On the regioselectivity of the Hanessian–Hullar reaction in 4,6-O-benzylidene protected galactopyranosides

The N-bromosuccinimide mediated fragmentation of methyl 4,6-O-benzylidene-β-d-galactopyranoside results in the formation of methyl 4-O-benzoyl-6-bromo-6-deoxy-β-d-galactopyranoside and methyl 4-O-benzoyl-3-bromo-3-deoxy-β-d-gulopyranoside, as opposed to the methyl 6-O-benzoyl-3-bromo-3-deoxy-β-d-gulopyranoside originally reported. The kinetic methyl 4-O-benzoyl-6-bromo-6-deoxy-β-d-galactopyranoside rearranges to the thermodynamic methyl 4-O-benzoyl-3-bromo-3-deoxy-β-d-gulopyranoside under the reaction conditions, likely via a 3,6-anhydro galactopyranoside. The NBS-mediated cleavage of 4,6-O-benzylidene acetals in the galactopyranoside series is therefore shown to conform to the regiochemistry observed in the corresponding gluco- and mannopyranoside series with preferential cleavage of the C6–O6 bond by an ionic mechanism.