Expanding the Chemical Space of 1,2-Difunctionalized Cyclobutanes
Anton V. Chernykh, Oleksandr V. Kudryk, Oleksandr S. Olifir, Alexey V. Dobrydnev, Едуард Б. Русанов, Виктория С. Москвина, Dmitriy M. Volochnyuk, Oleksandr O. Grygorenko
Abstract
An efficient approach to the synthesis of previously unavailable or hardly accessible 1,2-difunctionalized cyclobutanes (mostly with NH 2 /NHBoc, OH, SH, or SO 2 F groups attached to the carbocycle either directly or via a CH 2 unit) relying on the divergent strategy is described. This class of compounds provides sp 3 -enriched and conformationally restricted building blocks that are of special demand for medicinal chemistry. The target compounds were prepared not only as pure racemic (±)- cis - and (±)- trans -diastereomers but in some cases also as single enantiomers. The developed procedures are readily scaled up and allow obtaining the target compounds on an up to hundred-gram scale. On the basis of the results of 20 X-ray diffraction experiments, structural characterization of the 1,2-difunctionalized cyclobutane core was performed using the extended Cremer–Pople puckering parameters and exit vector (EVP) plots.