Our most recent collaboration with Pfizer and the Liu group at the University of Pittsburgh is now in press at ACS Catalysis. Methods to access small carbo- and heterocycles are of special importance in modern pre-clinical drug discovery and development owing the special properties of such motifs (conformationally restricted, low lipophilicity, etc.). In this project we developed a method to access substituted cyclopropyl boronic esters from benzylidene cyclopropanes (BCPs), which in turn can be made in a single step from benzaldehydes. While optimizing the reaction, we discovered an interesting effect of the ligand structure on pathway selectivity, and ultimately identified one ligand (BINAP) that could give almost exclusively ring-closed products, and another (dppe) that could give almost exclusively ring-opened products. To shed light on this phenomenon, our collaborators in the Liu group built a computational model that explains the observed reactivity trends. In terms of practical utility, we found the reaction to be compatible with a wide variety of azaheterocycles that are typically challenging to use in catalysis but are essential for medicinal chemists. Congratulation to all authors, particularly project co-leads Jose and Taeho.

For a link to the paper, click here: https://pubs.acs.org/doi/10.1021/acscatal.9b03557