Organocatalytic vinyl and friedel-crafts alkylations with trifluoroborate salts

Friedel-Crafts alkylation is a well known chemical reaction and is extremely useful in carbon-carbon bond formation between an alkyl and an aromatic system. However, this classical type of coupling is limited by the preponderance of unwanted side reactions such as rearrangement, multiple substitution, and deactivation of the substrate to further functionalization. In this report, an iminium ion-catalyzed approach was developed for the activation of -neutral and even π-deficient nucleophiles for conjugate addition of vinyl and heteroaryl trifluoroborate adducts to enals led to alkylated products with high yields and enantioselectivity. Preliminary screens on the structure of amines showed the best stereocontrol and conversion by using a tryptophan derivative of imidazolidinone as catalyst in 1,2-dimethoxyethane (DME) (Table 1). The same conditions were adopted to determine the effects of various alkyl trifluoroborates and further extended to different α, β-unsaturated aldehydes, resulting in excellent yield and enantioselectivity. This study accounts the first use of trifluoroalkylborates and an iminium activation for enantioselective conjugation to α, β-unsaturated aldehydes.