Investigation of Lewis Acid-Carbonyl Solution Interactions via Infrared-Monitored Titration

Lewis acid-activation of carbonyl-containing substrates is broadly utilized in organic synthesis. In order to facilitate the development of novel reaction pathways and understand existing methods, it is necessary to determine the solution interactions between Lewis acids and Lewis bases. Herein, we report the application of in situ infrared spectroscopy and solution conductivity toward the identification of the solution structures formed when a range of carbonyl compounds are combined with catalytically active metal halide Lewis acids under synthetically relevant conditions. These data are consistent with formation of Lewis acid-dependent complexes, where metals of low relative Lewis acidity display no ground state interaction with carbonyls. Conversely, we observed the formation of polyligated complexes when stronger Lewis acids (SnCl4, TiCl4, ZrCl4, FeCl3, and AlCl3) were treated with ketones, aldehydes, and esters. This collection of observations is intended to assist the synthetic chemist in the design of new catalysts and the development of novel methods.