A METHOD FOR DIASTEREOSELECTIVE TRIFLUOROMETHYLATIONS
Authors:Aaron Herrmann, Elias Picazo
Mentor:Armen Zakarian, Professor of Chemistry, University of California Santa Barbara
Due to their unique physical properties, fluorinated compounds have been shown to be beneficial in a wide variety of fields. The electronegativity, small atomic radius, and binding properties of fluorine make these compounds useful in materials, agriculture, and pharmaceutical research. N-acyloxazolidinones are cyclic molecules that have been used by the Zakarian group to direct the stereochemistry of perfluoroalkylations, the attachment of long carbon chains saturated with fluorine. The reaction uses inexpensive reagents while providing moderate to high yields with good stereocontrol for almost all perfluoroalkylations. Studies show compatability with various functional groups, aromatics, and heteroaromatic substituents. However, these reactions lack strong stereocontrol for trifluoromethylations, the smallest sized perfluoroalkylation. Seeking to improve the diastereoselectivity of α-trifluoromethylations this past summer, the N-acyloxazolidinone was synthesized with more steric bulk using amino acid L-valine as the starting material. The five-step synthesis has successfully transformed L-valine into an Evan’s-type auxiliary and acylated in high yields. Employing reaction conditions similar to those used by the Zakarian group, the improved auxiliaries have increased diastereotopic ratios, increased the reaction yields, and have reduced the amount of time and catalytic loading required for completion. 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.