A general method for the regioselective Heck reaction of electron-rich olefins is presented. Fast, highly regioselective Pd-catalysed alpha-arylation of electron-rich olefins, vinyl ethers (1 a-d), hydroxyl vinyl ethers (1 e, f), enamides (1 g, h) and a substituted vinyl ether (1i) has been accomplished with a diverse range of aryl bromides (2 a-r), for the first time, in cheap, green and easily available alcohols with no need for any halide scavengers or salt additives. The reaction proceeds with high efficiency, leading exclusively to the alpha-products, in 2-propanol and particularly in ethylene glycol. In the latter, the arylation can be catalysed at a palladium loading of 0.1 mol% and finish in as short a time as 0.5 h. The remarkable performance of the alcohol solvents in promoting alpha regiocontrol is attributed to their hydrogen-bond-donating capability, which is believed to facilitate the dissociation of halide anions from PdII, and hence, the generation of a key ionic PdII-olefin intermediate responsible for the alpha product. This belief is further strengthened by the study of a benchmark arylation reaction in 21 different solvents. The study revealed that exclusive alpha-regioselective arylation takes place in almost all of the protic solvents, and there is a rough correlation between the alpha-arylation rates and the solvent parameter E(T)N. The method is simpler, cleaner and more general than those established thus far.
meso-2,4-Bis(diphenylphosphino)pentane (mBDPP) has proved to be an effective regiocontrolling ligand for palladium-catalyzed internal arylation by aryl bromides of electron-rich olefins in a common solvent DMSO with no need for any halide scavengers. The arylation of the benchmark electron-rich olefin butyl vinyl ether took place smoothly to afford exclusively alpha-arylated product with high isolated yields. The better performance of mBDPP, compared with that of the commonly used DPPP [1,3-bis(diphenylphosphino)propane], highlights the important but subtle effect of ligand on the regioselectivity of the Heck arylation reactions.
The combination of Pd(OAc)(2) with 1,3-bis(diphenylphosphino)propane (dppp) in ethylene glycol constitutes a high-performance catalytic system for highly regioselective arylation of a range of electron-rich vinyl ethers by aryl bromides to provide, upon hydrolysis, alkyl aryl ketones and cyclic ketals in good yields with up to 3.75 x 10(5) TON and 15625 h(-1) TOF.
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