Abstract
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 a-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.
Supplementary materials
Title
Supporting Information
Description
Experimental graphical procedures, additional experimental data, NMR characterization data and X-ray characterization detail.
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