Alkynylogation and transformative fluorination in synthesis

University Of Louisville Research Foundation Inc, Louisville KY

Investigators

Abstract

This award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports Professor Frederick Luzzio at the University of Louisville to investigate alkynylogation in order to promote the transmission of electronic effects between a nucleophilic or electrophilic center through the intermediacy of a triple bond, and the conversion of hydrofluorocarbons (HFCs) into functionalized fluorinated building blocks through C-F activation of some fluorines within the molecule. The alkynylogation effects will be studied using a triple bond extended aldol (alkynylogous aldol) reaction as a working model, utilizing modern synthetic tools capable of controlling the regio- and stereochemistry. Specifically, the effect of size and Lewis acidity of the cation counterion of a base on the gamma-directed alkynylogous aldol reaction will be investigated; the effects of Lewis acid on the regio- and stereoselectivity of Mukaiyama type alkynylogous aldol reaction, and the reaction of silylketene acetals with electrophiles. Transformative fluorination will be pursued through the functionalization of industrially available, ecologically benign, three- or four-carbon HFCs by selectively removing fluorine, utilizing C-F bond activation reactions. A second generation of difluoropropargyl synthons will also be developed utilizing environmentally friendly reagents and conditions, capable of engendering cyclic precursors fitted with synthetic handles that maximize structural diversity. This research aims for practical approaches, and environmentally friendly uses of materials and for organic synthesis. The project will train a younger generation of chemists in synthesis and organofluorine chemistry and advance the education of underrepresented minorities.