Ruthenium(0)-Catalyzed Cross-Coupling Of Aryl Methyl Ethers By Selective C-O Arylation

In contrast to the cross-coupling technologies using aryl halides,the development of methods for C-O bond activation has been recognized as a powerful tool due to the orthogonal nature of C-O bonds,greater availability of common phenols than aryl halides,and a more sustainable profile due to the avoidance of toxic halide by-products.However,this process is highly challenging due to the high dissociation energy.The existing activation of C-O bond mostly requires expensive catalysts,which have high reaction costs and low functional group tolerance.Herein,we report a mild Ru(0)-catalyzed cleavage of C(aryl)-O bonds enabled by a combination of a Ru3(CO)12 catalyst and imine auxiliary.This method offers rapid entry to synthetically valuable biaryl aldehydes from abundant anisoles.This not only broadens the range of use of transition metal ruthenium,but also provides a new strategy for selective activation of inert C-O bond.This article first reviews the current research status of C-O bond activation catalyzed by metals such as nickel,palladium,cobalt,iron,chromium,and ruthenium.Subsequently,a mild Ru(0)-catalyzed cleavage of C(aryl)-O bonds enabled by a combination of a Ru3(CO)12 catalyst and an imine auxiliary was investigated.The research content of this article mainly includes:firstly,the N-imine of 2,6-dimethoxybenzaldehyde and neopentylphenylborate ester were used as a model system for condition optimization,and the optimal conditions including catalyst type,imine substituent type,arylborate ester type,solvent,temperature,time,and reactant feed ratio were optimized.With the optimized conditions in hand,the scope of this C-OMe activation was next investigated.This cross-coupling is uniformly compatible with electronically-diverse nucleophiles,including electron-deficient,electron-rich nucleophiles,as well as substrates with fused and heterocyclic rings.Finally,18 complex biarylaldehyde compounds were synthesized in 52%to 85%yield.Subsequently,a series of derivative experiments were conducted,including:(a)the Ru(0)-catalyzed C-OMe activation proceeds in the presence of carbon halide bonds;(b)the feasibility of C-H vs.C-OMe activation under Ru(0)catalysis;(c)the feasibility of C-OMe vs.C-F activation under Ru(0)catalysis;(d)Ir-catalyzed CHO defunctionalization.Finally,we conducted DFT(density functional theory)studies to gain insight into the C-OMe selectivity of this process.