Nucleophilic allylation reactions mediated by indium have served admirably, particularly in the Barbier-type allylation of unprotected carbohydrates in protic media. Allylations of aldehydes, ketones, and hydrazones that are catalytic in indium have been described with In(III), In(I), and indium metal and have been extended to native carbohydrates in our recently reported indium metal-catalyzed allylation using allylboronic acid pinacol ester (allylBpin). Whereas the mechanism of the Barbier-type allylation has been thoroughly investigated (albeit not with carbohydrate substrates), mechanistic studies of the catalytic reactions are scarce. In this report, we disclose detailed mechanistic investigations of the indium metal-catalyzed allylation of sugars in water/methanol mixtures, which reveal four critical aspects: (1) the true catalyst is a soluble In(III) species generated in trace quantities from the oxide/hydroxide layer on the indium metal surface under the reaction conditions, (2) the S-shaped kinetic profile observed with indium metal is explained by autoinduction as the combination of boric acid and the allylated product (1-allylsorbitol) lowers the reaction pH thereby increasing the concentration of soluble indium(III), (3) the active nucleophiles are monoallylindium(III) or diallylindium(III) intermediates (as characterized by 1H NMR and ESI-MS)-analogous to those formed under the classical Barbier-type allylation conditions, and (4) these two intermediates react with sugars at similar rates but with different diastereoselectivities. Finally, we demonstrated that a soluble indium(III) salt at very low loadings is catalytically competent and does not exhibit autoinduction.
Albritton et al. (Thu,) studied this question.