70836-95-2Relevant academic research and scientific papers
Instantaneous SmI2/H2O/amine-mediated reductions in THF
Dahlen, Anders,Hilmersson, Goeran
, p. 1123 - 1128 (2003)
The SmI2-mediated reductions of ketones, imines, and α,β-unsaturated esters have been shown to be instantaneous in the presence of H2O and an amine in THF. The SmI2-mediated reductions are not only shown to be fast and quantitative by the addition of H2O and an amine, but the workup procedures are also simplified. Competing experiments with SmI2/H2O/amine confirmed that α,β-unsaturated esters could be selectively reduced in the presence of ketones or imines. Comparison of analogue ligands showed that nitrogen and phosphorus ligands are superior to oxygen and sulfur ligands in these reductions. The trialkylphosphine 1,2-bis(dimethylphosphino)ethane (DMPE) provided a primary kinetic isotope effect, yielding a kH/kD of 4.5.
Selective Construction of C?C and C=C Bonds by Manganese Catalyzed Coupling of Alcohols with Phosphorus Ylides
Liu, Xin,Werner, Thomas
, p. 1096 - 1104 (2020/12/31)
Herein, we report the manganese catalyzed coupling of alcohols with phosphorus ylides. The selectivity in the coupling of primary alcohols with phosphorus ylides to form carbon-carbon single (C?C) and carbon-carbon double (C=C) bonds can be controlled by the ligands. In the conversion of more challenging secondary alcohols with phosphorus ylides the selectivity towards the formation of C?C vs. C=C bonds can be controlled by the reaction conditions, namely the amount of base. The scope and limitations of the coupling reactions were thoroughly evaluated by the conversion of 21 alcohols and 15 ylides. Notably, compared to existing methods, which are based on precious metal complexes as catalysts, the present catalytic system is based on earth abundant manganese catalysts. The reaction can also be performed in a sequential one-pot reaction generating the phosphorus ylide in situ followed manganese catalyzed C?C and C=C bond formation. Mechanistic studies suggest that the C?C bond was generated via a borrowing hydrogen pathway and the C=C bond formation followed an acceptorless dehydrogenative coupling pathway. (Figure presented.).
Continuous flow multistep synthesis of α-functionalized esters via lithium enolate intermediates
von Keutz, Timo,Strauss, Franz J.,Cantillo, David,Kappe, C. Oliver
, p. 3113 - 3117 (2017/11/29)
This manuscript describes a continuous flow protocol for the α-alkylation of esters. The method is based on the generation of lithium enolate intermediates from the esters and in situ delivered LDA. The process is then integrated with the electrophilic addition step and a quench in line. A series of α-functionalized ester have been prepared using this procedure with moderate to good yields. Key reaction parameters such as temperature and residence time and their influence on the reaction outcome are discussed in detail.
A General and mild catalytic α-alkylation of unactivated esters using Alcohols
Guo, Le,Ma, Xiaochen,Fang, Huaquan,Jia, Xiangqing,Huang, Zheng
supporting information, p. 4023 - 4027 (2015/03/30)
Catalytic α-alkylation of esters with primary alcohols is a desirable process because it uses low-toxicity agents and generates water as the by-product. Reported herein is a NCP pincer/Ir catalyst which is highly efficient for α-alkylation of a broad scope of unactivated esters under mild reaction conditions. For the first time, alcohols alkylate unactivated α-substituted acyclic esters, lactones, and even methyl and ethyl acetates. This method can be applied to the synthesis of carboxylic acid derivatives with diverse structures and functional groups, some of which would be impossible to access by conventional enolate alkylations with alkyl halides. In a pinch: An NCP pincer/iridium catalyst is highly efficient for the α-alkylation of unactivated esters using alcohol under mild reaction conditions. The reaction is simple, clean, and scalable (1-10 mmol), and the scope with respect to the ester is wide.
