Mechanistic Insight into Rh-Catalyzed C(sp²)–O Bond Cleavage Applied to Cross-Coupling Reaction of Benzofurans with Aryl Grignard Reagents

Abstract

A mechanistic study of the Rh-catalyzed cross-coupling reaction of vinylic ethers with aryl Grignard reagents via C­(sp2)–O bond cleavage is reported herein. To obtain mechanistic insights, the reaction was conducted in a flow reactor, and kinetic studies revealed that the reaction obeyed first-order and zeroth-order kinetics, with respect to vinyl ether and aryl Grignard reagents, respectively. The olefinic ligands in the Rh precatalysts significantly affected the catalytic performance, and the catalytic activity of [RhCl­(CH2CH2)2]2 was ca. 110 times higher than that of [RhCl­(cod)]2. Furthermore, the kinetic studies revealed that bidentate ancillary ligand, COD, forms a dormant species to decelerate the catalytic turnover. Computational studies suggested that the reaction between diarylrhodate, generated by the reaction of a Rh precatalyst with two molecules of aryl Grignard reagents, and vinylic ethers proceeded through Mg cation-assisted insertion/anti-β-oxygen elimination rather than oxidative addition/reductive elimination and nucleophilic substitution at the vinylic carbon (SN2 V). In the transition state, the Mg countercation was coordinated to the ethereal oxygen atom in the substrate and facilitated not only C–O bond cleavage but also the insertion of the CC bond into the Rh–Ph bond. These strategies and mechanistic insights were successfully applied to develop a strategy for the Rh-catalyzed cross-coupling reaction of fused vinylic ethers, benzofurans, and aryl Grignard reagents, wherein the bond cleavage occurred selectively at the vinylic C­(sp2)–O bond, even in the presence of Ar–O, Ar–Cl, or Ar–Br bonds. These results demonstrated the unique chemoselectivity of the present Rh-catalyzed reaction, which will allow the development of a complementary synthetic approach to the existing Ni-catalyzed cross-coupling reaction via C–O bond cleavage.

Rh-catalyzed ring-opening coupling of cyclic vinyl ethers with organometallic reagents

“…While no reaction was observed with the use of a phenyl zinc reagent (entry 3), Grignard reagents worked well to give the coupling product in high yields (entries 4 and 5). 17 Control experiments proved that the unique reactivity of a Grignard reagent did not arise simply from its basicity, the presence of Mg( ii ) or the background reaction (entries 6–9). The reaction proceeded in other anhydrous aprotic solvents, but the yield was lower (entries 10 and 11).…”

“…The thermally stable E -product was selectively obtained due to the facile isomerization of hydroxylated stilbenes. 10 b ,17…”

“…In the case of benzofuran, intermediate A is first formed via transmetalation, but the reaction does not proceed except when using a Grignard reagent. Inspired by Kambe's study, 9 an anionic organorhodium intermediate D is proposed, which reacts with benzofuran via Mg( ii )-facilitated insertion 17 followed by subsequent antiperiplanar β-oxygen elimination to give the Z -selective ring-opening intermediate. Finally, the hydroxylated stilbene readily isomerizes to the thermally stable E -product.…”

Cp* non-innocence and the implications of (η4-Cp*H)Rh intermediates in the hydrogenation of CO2, NAD+, amino-borane, and the Cp* framework – a computational study

“…The calculated free energy profile for Cp* hydrogenation in water starting from 4 follows a similar trend (see Scheme S1 in the ESI †). In either case, the dissociation of bis-olefinic η 2 -Cp*H 3 from 13′ (or 13, see the ESI †) can be expected to be more facile 58 than that of the mono-olefinic η 4 -Cp*H from 11′ (or 11, see the ESI †), which is consistent with the observation of 1,2,3,4,5-pentamethylcyclopent-1-ene as the major product of decomposition. 10 Although certainly not the only possibility, such hydrogenation of the Cp* framework might lead to catalyst degradation.…”