Murahashi Cross-Coupling at -78 °C: A One-Pot Procedure for Sequential C-C/C-C, C-C/C-N, and C-C/C-S Cross-Coupling of Bromo-Chloro-Arenes.

The coupling of organolithium reagents, including strongly hindered examples, at cryogenic temperatures (as low as -78 °C) has been achieved with high-reactivity Pd-NHC catalysts. A temperature-dependent chemoselectivity trigger has been developed for the selective coupling of aryl bromides in the presence of chlorides. Building on this, a one-pot, sequential coupling strategy is presented for the rapid construction of advanced building blocks. Importantly, one-shot addition of alkyllithium compounds to Pd cross-coupling reactions has been achieved, eliminating the need for slow addition by syringe pump.