Visible light-induced cobalt-catalyzed radical coupling builds axial chirality

Recently, Professor Xiao Wenjing and Professor Lu Liangqiu’s team from Central China Normal University published a latest research report entitled “Construction of axial chirality via asymmetric radical trapping by cobalt under visible light” at Nature Catalysis.

Through a synergistic visible-cobalt catalytic strategy, the research team achieved the dynamic kinetic asymmetric transformation of racemic heteroaryl compounds for the first time by using asymmetric radical coupling reactions. Professor Xiao Wenjing and Professor Lu Liangqiu are the corresponding authors of the paper, doctoral students Jiang Xuan and Xiong Wei are the co-first authors, and Central China Normal University is the first unit to complete the paper.

As a green and sustainable emerging strategy, visible photocatalysis is widely used in the field of organic synthesis. Since the reaction often involves highly active free radical intermediates, there are still some challenges in their enantioselective control. In view of this problem, organic chemists combined asymmetric organic catalysis, transition metal catalysis, enzyme catalysis (Figure 1a) and other stereoscopic control strategies to develop an effective asymmetric visible light catalysis strategy. Although the field has been rapidly developed in recent years, it is mainly used for the synthesis of central chiral compounds, and the construction of other chiral skeletons is still in its infancy. In 2018, Professor Bach of the Technical University of Munich used chiral bifunction photocatalysts to achieve the first visible light-induced racemic six-membered lactam bilateral demicration reaction (Figure 1b, Nature 2018, 564, 240-243). Since then, the photocatalytic asymmetric synthesis of other axial chiral skeletons has rarely been reported.

Xiao Wenjing and Lu Liangqiu’s team at Central China Normal University has long been committed to the study of asymmetric catalysis induced by visible light. In the previous study, the research team combined visible light catalysis and cobalt catalysis to develop an asymmetric radical addition reaction (Angew. Chem. Int. Ed. 2019, 58, 13375-13379) and asymmetric reduction of aryl halides (J. Grignard-type addition) and aryl halides Am. Chem. Soc. 2022, 144, 8347-8354)。 In this work, they developed a novel photo/cobalt synergistic catalytic strategy that achieves the dynamic kinetic asymmetric transformation of racemic heteroaryl compounds. The key to the success of this reaction lies in the formation of axle chiral aryl cobalt species after oxidation addition due to the coordination of pyridine, reducing the rotational energy barrier, race cancellation occurs, and then stereoselectively captures the free radicals produced by photocatalysis (Figure 1c).

Figure 1: Study background and reaction design

To verify the feasibility of this strategy, the authors systematically optimized the reaction conditions by using racemic bizylar trifluoromethanesulfonate and benzyl Hans ester as model reactions. Experimental results show that the chiral multi-tooth ligand developed by Professor Zhang Junliang’s research groupL8(Angew. Chem. Int. Ed. 2015, 54, 14853-14857; This type of chiral ligand used in this study was provided free of charge by Suzhou Kairoli New Material Technology Co., Ltd., and the author expresses special thanks) plays a crucial role in the stereoselective control and reaction efficiency of the process. Under optimal conditions, the authors examined the substrate range. The results show that for different electrical aryl groups, heteroaryl substituted bizyryl trifluoromethanesulfonate and Hans ester substrates, the coupling reaction can obtain relatively good results (Figure 2). In addition, for asymmetric reduction coupling catalytic systems, the reaction also has good compatibility with benzyl halides, and a series of biaryl axonic chiral products containing isoquinoline skeletons are generally obtained with high enantioselectivity (Figure 3).

Figure 2: Range of asymmetric radical coupling reactions (racemic bisaryl trifluoromethanesulfonate with benzyl Hans ester)

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Figure 3: Asymmetrical reduction cross-coupling range (racemic bisariaryl trifluoromethanesulfonate versus haloalkanes)

After that, the authors also verified the practicality of the methodology. Through a simple hydrazine lysis reaction, axal chiral primary amine compounds can be obtained, which continue to synthesize a series of bifunctional thiourea catalysts and multi-tooth ligands at moderate to excellent yields. In addition, the authors found that such axle chiral products generally have a aggregation-induced luminescence effect. Obtained by further modificationMe-3kIt has excellent circular polarization luminescence properties, and its luminescence asymmetry factor | gum | of 3.02×10-2 (the test work was completed by the team of researchers Liu Minghua of the Institute of Chemistry of the Chinese Academy of Sciences, and the author expressed special gratitude). At the same time, in collaboration with Professor Qi Xiaotian of Wuhan University, the author conducted an in-depth study of the reaction mechanism using theoretical calculations, control experiments and high-resolution mass spectrometry.

In summary, the Xiao Wenjing/Lu Liangqiu team developed the first visible light-induced asymmetric cobalt catalytic radical coupling reaction, realized the dynamic kinetic asymmetric conversion of race-canceling heteroaryl compounds, prepared a series of axial chiral heteroaryl compounds with excellent enantioselectivity, and studied the optical properties of related compounds. This study not only provides new ideas for light/cobalt synergistic catalysis of asymmetric radical coupling reactions, but also provides new methods for synthesizing axial chiral heteroaryl backbones and related functional materials. (Source: Science Network)

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