Introducing Deep Eutectic Solvents to Polar Organometallic Chemistry: Chemoselective Addition of Organolithium and Grignard Reagents to Ketones in Air

Abstract

Despite their enormous synthetic relevance, the use of polar organolithium and Grignard reagents is greatly limited by their requirements of low temperatures in order to control their reactivity as well as the need of dry organic solvents and inert atmosphere protocols to avoid their fast decomposition. Breaking new ground on the applications of these commodity organometallics in synthesis under more environmentally friendly conditions, this work introduces deep eutetic solvents (DESs) as a green alternative media to carry out chemoselective additions of ketones in air at room temperature. Comparing their reactivities in DES with those observed in pure water suggest that a kinetic activation of the alkylating reagents is taking place, favoring nucleophilic addition over the competitive hydrolysis, which can be rationalized through formation of halide-rich magnesiate or lithiate species.

Recent advances in the application of deep eutectic solvents as sustainable media as well as catalysts in organic reactions

“…39 (48) and α-substituted ketones (51)) can also be conveniently performed via Fischer indole synthesis in low melting L-(+)-tartaric acid (TA)/dimethyl urea (DMU) mixture (Scheme 18). However, this reaction is greatly limited by their requirements of low temperatures in order to control their reactivity as well as the need of dry organic solvents and inert atmosphere protocols to avoid their fast degradation of these polar reagents.…”

Organic Synthesis without Conventional Solvents

“…[142] Scheme 30. [155,156] Furthermore, palladium catalyzed C-C coupling reactions were performed in DES based on saccharides and DMU or urea, including the Stille, [157] Heck, Sonogashira, [158] and Suzuki [159] coupling. [142] As mentioned above, the Diels-Alder reaction was performed in Lewis-acidic ILs, namely [bpy][AlCl 4 ] and [emim][AlCl 4 ].…”

AuI Iminophosphorane Complexes as Efficient Catalysts for the Cycloisomerization of Alkynyl Amides under Air, at Room Temperature, and in Aqueous or Eutectic‐Mixture Solutions

“…[18] However, andd espite their great potentiala se nvironmentally friendly reaction media, there are currently very few examples in the literature of the use of these eutectic solvents, which are usually obtained by mixing aq uaternarya mmonium salt with ah ydrogen-bondd onor that can form ac omplex with Scheme1.Metal-catalyzed cycloisomerization of alkynyl amides requires the use of organics olvents and/or heating of the reaction medium. [19,20] With all these precedents in mind and taking into account 1) that as ustainable methodi ss till required for the preparation of alkylidene lactamst hrough the metal-catalyzed cycloisomerization of alkynyl amides, [5] 2) our previous studies on the catalytic activity of organometallic complexesc ontaining iminophosphorane ligands, [21] and 3) recent contributionst o the field of organic and organometallic synthesis in water and DESs, [22,23] we report herein an ew family of gold(I)c omplexes containing iminophosphorane-phosphine ligands, namely, [AuCl(k 1 -P-Ph 2 PCH 2 P{=NP(=S)(OR) 2 }Ph 2 )] (3 a,b)a nd [Au 2 Cl 2 (m 2 -P, S -Ph 2 PCH 2 P{=NP(=S)(OR) 2 }Ph 2 )] (4a,b), which are efficient catalysts for the regioselective cycloisomerizationo fa lkynyl amides in water or DESs. [19,20] With all these precedents in mind and taking into account 1) that as ustainable methodi ss till required for the preparation of alkylidene lactamst hrough the metal-catalyzed cycloisomerization of alkynyl amides, [5] 2) our previous studies on the catalytic activity of organometallic complexesc ontaining iminophosphorane ligands, [21] and 3) recent contributionst o the field of organic and organometallic synthesis in water and DESs, [22,23] we report herein an ew family of gold(I)c omplexes containing iminophosphorane-phosphine ligands, namely, [AuCl(k 1 -P-Ph 2 PCH 2 P{=NP(=S)(OR) 2 }Ph 2 )] (3 a,b)a nd [Au 2 Cl 2 (m 2 -P, S -Ph 2 PCH 2 P{=NP(=S)(OR) 2 }Ph 2 )] (4a,b), which are efficient catalysts for the regioselective cycloisomerizationo fa lkynyl amides in water or DESs.…”