Metal-mediated reactions of bromoform with electron-rich and electron-deficient carbon-carbon and carbon-hetero atom multiple bonds

Abstract

The addition of bromoform to carbon-carbon and carbon-heteroatom multiple bonds has gathered interest from the synthetic community as it leads to brominated molecules that find applications in agrochemicals, pharmaceuticals, polymers, and radiolabeled agents. The chemistry of di- and tri-brominated functionalized olefins remains scarcely explored. It may be due to their high steric demand and their propensity to form halogen bonds. The addition of bromoform to olefins in the presence of protic bases and a phase-transfer catalyst is well-established. However, their metal-mediated versions leading to new brominated compounds did not receive much attention. The addition of bromoform mediated by metals provides an opportunity to construct various synthetic intermediates and understand the underlying mechanistic aspects. Herein, we present the approaches reported in the last two decades on the bromocyclopropanation, atom transfer radical additions, hydroalkylations, and conjugate additions of bromoform to electron-rich and electron-deficient olefins under metal-mediated conditions. These approaches are expected to set the stage for hitherto unexplored asymmetric transformations and synthesis of complex molecules, including natural products, involving metal-mediated bromoform addition as the key step.

Graphical abstract

Reactions of bromoform with various multiple bonds such as olefins, carbonyl compounds, and imines under metal-mediated conditions are reviewed here. The methodology includes tribromomethylation, dibromomethylenation, dibromocyclopropanation, etc., and is a superior alternative to conventional base-mediated conditions.