Water and Sodium Chloride: Essential Ingredients for Robust and Fast Pd‐Catalysed Cross‐Coupling Reactions between Organolithium Reagents and (Hetero)aryl Halides

Abstract

Direct palladium-catalysed cross-couplings between organolithiums and (hetero)aryl halides (Br, Cl) proceed fast, cleanly and selectively at room temperature in air, with water as the only reaction medium and in the presence of NaCl as a cheap additive. Under optimised reaction conditions, a water-accelerated catalysis is responsible for furnishing Csp 3 -Csp 2 , Csp 2 -Csp 2 , and Csp-Csp 2 cross-coupled products, competitively with protonolysis, within a 20 s reaction time, in yields of up to 99%, and in the absence of undesired dehalogenated/homocoupling side-products even if it starts from challenging secondary organolithiums. It is worth noting that the proposed protocol is scalable and the catalyst and water can easily and successfully be recycled up to 10 times, with an E-factor as low as 7.35.

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

“…Gradual charging of the reagent mitigates fast organolithium‐related catalyst decomposition. What would be required to make the more‐desirable, single‐shot injection of the nucleophile possible is for catalysis to be so rapid that decomposition (presuming that it occurs) cannot complete with the desired pathway . Key would be a catalyst system capable of undergoing OA at near diffusion‐limiting rates.…”

Solvent effects in palladium catalysed cross-coupling reactions

“…Surprisingly, it has been recently reported that the direct coupling of n-BuLi and 1-bromonaphthalene, using Pd(P t Bu 3 ) 2 as the catalyst, is possible in choline chloride-based deep eutectic solvents, even in the presence of protic functionality and water in the solvent. 358 While significant amounts of naphthalene, the product of a competing dehalogenation reaction, were formed in all the deep eutectic solvents studied, this reaction could be optimised to take place in (or more appropriately on) water containing sodium chloride. This is an exciting finding and offers significant potential for organometallic catalysis in sustainable solvent systems.…”

Sustainable Ligand‐Free Heterogeneous Palladium‐Catalyzed Sonogashira Cross‐Coupling Reaction in Deep Eutectic Solvents

“…A notable exception is represented by the employment of γ‐valerolactone as an alternative, non‐toxic biomass‐derived medium solvent for synthesizing acetylene‐containing systems starting from (hetero)aryl iodides . Based on our ongoing interest in using water and DESs to explore novel paradigms in metal‐mediated and metal‐catalyzed organic transformations, herein we report the results of a study demonstrating the usefulness of a recycling biocompatible DES such as ChCl/Gly as an environmentally responsible reaction medium for carrying out ligand‐free SH couplings between (hetero)aryl iodides and terminal aryl‐ or alkyl‐substituted alkynes with a broad substrate scope, and working under heterogeneous conditions by using a cheap and recyclable catalyst such as Pd/C (Scheme d).…”