In-Situ Bromination Enables Formal Cross-Electrophile Coupling of Alcohols with Aryl and Alkenyl Halides

Abstract

Although alcohols are one of the largest pools of alkyl substrates, approaches to utilize them in cross-coupling and cross-electrophile coupling are limited. We report the use of 1° and 2° alcohols in cross-electrophile coupling with aryl and vinyl halides to form C(sp3)–C(sp2) bonds in a one-pot strategy utilizing a very fast (<1 min) bromination. The reaction’s simple benchtop setup and broad scope (42 examples, 56% ± 15% average yield) facilitates use at all scales. The potential in parallel synthesis applications was demonstrated by successfully coupling all combinations of 8 alcohols with 12 aryl cores in a 96-well plate.

Topics & Concepts