Kumada–Grignard-type biaryl couplings on water

Abstract

Well-established, traditional Kumada cross-couplings involve preformed Grignard reagents in dry ethereal solvent that typically react, e.g., with aryl halides via Pd catalysis to afford products of net substitution. Therefore, in the work described, which appears to be counterintuitive, exposure of these same aromatic halides to catalytic amounts of Pd(II) and excess magnesium metal in pure water leads to symmetrical/unsymmetrical biaryls, indicative of a net Kumada-like biaryl coupling. Evidence is presented suggesting that Grignard reagents, formed in situ in water, may be involved.

Synthesis of Bi(hetero)aryls via Sequential Oxidation and Decarboxylation of Benzylamines in a Batch/Fully Automated Continuous Flow Process

“…In the first step, Ag I is oxidized to an Ag II species, and the continuity of the redox reactions led to the formation of phenylmethanimine (5), and again the combination of redox and hydrolysis reac-tion led to the formation of benzamide (10) and benzaldehyde (6). The formation of benzaldehyde, benzamide, and benzoic acid (7) was unequivocally detected during GC measurements, and can also be seen in the reaction time-profile in the earlier stages of the reaction (Figure 2). A control reaction again confirmed that benzaldehyde, benzamide and benzoic acid were formed during the reaction.…”

“…[16] Next, self-condensation of benzaldehyde and BzA gave N-benzylidene-1-phenylmethanamine (8). In the next step, the redox reaction led to the formation of N-benzylbenzamide (9, detected by GC analysis) and again consecutive redox processes generated benzoic acid (7). The ensuing redox reaction oxidizes the benzoic acid (7), leading to decarboxylation and aryl radical generation.…”

“…Transition metal‐catalyzed cross coupling reactions are widely used in organic synthesis, and have recently been incorporated into award‐winning green chemistry technology The reaction is one of the several cross‐coupling strategies (Minisci, Stille, Suzuki–Miyaura, Negishi, Hiyama–Denmark and Kumada) typically to form biaryls, which are common intermediates in drug synthesis . These innovative strategies have been able to create safer and eco‐friendly processes that avoid organic solvents, excess reagents and high temperatures, and follow a shorter route to directly convert C–H bonds to various valuable C–C and C–heteroatom bonds (e.g., C–halide, C–O, C–N, C–Si, and C–S) .…”

Murahashi Cross‐Coupling at −78 °C: A One‐Pot Procedure for Sequential C−C/C−C, C−C/C−N, and C−C/C−S Cross‐Coupling of Bromo‐Chloro‐Arenes

“…Very recently, Fe‐catalyzed Csp 2 –Csp 3 Kumada coupling of chlorobenzamides have been reported at 0 °C . An interesting article for the biaryl synthesis by homo‐ and hetero‐Kumada couplings in water has also been reported . Feringa and co‐workers have reported the use of Pd‐phosphine catalysts for the coupling of organolithium reagents and found that, despite high turnover frequencies, coupling below −10 °C was not feasible …”

Isolation and synthesis of pygmanilines, phenylurea derivatives from the Northeastern Atlantic lichen Lichina pygmaea

“…Using the molecular formula as evidence, a simple symmetric biaryl system was deduced as 2,2',4,4'-tetramethoxybiphenyl (3). Although this compound has been obtained by synthesis, 18 to the best of our knowledge, it is the first description of 3 as a natural product. A similar structure was proposed in a PhD thesis but NMR data were not fully consistent.…”