Abstract
Using asymmetric catalysis to simultaneously form carbon–carbon bonds and generate single isomer products is strategically important. Suzuki-Miyaura cross-coupling is widely used in the academic and industrial sectors to synthesize drugs, agrochemicals and biologically active and advanced materials. However, widely applicable enantioselective Suzuki-Miyaura variations to provide 3D molecules remain elusive. Here we report a rhodium-catalysed asymmetric Suzuki-Miyaura reaction with important partners including aryls, vinyls, heteroaromatics and heterocycles. The method can be used to couple two heterocyclic species so the highly enantioenriched products have a wide array of cores. We show that pyridine boronic acids are unsuitable, but they can be halogen-modified at the 2-position to undergo reaction, and this halogen can then be removed or used to facilitate further reactions. The method is used to synthesize isoanabasine, preclamol, and niraparib—an anticancer agent in several clinical trials. We anticipate this method will be a useful tool in drug synthesis and discovery.
Highlights
Using asymmetric catalysis to simultaneously form carbon–carbon bonds and generate single isomer products is strategically important
We previously reported catalytic asymmetric addition of nucleophiles to racemic allylic halide starting materials[34,35,36,37] including a system for boronic acid addition[30] involving [Rh(cod)(OH)]2 and (S)-Xyl-P-PHOS in the presence of Cs2CO3
We show that a class of cross-coupling partners that do not undergo reaction can be coerced into cross-coupling by introducing a halogen to the core
Summary
Using asymmetric catalysis to simultaneously form carbon–carbon bonds and generate single isomer products is strategically important. We report a rhodium-catalysed asymmetric Suzuki-Miyaura reaction with important partners including aryls, vinyls, heteroaromatics and heterocycles. In particular the Suzuki-Miyaura reaction, which involves cross-coupling between an sp2-hybridized boronic acid and an sp2-hybridized halide, is robust and highly tolerant of varying the reaction partners.
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