Ligand‐Free Pd‐Catalyzed Reductive Mizoroki‐Heck Reaction Strategy for the One‐Pot Synthesis of Functionalized Oxygen Heterocycles in Deep Eutectic Solvents

Abstract

Dedicated to Professor Francesco Naso on the occasion of his 85th birthdayA Deep Eutectic Solvent, choline chloride/glycerol (1 : 2 mol mol À 1 ), proved to be an effective and sustainable reaction medium to promote telescoped, one-pot Mizoroki-Heck cross-coupling/reduction processes between 2,3-dihydrofuran or 3,4-dihydro-2H-pyran and several (hetero)aryl halides to easily access valuable 2-(hetero)aryl tetrahydrofuran (THF) or tetrahydropyran derivatives in up to 95 % yield. Notably, the whole transformation takes place under aerobic conditions, in the absence of additional ligands, and with a good substrate scope. The practicability of the method is also exemplified by the sustainable synthesis of two key THF derivatives, which are side chains of pharmacologically relevant inhibitors of Kv1.2 channel.

Application of Deep Eutectic Solvents in Formation of Carbon‐Carbon and Carbon‐Heteroatom Bond by Cross‐Coupling Reactions

“…After the ligand-free Suzuki-Miyaura reaction developed by Giuseppe in 2018, the ligand-free Heck-Mizoroki reaction involving DESs was investigated in detail. [32] The one-pot Heck-Mizoroki cross-coupling/reduction reaction of aryl (hetero) halides with 2,3-dihydrofuran or 3,4-dihydropyran in DESs could afforded 2-aryl (hetero)-substituted saturated oxycycles in high yields with a fair substrate range (Figure 6). The experimental [a] Reaction carried out employing [1,1'-biphenyl]-2-yldicyclohexylphosphine as a ligand.…”

Top-ranked efficiency under indoor light of DSSCs enabled by iodide-based DES-like solvent electrolyte

“…At the beginning of the century, novel environmentally responsible fluids known as deep eutectic solvents (DESs) were recognized as promising alternatives to traditional VOCs in several fields of science, such as organic synthesis, 25,26 catalysis, 27–29 main group chemistry, 30–32 materials chemistry, 33,34 extraction and separation, 35–37 crystallography, 38 and also solar technology to stabilize and improve the photovoltaic performance of DSSCs, 39–47 due to their low volatility, high thermal stability, nonflammability, ease of preparation, low cost, and tunability of their physicochemical properties. Despite these advantages, however, there are still concerns about their toxicity.…”

Pd-Catalyzed Miyaura Borylation and Telescopic Borylation/Suzuki–Miyaura Cross-Coupling Processes in Deep-Eutectic Solvents

“…50 Surprisingly, DESs were also revealed to be suitable media for the addition of highly polar organometallic reagents, like organo-lithium, 51 magnesium, 52 and even sodium, 53 to electrophiles, allowing very high conversions at room temperature and under air, with very short reaction times. Furthermore, the great potential of DESs has been fully expressed through their successful application as reaction media in several crosscoupling reactions, 54−56 like Suzuki−Miyaura, 57,58 Sonogashira, 59 Hiyama, 60 Negishi, 61 Stille−Migita, 62 C−H direct arylation, 63,64 Mizoroki-Heck, 65,66 Chan-Evans-Lam 67 our knowledge, DESs have never been employed as reaction media in a Miyaura borylation reaction, and a one-pot borylation-Suzuki−Miyaura protocol in DES has never been reported. Considering these premises, taking advantage of our previous experience in the optimization of reaction protocols in DESs 63 and our long-standing expertise in the synthesis of organic conjugated molecules for photovoltaic applications through cross-coupling reactions, 71−75 we were interested in developing an efficient and robust Miyaura borylation protocol in DESs, and possibly combine it with a Suzuki−Miyaura coupling.…”

“…Surprisingly, DESs were also revealed to be suitable media for the addition of highly polar organometallic reagents, like organo-lithium, magnesium, and even sodium, to electrophiles, allowing very high conversions at room temperature and under air, with very short reaction times. Furthermore, the great potential of DESs has been fully expressed through their successful application as reaction media in several cross-coupling reactions, − like Suzuki–Miyaura, , Sonogashira, Hiyama, Negishi, Stille–Migita, C–H direct arylation, , Mizoroki-Heck, , Chan-Evans-Lam and C–N, C–O, and C–S couplings. Despite that, to the best of our knowledge, DESs have never been employed as reaction media in a Miyaura borylation reaction, and a one-pot borylation-Suzuki–Miyaura protocol in DES has never been reported.…”