CHEMICAL SCIENCE

Chinese scientists have made new breakthroughs in the three-dimensional convergence asymmetric cross-coupling reaction


On May 26, 2022, the team of Professor Liu Xinyuan of Southern University of Science and Technology and the team of Professor Hong Xin of Zhejiang University published a new research paper in Nature Chemistry entitled “Mechanism-based ligand design for copper-catalysed enantioconvergent C(sp3)–C(sp) cross-coupling of tertiary electrophiles with alkynes”。

The research group successfully realized the three-dimensional convergence asymmetric cross-coupling reaction of racemic non-cyclic tertiary alkyl halogenated hydrocarbons and terminal alkyne hydrocarbons, and directly and efficiently and highly enantioselectively constructed a series of compounds containing non-cyclic chiral seasonal carbon centers.

Cross-coupling is one of the most efficient ways to construct carbon-carbon bonds, and the 2010 Nobel Prize in Chemistry was awarded to three scientists who have made outstanding contributions to the field. In recent years, with the development of asymmetric catalysis and 3D transition metal catalysis, the C(sp3)–C(sp) cross-coupling reactions involving haloalkanes, especially the more challenging asymmetric cross-coupling, have gradually become a hot topic of concern for chemists. So far, however, there have been few reports of the construction of non-cyclic seasonal carbon chiral centers by stereoglupolytic cross-coupling reactions of tertiary haloalkanes.

Sonogashira coupling is an important method for constructing alkyne compounds. In 2019, Professor Liu Xinyuan’s team successfully developed a single-electron catalytic system composed of monovalent copper and chiral three-tooth anion N, N, P-ligands, which realized the asymmetric Sonogashira cross-coupling reaction of racemic secondary haloalkanes and teltynes by effectively regulating the reducing and stereoscopic environment of copper. Chem. 2019, 11,1158)。

Recently, the team cooperated with Professor Hong Xin of Zhejiang University, based on theoretical calculations and chiral ligand design, developed chiral three-tooth anion N, N, N-ligand with a small hindrance coordination center and a long-sided arm effect, solved the chiral control problem of tertiary alkyl radicals, successfully realized the three-dimensional convergence asymmetric cross-coupling reaction of race-neutral non-cyclic tertiary alkyl halocarbons and terminal alkyne hydrocarbons, and directly and efficiently and highly enantioselimilatedly constructed a series of compounds containing non-cyclic chiral seasonal carbon centers. Mechanism studies and DFT calculations show that the cross-coupling reaction involving secondary radicals is significantly different, and tertiary alkyl radicals directly form C–C bonds by radical substitution.

The successful development of such N, N, N-ligands provides a practical new strategy for the development of copper-catalyzed asymmetric synthesis of chiral seasonal carbon centers involving tertiary alkyl radicals. This method can achieve a variety of post-transformation processes and provide an effective platform for rapid construction of C(sp3)–C(sp)/C(sp2)/C(sp3) chemical bonds, which fully illustrates the practicality of the method. (Source: Science Network)

Related paper information:https://doi.org/10.1038/s41557-022-00954-9



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