Potassium Trimethylsilanolate-Promoted, Anhydrous Suzuki–Miyaura Cross-Coupling Reaction Proceeds via the “Boronate Mechanism”: Evidence for the Alternative Fork in the Trail

Abstract

Previous studies have shown that the critical transmetalation step in the Suzuki–Miyaura cross-coupling proceeds through a mechanism wherein an arylpalladium hydroxide complex reacts with an aryl boronic acid, termed the oxo-palladium pathway. Moreover, these same studies have established that the reaction between an aryl boronate and an arylpalladium halide complex (the boronate pathway) is prohibitively slow. Herein, studies on isolated intermediates, along with kinetic analysis, have demonstrated that the Suzuki–Miyaura reaction promoted by potassium trimethylsilanolate (TMSOK) proceeds through the boronate pathway, in contrast with other, established systems. Furthermore, an unprecedented, binuclear palladium­(I) complex containing a μ-phenyl bridging ligand was characterized by NMR spectroscopy, mass spectrometry, and computational methods. Density functional theory (DFT) calculations suggest that the binuclear complex exhibits an open-shell ground electronic state, and reaction kinetics implicate the complex in the catalytic cycle. These results expand the breadth of potential mechanisms by which the Suzuki–Miyaura reaction can occur, and the novel binuclear palladium complex discovered has broad implications for palladium-mediated cross-coupling reactions of aryl halides.

Stereospecific Csp3 Suzuki–Miyaura Cross-Coupling That Evades β-Oxygen Elimination

“…This hypothesis is further supported by pinacol siloxaborolate 27-syn not requiring exogenous base for cross-coupling (Figure C). It is also consistent with studies from the Denmark lab illuminating the remarkable stability of Si–O–Pd­(II) pretransmetalation intermediates, and that Suzuki–Miyaura cross-couplings employing silanolate bases can proceed efficiently via a boronate transmetalation mechanism …”

Iron-Catalyzed C(sp2)-C(sp3) Suzuki Cross-Coupling Using an Alkoxide Base

“…Reaction optimization was conducted with N-Boc-4-bromopiperidine (2a) and the electron-deficient 3,5-trifluoromethylphenylboronic acid neopentylglycol ester (3b), previously shown by Denmark to undergo transmetalation to palladium through a boronate pathway. 20 With 10 mol% 1a in benzene solvent and a series of alkoxide bases, synthetically useful yields (>70%) of cross-coupled product were obtained (Table 1). KOEt proved optimal, providing 74% yield after 16 hours at 80 °C.…”

Suzuki C–C Coupling in Paper Spray Ionization: Microsynthesis of Biaryls and High-Sensitivity MS Detection of Aryl Bromides

“…As an organic base, TMSOK was also explored by Procopiou et al to prepare E -alkenes by inducing the elimination of potassium arenesulfinates from alkyl aryl sulfones. More importantly, the Denmark group found that TMSOK greatly promoted the Sonogashira reaction and the Suzuki–Miyaura reaction − under anhydrous conditions, reducing the reaction time by more than 10 times. The above examples show the considerable potential of TMSOK as a base to promote the homogeneous, anhydrous Suzuki–Miyaura cross-coupling. …”

“…), and hence suffered from the aforementioned criticisms. To the best of our knowledge, TMSOK-assisted Suzuki–Miyaura reactions have been rarely undertaken in thin film by PSI for microsynthesis of biphenyls, although TMSOK-assisted Suzuki–Miyaura reactions in bulk − and inorganic base-assisted Suzuki–Miyaura reactions by microdroplet chemistry (DESI-MS, , nanoESI-MS, PSI-MS, and sonic spray ionization) have been fully investigated.…”