Asymmetric Suzuki-Miyaura coupling of heterocycles via Rhodium-catalysed allylic arylation of racemates

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. Asymmetric Suzuki-Miyaura procedures often have difficulty incorporating heterocyclic reagents, despite the importance of these in the pharmaceutical industry. Here the authors report a rhodium catalysed cross-coupling that tolerates a wide variety of nucleophiles including a range of heterocycles.