Catalytic activation of unstrained C(aryl)-C(aryl) bonds in 2,2'-biphenols

Abstract

Transition metal catalysis has emerged as an important means for C-C activation that allows mild and selective transformations. However, the current scope of C-C bonds that can be activated is primarily restricted to either highly strained systems or more polarized C-C bonds. In contrast, the catalytic activation of non-polar and unstrained C-C moieties remains an unmet challenge. Here we report a general approach for the catalytic activation of the unstrained C(aryl)-C(aryl) bonds in 2,2'-biphenols. The key is to utilize the phenol moiety as a handle to install phosphinites as a recyclable directing group. Using hydrogen gas as the reductant, monophenols are obtained with a low catalyst loading and high functional group tolerance. This approach is also applied to the synthesis of 2,3,4-trisubstituted phenols. A further mechanistic study suggests that the C-C activation step is mediated by a rhodium(I) monohydride species. Finally, a preliminary study on breaking the inert biphenolic moieties in lignin models is illustrated.

Figure 1|. Catalytic activation of nonpolar unstrained C−C bonds.

a, Milstein’s seminal work on cleavage of the C(aryl)−C(alkyl) bond in a pincer ligand. b, Challenge for biaryl substrates: unlike activation of the C(aryl)−C(alkyl) bond, the twisted conformation of biaryls hinders the formation of the initial σ complex. c, Strategy of catalytic activation of unstrained C(aryl)−C(aryl) bonds of 2,2’-biphenols: the phenol moieties are used as the handle.

Figure 2|. Exploratory mechanistic study.

a, Two proposed mechanistic pathways for the C−C activation step. Path a starts with a Rh−Cl species and involves a formal Rh(V) intermediate; path b involves a Rh−H-mediated oxidative addition of the aryl−aryl bond. For computed activation energy, see Supplementary Section 14 for the DFT study. b, Stoichiometric Rh−Cl-mediated transformations in the absence of H₂ afforded a trace amount of product after heating, and the chlorine bridged dirhodium complex could be obtained at room temperature. c, A higher [Rh(C₂H₄)₂Cl]₂ loading led to significantly reduced yields and adding bases restored the yields. d, Stoichiometric reactions with Rh−H and Rh−Ph species. Stoichiometric Rh(PPh₃)₄H afforded product 3c in a moderate yield in the absence of H₂. PhLi could be used to transfer a phenyl group to the aryl−aryl bond. These results support path b

Figure 3|. Catalytic reductive cleavage of C(aryl)−C(aryl) bonds in 2,2’-biphenols.

a. Synthesis of 2,3,4-trisubstituted phenols. This method could be useful to prepare 2,3,4-trisubstituted phenols from substrate 5a. In contrast, the direct C−H activation approach only gives the 2,4,5-substituted product. For experimental details, see Supplementary Section 4. b. Scalability. The reaction can be run on a gram scale with a good yield. c. The reaction can be run in one pot directly from 2,2’-biphenols. d. The RDG moiety can be recycled. Simple treatment of the reaction mixture after C−C activation with dry HCl regenerates i-Pr₂PCl with a quantitative conversion. The lower isolated yield of i-Pr₂PCl is mainly caused by its volatility during the handling and purification.

Figure 4|. Model study for the cleavage of aryl−aryl bonds in lignin dimers.

a, Representative structure of softwood lignin, highlighting “5-5” and “dibenzodioxocin” units, which are arguably the most difficult linkers to be cleaved; in contrast, cleavage of the β-O-4 linkage has been widely studied. b, Conversion of “dibenzodioxocin” to “5-5” linkages. c, Conversion of wet spruce sawdust (2.5 g × 14 batches) to lignin monomers. For experimental details, see Supplementary Section 12.