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. Issue 39 (24th June 2019)

• Record Type: Journal Article
• Authors: Sinha, Narayan; Heijnen, Dorus; Feringa, Ben L.; Organ, Michael G.
• Is Part Of: Chemistry. Volume 25:Issue 39(2019)
• Page Start: 9180
• Page End: 9184
• Publication Date: 2019-06-24
• Subjects: Murahashi coupling -- organolithium -- Pd catalysis -- PEPPSI -- sequential cross-coupling; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201901678
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: 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. Abstract : Pd catalysis at −78 °C : By combining a high‐reactivity organometallic reagent with a high‐reactivity catalyst, cross‐coupling by using Pd catalysis is now possible at −78 °C. The near diffusion‐limiting reactivity of Pd‐PEPPSI has allowed, for the first time, for the rapid injection of the organolithium reagent, given that the coupling outcompetes catalyst degradation by the nucleophile. Despite their high reactivity, these catalysts can deftly react Br in the presence of Cl electrophiles by using a temperature trigger.