ABSTRACT
Regiodivergent reactions are a fascinating tool to rapidly access molecular diversity while using identical coupling partners. We have developed a new approach for regiodivergent synthesis using the dual character of hypervalent bromines. In addition to the recently reported reactivity of hypervalent bromines as aryne precursors, the first transition metal-catalyzed reaction is reported. Accordingly, the development of these two complementary transformations allows for the alteration of regioselectivity to furnish both ortho- and meta-substituted alkynylation products. Mechanistic and computational studies show how these selectivities are controlled.
ABSTRACT
Hypervalent bromine(III) reagents possess a higher electrophilicity and a stronger oxidizing power compared to their iodine(III) counterparts. Despite the superior reactivity, bromine(III) reagents have a reputation of hard-to-control and difficult-to-synthesize compounds. This is partly due to their low stability, and partly because their synthesis typically relies on the use of the toxic and highly reactive BrF3 as a precursor. Recently, we proposed chelation-stabilized hypervalent bromine(III) compounds as a possible solution to both problems. First, they can be conveniently prepared by electro-oxidation of the corresponding bromoarenes. Second, the chelation endows bromine(III) species with increased stability while retaining sufficient reactivity, comparable to that of iodine(III) counterparts. Finally, their intrinsic reactivity can be unlocked in the presence of acids. Herein, an in-depth mechanistic study of both the electrochemical generation and the reactivity of the bromine(III) compounds is disclosed, with implications for known applications and future developments in the field.