A Continuous-Flow Approach to 3,3,3-Trifluoromethylpropenes: Bringing Together Grignard Addition, Peterson Elimination, Inline Extraction, and Solvent Switching
作者:Trevor A. Hamlin、Gillian M. L. Lazarus、Christopher B. Kelly、Nicholas E. Leadbeater
DOI:10.1021/op500190j
日期:2014.10.17
A continuous-flow approach to the synthesis of 3,3,3-trifluoromethylpropenes involving Grignard addition of, (trimethylsilyl)methylmagnesium chloride to a trifluoromethyl ketone followed by dehydrative desilylation of the alpha-trifluoromethyl-beta-hydroxysilyl alcohol using trimethylsilyl trifluoromethanesulfonate is reported. An inline aqueous/organic extraction and a concomitant solvent switch were key to the success of the methodology. Transition from batch to continuous flow conditions allows for higher yields, shorter reaction times, and facile scale out.