Additionally, mechanistic investigations rationalize the versatility of nickel photoredox catalysis to exploit new pathways for addressing long-standing synthetic challenges.

DOI: 10.1021/jacs.4c03164

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c03164