Highly Catalytic Allylation of Native Carbohydrates in Water with Indium: Kinetic, Mechanistic, and Spectroscopic Studies

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.