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 organolithium reagents 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 C(sp3)–C(sp2), C(sp2)–C(sp2), and C(sp)–C(sp2) cross‐coupled products, in competition with protonolysis, within a reaction time of 20 s, in yields of up to 99 %, and in the absence of undesired dehalogenated/homocoupling side products even when challenging secondary organolithiums serve as the starting material. 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.

Water as a solvent: transition metal catalyzed dehydrogenation of alcohols going green

“…53,154 Additionally, in the last few years, the instability issues of the reactive reagents in an aqueous medium were effectively addressed which invalidates the traditional mindset of the synthetic chemist. 37,39,42 One of the major advantages in developing transition-metal catalyzed organic transformations in an aqueous medium is the relatively easier separation of the products and the catalysts. Due to the highly polar and protic nature of water, most of the common organic compounds are insoluble/sparingly soluble in water which facilitates the separation of the products by simple phase separation or extraction.…”

“…37,38 The recent development of water-soluble catalysts assists in promoting several catalytic reactions in water such as cross coupling reactions, C–H activation, hydroformylation reactions, oxidation/reduction, rearrangement reactions, etc . 39–45 Detailed mechanistic studies were carried out to understand these processes in the aqueous phase and based on the solubilities of the substrate/catalyst, reactions using water as a solvent were classified as “in water”, “on water” or micellar catalysis. 46–49 For example, the process will be called “on water” if there is no solvation of the reaction components and an “in water” reaction is one where the presence of any additives assists the solubilization of the otherwise insoluble substrates/catalysts, etc .…”

New Frontiers in Organosodium Chemistry as Sustainable Alternatives to Organolithium Reagents

“…Thus, using hexane as a solvent, a range of highly reactive C(sp 3 ), C(sp 2 ) and C(sp) bonded organosodiums have been prepared in situ which subsequently undergo electrophilic interception in DES or even in water as the reaction medium (Figure 5). [24] It was initially demonstrated that sodiated anisole could be formed in hexane from the reaction of elemental sodium and 2-chloroanisole. Under their optimal conditions of using 4 equivalents of metallic sodium to form 1.8 equivalents of the sodiated anisole, the formed aryl sodium complex could be quenched with benzaldehyde under vigorous stirring in a DES mixture of 1 : 3 L-proline/glycerol (Pro/Gly) in a 94 % yield.…”

“…Thus, using hexane as a solvent, a range of highly reactive C(sp 3 ), C(sp 2 ) and C(sp) bonded organosodiums have been prepared in situ which subsequently undergo electrophilic interception in DES or even in water as the reaction medium (Figure 5). [24] …”

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. [46] Based on our ongoing interest in using water and DESs to explore novel paradigms in metal-mediated and metalcatalyzed organic transformations, [47][48][49][50][51][52][53][54][55][56][57] 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 1d).…”