Improvements in Distereoselectivity of Perfluoroalkylations

A Ru-catalyzed direct trifluoromethylation of N-acyloxazolidinones has been developed. The experimentally simple reaction uses inexpensive reagents while providing moderate to high yields with good stereocontrol. Studies show compatability with various functional groups, aromatics, and certain heteroaromatic substituents. Seeking to improve the diastereoselectivity of α-trifluoromethylation, N-acyloxazolidinones are being synthesized with more steric bulk using amino acids L-valine and phenyl glycine as starting materials. L-valine was subjected to Fisher esterification, followed with boc protection of the primary amine. Grignard addition to the ester provided the corresponding alcohol, which underwent cyclization to form an Evan’s-type auxiliary in high yields. The auxiliary will be acylated with hexanyl chloride to deliver N-acyloxazolidinone that is to be trifluoromethylated. Employing reaction conditions previously reported, the new auxiliaries will be tested to determine if diastereotopic ratios can be improved. Enhancements in diastereoselectivity are an important goal in order to increase the amount of the desired diastereomer synthesized, which will be useful for both academic and industrial applications. The descriptions that follow explain a method for a convenient synthesis for the fluorinated material.