Enantiospecific Solvolytic Functionalization of Bromochlorides

Herein,
we report that under mild solvolytic conditions, enantioenriched
bromochlorides can be ionized, stereospecifically cyclized to an array
of complex bromocyclic scaffolds, or intermolecularly trapped by exogenous
nucleophiles. Mechanistic investigations support an ionic mechanism
wherein the bromochloride serves as an enantioenriched bromonium surrogate.
Several natural product-relevant motifs are accessed in enantioenriched
form for the first time with high levels of stereocontrol, and this
technology is applied to the scalable synthesis of a polycyclic brominated
natural product. Arrays of nucleophiles including olefins, alkynes,
heterocycles, and epoxides are competent traps in the bromonium-induced
cyclizations, leading to the formation of enantioenriched mono-, bi-,
and tricyclic products. This strategy is further amenable to intermolecular
coupling between cinnamyl bromochlorides and a diverse set of commercially
available nucleophiles. Collectively, this work demonstrates that
enantioenriched bromonium chlorides are configurationally stable under
solvolytic conditions in the presence of a variety of functional groups.