Triply Convergent Ni-Electrocatalytic Assembly of 1,1-diaryl Cyclobutanes, Azetidines, and Oxetanes, appearing today in @ChemRxiv :chemrxiv.org/engage/chemrxi… Increasingly complex, three-dimensional leads for drug discovery are testing the limits of modern organic synthesis. In this context, the need for new methods to access gem-diarylated cyclobutanes, azetidines, and oxetanes is apparent. The present study outlines a modular, scalable, chemoselective approach to solve this problem using simple alpha-bromoacids and aryl halides as intuitive starting materials. As demonstrated herein, a sequential series of Ni- electrocatalytic cross-couplings can be enlisted to enable rapid access to such structures, many of which have never been accessible before, without recourse to time-consuming polar bond disconnections that are inherently limiting in terms of accessible chemical space. The scalability of this new reaction sequence is demonstrated, alongside direct applications to known patented structures. A simple user guide is also presented to accelerate adoption of this strategy in medicinal chemistry. A super fun collaboration with BMS, Pfizer, Biogen, Enamine, and Abbvie.
