Domino Synthesis of Bicyclic 3,5-Anhydro Furanose Mimics Using a Binary Al(III) Complex/Halide Catalyst

Structurally diverse heterobicyclic
diethers can be conveniently
accessed in good yields through a catalytic domino process that is
controlled by a versatile binary catalyst comprising an Al­(III) aminotriphenolate
complex and a bromide salt. These bicycles, representing non-natural,
3,5-anhydro furanose mimics, are derived from bis-epoxy substrates
through a double cyclization pathway that is initiated by the activation
of the free alcohol in the precursor compounds. Various mechanistic
control experiments, X-ray analyses, and computational investigations
allowed us to rationalize the intricacies of this multistep process
and the role of each catalyst component while revealing a clear preference
for a sequence that starts with oxetane ring formation followed by
an annulation step forming a fused and substituted tetrahydrofuran.