Copper-Catalyzed Hydroboration to access cyclopropyl boronates: pre-print online

Appearing online today in ChemRxiv is a pre-print describing a collaboration with Pfizer’s Oncology Medicinal Chemistry group and with Prof. Peng Liu’s computational organic chemistry lab. With Pfizer, we continue to work together develop new catalytic methods to access strained carbo- and heterocycles. With the Liu group, we team up to study mechanism and ligand effects in catalytic alkene addition chemistry. In the latest story to emerge from these efforts, we report that benzylidene cyclopropanes (BCPs), which can be prepared from benzaldehydes in a single step by Wittig olefination, can undergo pathway-selective hydroboration under the action of a copper-bisphosphine catalyst. Depending on the structure of the phosphine ligand, two divergent product outcomes can be obtained, with the cyclopropane opening via β-carbon elimination or remaining intact. Though Lewis basic heterocycles often inhibit catalysis with late transition metals, this is not the case here, as the tolerance for a wide variety of pyridines, quinolines, etc., is generally excellent. This is makes it well-suited for use in pre-clinical drug discovery and development. Thanks to our collaborators at Pfizer for helping us develop and field-test this method, and to our collaborators in the Liu lab for invaluable insight regarding the role of the ligand in dictating pathway selectivity. For a link to the pre-print, click here.)