Mechanistic Insight from Lewis-Acid-Dependent Selectivity and Reversible Haloboration, as Harnessed for Boron-Based Electrophilic Cyclization Reactions

Different reaction selectivity occurs with the Lewis
acids B-chlorocatecholborane (ClBcat), B-bromocatecholborane
(BrBcat), and BBr3, favoring either alkyne haloboration,
electrophilic cyclization of a tethered nucleophilic sulfur onto the
alkyne, or group transfer of the nucleophile. This reaction selectivity
also depends on the chain length of the tethered nucleophile, revealing
a subtle interplay of relative kinetics and thermodynamics. In all
cases, BBr3 reacts readily with alkynes to form haloborated
products; however, this process is reversible, and this reversibility
can be harnessed to ultimately access regio- and stereodefined cyclic
sulfonium zwitterions via the slower but thermodynamically favored
electrophilic cyclization pathway. Reversibility was noted by following
the reaction by NMR spectroscopy, and by characterizing the kinetic
and thermodynamic products by a combination of 2D NMR spectroscopy
and single-crystal X-ray diffraction. The “mixed” reagent
bromocatechol borane (BrBcat) displayed reactivity between ClBcat
and BBr3, producing bromoboration in some cases and electrophilic
cyclization in others. With this enhanced understanding of the reaction
dynamics, it becomes possible to use boron Lewis acids in a predictable
manner in cases where haloboration is the kinetic product but in which
the reversibility of this reaction maintains access to eventual alternative
reactivity leading to desired building blocks in organic synthesis.