Deep Eutectic Solvent Compatible Metallic Catalysts: Cationic Pyridiniophosphine Ligands in Palladium Catalyzed Cross‐Coupling Reactions

Abstract

Nowadays, CÀCb ond formation is one of the reaction types that most interests organic chemists. Thus, it has become an essential tool in organic synthesis that provides access to compounds of great value for different areas;s uch as materials, pharmaceuticals or fine chemicals. This kind of reactions can be performed under catalytic conditions employing transitionmetals,a sf or Suzuki-Miyaura, [1] Heck, [2] Negishi, [3] Stille, [4] Kumada, [5] Hiyama, [6] and Sonogashira reactions. [7] All thesea pproaches are typicallyp erformedi nv olatile organic solvents (VOC), whichn owadays are would preferably be replaced by "greener"m edia. Am ediumc an be considered green when its components satisfy different criteria,s uch as non-toxicity,r ecyclability,l ow price, availability,b iodegradability,a nd renewability,a mong others. Some deep eutectic solvents (DESs) could be considered as an alternative to hazardousV OC solvents. DESs are systemsf ormed by simple mixing Lewis or Brønsted acids and bases. [8] As ar esult of the strongh ydrogen bond interactions, the melting or phase transition point becamem uch lower than that of each individual component. [9] Nevertheless, the use of DES as reactionm edia in organic synthesis is in its childhood, [10 ] with very few reports of related metal-catalyzed process. [11] Only,v ery recently,p alladiumc hemistry has startedt ob e tested in DESm edia. More specifically, Suzukir eaction has been performed using Pd(OAc) 2 (10 mol %) in at ernary mixture of mannitol, dimethyl urea and ammonium chloride as DES combination. [12] Regarding Sonogashira coupling, the synthesis of only two products have been published in DES medium (dmannose/DMU), whereas the Heck cross-couplingr eaction has been performed in d-mannose-dimethyl urea (DMU) as reaction media. [13] Other publishedp alladium-catalyzed reactions performed in DES media include Ts uji-Trost allylation of amines in methylated b-cyclodextrine-DMU, [14 ] synthesis of thiophenes in ChCl-glycerol, [15] as well as the Stille reaction in lactose-DMU-NH 4 Cl. [16] This latest example is especially interesting, because is one of the few examples in which al igand was added to theD ES media:t riphenylarsine, in combination with palladium, permitted the coupling of 4-bromoanisole and tetraphenylstannanei n8 7% yield. However,w hen the reaction was performed using CyJohnPhos (a Hartwig-Buchwald-type ligand), only am odest6 1% yield was obtained. These facts clearlyd emonstrate the importance of appropriate design of the ligand in order to get good results in this new media.With all these precedents, we aimed to develop DES compatible phosphine ligands, since the best traditional palladium ligandsf or cross-coupling reactions seemed not to be so effective in this kind of solvents. We thoughi nc ationic pyridiniophosphine structures [17] as general strategy for ligandsi nt he palladium-catalyzed cross-couplingr eactions.We started by the synthesis of ac ationic pyridiniophosphine ligand with ac hloride as counter ion (Scheme 1). In order ...

Solvent effects in palladium catalysed cross-coupling reactions

“…Transmission electron microscopy showed these to be well dispersed, suggesting that coordination by the solvent prevented aggregation. Although cationic phosphine ligands were advantageous for the cross coupling reactions studied by Marset et al, 356 Dilauro et al have recently shown that Suzuki couplings of aryl boronic acids or trifluoroborate salts with a wide range of aryl halides are possible in deep eutectic solvents without additional ligands added. 357 The success of these reactions appears to be strongly solvent dependent, with even structurally similar deep eutectic solvents giving different results.…”

A chemo-enzymatic tandem reaction in a mixture of deep eutectic solvent and water in continuous flow

“…Therefore, a well thought-out process and post-process treatment of DESs and it mixtures with water is required in order to get DES into industrial application. 20,21 Nevertheless, an impressive series of chemical 22,23 and enzymatic [24][25][26] reactions and also flow applications [27][28][29] were successfully conducted in DESs. We have recently shown the feasibility to combine the enzymatic decarboxylation of hydroxycinnamic acids catalyzed by phenolic acid decarboxylase from Bacillus subtilis (BsPAD) in water and Ru-catalyzed homo-coupling in organic solvents in a one-pot reaction for the synthesis of a series of bio-based stilbene derivatives.…”

Deep Eutectic Solvents as Reaction Media for the Palladium‐Catalysed C−S Bond Formation: Scope and Mechanistic Studies

“…The best result was obtained by using a mixture of choline chloride (ChCl) and acetamide with only 1 mol % of PdCl 2 . Since a phosphine ligand seems to be necessary for the reaction to proceed at good reaction rates, we decided to use recently reported phosphine ligand 1 (3 mol %, Table S1, Scheme ). Other possible safe sources of SO 2 were also tested (Table S2) as well as alternative aryl sources (Table S3), but none of them improved the result obtained with sodium metabisulfite and phenylboronic acid.…”