Triply Convergent Ni-Electrocatalytic Assembly of 1,1-diaryl Cyclobutanes, Azetidines, and Oxetanes

05 November 2024, Version 1

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.

Keywords

Electrochemistry
Cross-Coupling
Nickel Catalysis
Radicals
Cyclobutane
Azetidine
Oxetane

Supplementary materials

Title
Description
Actions
Title
Supporting Information
Description
Experimental graphical procedures, additional experimental data, NMR characterization data and X-ray characterization detail.
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.