Dimethylisosorbide (DMI) as a Bio-Derived Solvent for Pd-Catalyzed Cross-Coupling Reactions

Abstract

Palladium-catalyzed bond-forming reactions, such as the ­Suzuki–Miyaura and Mizoroki–Heck reactions, are some of the most broadly utilized reactions within the chemical industry. These reactions frequently employ hazardous solvents; however, to adhere to increasing sustainability pressures and restrictions regarding the use of such solvents, alternatives are highly sought after. Here we demonstrate the utility of dimethyl isosorbide (DMI) as a bio-derived solvent in several benchmark Pd-catalyzed reactions: Suzuki–Miyaura (13 examples, 62–100% yield), Mizoroki–Heck (13 examples, 47–91% yield), and Sonogashira (12 examples, 65–98% yield).

Suzuki–Miyaura cross coupling is not an informative reaction to demonstrate the performance of new solvents

“…The desired coupling is of 4-bromotoluene to produce 4-phenyltoluene, assisted by the inclusion of the bis(diphenylphosphino)ferrocene ligand and 3 equivalents of base (Scheme 1a). In this work the proportion of water added is less than that previously optimised for reactions in Cyrene™ [3], and more than that previously optimised for reactions in DMI [6]. In case study 1, the majority of sol-vents resulted in conversion to the product in the range of 75-85% after 1 hour.…”

“…If there is an observable change in reaction performance correlating to one or more solvent properties (often polarity), then it is possible to identify and implement an optimum solvent. Suzuki-Miyaura cross coupling is the premier method of palladium catalysed carbon-carbon bond formation, making it an obvious case study to validate the performance of novel solvents [1][2][3][4][5][6][7]. The polarity of the solvent is known to determine the structure and activity of cata-lytic intermediates, the rate determining step, and stereochemistry (where applicable) of Suzuki-Miyaura cross couplings [8].…”

“…The solvent screening included twelve solvents. The following eminent green and bio-based solvents were included in the study to assess their ability to substitute conventional solvents: Cyrene™ [3], and its alcohol equivalent levoglucosanol [9], ethyl lactate [10], 2-methyltetrahydrofuran (2-MeTHF) [11], γ-valerolactone (GVL) [12], dimethyl isosorbide (DMI) [6], and propylene carbonate [7]. This study compares solvents under the same conditions to offer a fair comparison.…”

“…The first case study was adapted from that developed by Watson and co-workers [3,6]. The desired coupling is of 4-bromotoluene to produce 4-phenyltoluene, assisted by the inclusion of the bis(diphenylphosphino)ferrocene ligand and 3 equivalents of base (Scheme 1a).…”

Application of hindered ether solvents for palladium catalyzed Suzuki–Miyaura, Sonogashira and cascade Sonogashira cross-coupling reactions

“…2 Tetrahydrofuran (THF) is one of the most commonly used solvents for the Suzuki-Miyaura reaction, 3 but due to its potential for peroxide formation and the suspicion it is a carcinogen, is classified as hazardous or problematic by several solvent selection guides. 4,5 Several alternative ether solvents have been investigated for Suzuki-Miyaura reactions including cyclopentyl methyl ether (CPME), 3 2-methyltetrahydrofuran (2-MeTHF), 6 dimethyl isosorbide (DMI), 7 eucalyptol, 2 and oxymethylene dimethyl ether oligomers (OMEs). 8 The results are variable in eucalyptol 2 and Cyrene too.…”