Real-Time Mass Spectrometric Investigations into the Mechanism of the Suzuki–Miyaura Reaction

Abstract

Real-time monitoring of the Suzuki–Miyaura reaction using mass spectrometry during sequential addition of the various reaction components suggests that a dynamic series of equilibria exist in these solutions. Depending on conditions, the boronic acid can be dehydrated, deprotonated, hydroxylated (or alkoxylated), or fluorinated. Palladium–phosphine species present include Pd(0) (to which the aryl iodide rapidly oxidatively adds), the Pd­(II) aryl iodide complex, a cationic Pd­(II) species formed by dissociation of the iodide ligand, and the Pd­(II) bisaryl complex that ultimately extrudes the product through reductive elimination. No fluorinated or hydr­(alk-)­oxylated palladium complexes were observed under catalytic conditions. Several transmetalation combinations were excluded as reactive partners, but several possibilities remain, and more than one mechanism is likely to be operative, even under similar conditions.

Identifying reactive intermediates by mass spectrometry

“…Many of such studies originate from the group of McIndoe. 63,64 We will present here an example of their study of Suzuki-Miyaura reaction. Without going into details of the reaction mechanism, we will concentrate of real time monitoring of the reaction progress with ESI-MS. 63 The palladium-catalysed cross-coupling reactions operate in the catalytic cycles between palladium(0) complexes and palladium(II) complexes bearing two anionic ligands.…”

“…65 The permanently charged group can be attached to a phosphine ligand coordinated to palladium (e.g., one of the phenyl groups in Ph 3 P ligand can be sulfonated) 66 or to a reactant. 63 The advantage of charge tagging is that the process of the ion transfer during electrospray is quasi-identical for all the charge tagged ions and thus it allows their simultaneous monitoring and even evaluation of the signal intensity changes during the monitoring.…”

“…12). 63 They have shown that using charge-tagging of the reactant can allow quantitative monitoring of reaction kinetics. Under the standard coupling conditions, they showed that ESI-MS data can reproduce rst-order kinetics of this reaction (see the insert in Fig.…”

Recent Advances in Metal-Catalyzed Alkyl–Boron (C(sp3)–C(sp2)) Suzuki-Miyaura Cross-Couplings

“…Ambiguity occurs since inorganic bases in aqueous or alcohol solvents, generating the required alkoxy or hydroxy ligands, are commonly employed in the SMC, to accelerate either pathway A or B. However, all DFT (Density Functional Theory) studies and ES-MS (Electrospray Ionization-Mass Spectrometry) investigations [63,64], where boronate species were observed and not oxo-palladium ones [65][66][67], support pathway A. Studies defending the suggestion of pathway B consist of kinetic analysis and experimental observations of the lack of activities in some cases in the presence of organic Lewis bases or lithium salts of boronic species.…”

Disulfonated xantphos for mass spectrometric mechanistic analysis

“…25,[30][31][32][33][34][35] We were particularly interested in the report [7a] that a co-catalytic system for direct arylation of heteroarenes involved a xantphos complex of copper that did not exchange ligands with the palladium present (Scheme 1 and 2). Given that xantphos typically enthusiastically binds Pd, [36][37][38] we planned to probe the copper/palladium/xantphos interaction in more detail using real-time ESI-MS, 39,40 as a way to assess its efficacy as a reaction probe and to point the way to further mechanistic studies.…”