453537-18-3

Upstream product

• 111-34-2 -butyl vinyl ether 
• 402-43-7 p-trifluoromethylphenyl bromide 
• 3622-76-2 (2-ethenyloxyethyl)dimethylamine 
• 455-13-0 4-Iodobenzotrifluoride 
• 98-56-6 4-chlorobenzotrifluoride 

Downstream Products

• 709-63-7 1-(4-trifluoromethylphenyl)ethanone 

Relevant academic research and scientific papers

Direct synthesis of protected arylacetaldehydes by palladium- tetraphosphine-catalyzed arylation of ethyleneglycol vinylether

Through the use of [PdCl(C3H5)]2/cis,cis, cis-1,2,3,4-tetrakis(diphenylphosphinomethyl) cyclopentane as a catalyst, a range of aryl bromides undergo Heck reaction with ethyleneglycol vinylether to give regioselectively protected arylacetaldehydes in good yields. The β-arylation products were obtained in the range 93-98% selectivity with electron-poor aryl bromides. Furthermore, this catalyst can be used at low loading, even for reactions of sterically hindered aryl bromides. The arylvinyl ethers intermediates undergo subsequent ketalization to give the corresponding 2-benzyl-1,3-dioxolane derivatives.

Hydrogen-bonding-promoted oxidative addition and regioselective arylation of olefins with aryl chlorides

The first, general, and highly efficient catalytic system that allows a wide range of activated and unactivated aryl chlorides to couple regioselectively with olefins has been developed. The Heck arylation reaction is likely to be controlled by the oxidative addition of ArCl to Pd(0). Hence, an electron-rich diphosphine, 4-MeO-dppp, was introduced to facilitate the catalysis. Solvent choice is critical, however; only sluggish arylation is observed in DMF or DMSO, whereas the reaction proceeds well in ethylene glycol at 0.1-1 mol % catalyst loadings, displaying excellent regioselectivity. Mechanistic evidence supports that the arylation is turnover-limited by the oxidative addition step and, most importantly, that the oxidative addition is accelerated by ethylene glycol, most likely via hydrogen bonding to the chloride at the transition state as shown by DFT calculations. Ethylene glycol thus plays a double role in the arylation, facilitating oxidative addition and promoting the subsequent dissociation of chloride from Pd(II) to give a cationic Pd(II)-olefin species, which is key to the regioselectivity observed.

Selective terminal heck arylation of vinyl ethers with aryl chlorides: A combined experimental-computational approach including synthesis of betaxolol

Reaction conditions have been developed for palladium-catalyzed terminal (β-) arylation of acyclic vinyl ethers with high regioselectivity using inexpensive aryl chlorides as starting materials and the P(t-Bu)3 releasing preligand [(t-Bu3)PH]BF4 as the key additive. This swift and straightforward protocol exploits non-inert conditions and controlled microwave heating to minimize handling and processing times and uses aqueous DMF or environmentally friendly PEG-200 as the reaction medium. The selectivity for linear β-product in PEG-200 is slightly higher than in aqueous DMF. DFT calculations support a ligand-driven selectivity rationale, where the electronic and steric influence of bulky P(t-Bu)3 ligand provides improved β-selectivity in the essential insertion step also with electron-rich aryl chlorides. A tentative computational rationalization of the improved selectivity in non-methylated PEG is discussed. Finally the synthetic methodology was used to provide efficient access to linear p-[2- (cyclopropylmethoxy)-ethyl] phenol from p-nitrophenyl chloride, a key intermediate in the synthesis of the β-adrenergic blocking agent Betaxolol.

Direct synthesis of protected arylacetaldehydes by tetrakis(phosphane)- palladium-catalyzed arylation of ethyleneglycol vinyl ether

A range of aryl bromides undergo Heck reaction with ethylene glycol vinyl ether, in the presence of [PdCl(C3H5)]2/ cis,cis,cis-1,2,3,4-tetrakis[(diphenylphosphanyl)methyl]cyclopentane as catalyst, to give regioselectively protected arylacetaldehydes in good yields. The β-arylation products were obtained in with 93-100 % selectivity with electron-poor aryl bromides or heteroaryl bromides. Furthermore, this catalyst can be used at low loading, even for reactions with sterically hindered aryl bromides. The aryl vinyl ether intermediates undergo subsequent ketalisation to give the corresponding 2-benzyl-1,3-dioxolane derivatives. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

A new efficient tetraphosphine/palladium catalyst for the Heck reaction of aryl halides with styrene or vinylether derivatives

cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C 3H5)]2 system efficiently catalyses the Heck reaction of aryl halides with styrene and vinylether derivatives. High turnover numbers can be obtained for the reaction of several aryl halides with styrene and styrene derivatives. Lower turnover numbers have been observed in the presence of vinylethers.

Aqueous DMF - Potassium carbonate as a substitute for thallium and silver additives in the palladium-catalyzed conversion of aryl bromides to acetyl arenes

Highly selective palladium-catalyzed internal α-arylations of alkyl vinyl ethers with aryl and heteroaryl bromides were conveniently conducted in aqueous DMF with potassium carbonate as base and with DPPP as bidentate ligand. The corresponding acetyl arene products were, after hydrolysis, isolated in good to excellent yields. This Heck reaction procedure does not require toxic thallium or expensive silver salt additives, is promoted by water, and is suggested to proceed via charged organopalladium intermediates. Single-mode microwave irradiation was utilized in one example to shorten the reaction time.