Alkylation of Ketene Silyl Acetals with Nitroolefins Mediated by Sterically Encumbered Lewis Acids

The utility of nitroolefins as "(+)C-C-NH(2)" and "(+)C(C=O)R" synthons is limited by their facile polymerization in the presence of nucleophiles. Although a number of procedures have been developed for the successful alkylation of ketones with nitroolefins, currently available procedures for the corresponding reaction of esters suffer from important limitations such as modest yields, lack of demonstrated generality, inconveniently low reaction temperatures, and/or the use of a large excess of one of the two reactants. In the present work, we examined the efficacy of a series of Lewis acid catalysts for the alkylation of ketene silyl acetals with nitroolefins. Previously reported conditions using diisopropoxytitanium dichloride failed to give satisfactory results with nitroolefins lacking a substituent alpha to the NO(2) group. In contrast, good to excellent results were obtained using sterically congested Lewis acids of the type pioneered by Yamamoto. The successful use of nitroethylene in this reaction represents a significant extension of the utility of this relatively unused "(+)CH(2)CH(2)NH(2)" synthon.