Overturning established chemoselectivities: Selective reduction of arenes over malonates and cyanoacetates by photoactivated organic electron donors
Doni, Eswararao,Mondal, Bhaskar,O'Sullivan, Steven,Tuttle, Tell,Murphy, John A.
supporting information, p. 10934 - 10937 (2013/08/23)
The prevalence of metal-based reducing reagents, including metals, metal complexes, and metal salts, has produced an empirical order of reactivity that governs our approach to chemical synthesis. However, this reactivity may be influenced by stabilization of transition states, intermediates, and products through substrate-metal bonding. This article reports that in the absence of such stabilizing interactions, established chemoselectivities can be overthrown. Thus, photoactivation of the recently developed neutral organic superelectron donor 5 selectively reduces alkyl-substituted benzene rings in the presence of activated esters and nitriles, in direct contrast to metal-based reductions, opening a new perspective on reactivity. The altered outcomes arising from the organic electron donors are attributed to selective interactions between the neutral organic donors and the arene rings of the substrates.
On the mechanism of the palladium-catalyzed β-arylation of ester enolates
Larini, Paolo,Kefalidis, Christos E.,Jazzar, Rodolphe,Renaudat, Alice,Clot, Eric,Baudoin, Olivier
supporting information; experimental part, p. 1932 - 1944 (2012/03/22)
The palladium-catalyzed β-arylation of ester enolates with aryl bromides was studied both experimentally and computationally. First, the effect of the ligand on the selectivity of the α/β-arylation reactions of ortho- and meta-fluorobromobenzene was described. Selective β-arylation was observed for the reaction of o-fluorobromobenzene with a range of biarylphosphine ligands, whereas α-arylation was predominantly observed with m-fluorobromobenzene for all ligands except DavePhos, which gave an approximate 1:1 mixture of α-/β-arylated products. Next, the effect of the substitution pattern of the aryl bromide reactant was studied with DavePhos as the ligand. We showed that electronic factors played a major role in the α/β-arylation selectivity, with electron-withdrawing substituents favoring β-arylation. Kinetic and deuterium-labeling experiments suggested that the rate-limiting step of β-arylation with DavePhos as the ligand was the palladium-enolate-to-homoenolate isomerization, which occurs by a β-H-elimination, olefin-rotation, and olefin-insertion sequence. A dimeric oxidative-addition complex, which was shown to be catalytically competent, was isolated and structurally characterized. A common mechanism for α- and β-arylation was described by DFT calculations. With DavePhos as the ligand, the pathway leading to β-arylation was kinetically favored over the pathway leading to α-arylation, with the palladium-enolate-to-homoenolate isomerization being the rate-limiting step of the β-arylation pathway and the transition state for olefin insertion its highest point. The nature of the rate-limiting step changed with PCy3 and PtBu3 ligands, and with the latter, α-arylation became kinetically favored. The trend in selectivity observed experimentally with differently substituted aryl bromides agreed well with that observed from the calculations. The presence of electron-withdrawing groups on these bromides mainly affected the α-arylation pathway by disfavoring C-C reductive elimination. The higher activity of the ligands of the biaryldialkylphosphine ligands compared to their corresponding trialkylphosphines could be attributed to stabilizing interactions between the biaryl backbone of the ligands and the metal center, thereby preventing deactivation of the β-arylation pathway.
On the origins of diastereoselectivity in the alkylation of enolates derived from N-1-(1′-Naphthyl)ethyl-O-tert-butylhydroxamates: Chiral Weinreb amide equivalents
Davies, Stephen G.,Goodwin, Christopher J.,Hepworth, David,Roberts, Paul M.,Thomson, James E.
supporting information; experimental part, p. 1214 - 1227 (2010/04/26)
(Chemical Equation Presented) The stereochemical outcome observed upon alkylation of enolates derived from N-1-(1′-naphthyl)ethyl-O-tert- butylhydroxamates (chiral Weinreb amide equivalents) may be rationalized by a chiral relay mechanism. Deprotonation withKHMDS leads to a nonchelated (Z)-enolate inwhich the oxygen atoms adopt an anti-periplanar conformation. The configuration of the N-1-(1′-naphthyl)ethyl group dictates the conformation of the O-tert-butyl group and the configuration adopted by the adjacent pyramidal nitrogen atom. Highly diastereoselective enolate alkylation then proceeds anti to both the bulky tert-butyl group (sterically driven) and the N-lone pair (stereoelectronically driven).
Rhodium(I)-catalyzed 1,2- and 1,4-addition of aryltriethoxysilanes to carbonyl compounds under aqueous basic conditions
Murata, Miki,Shimazaki, Ryuta,Ishikura, Masanori,Watanabe, Shinji,Masuda, Yuzuru
, p. 717 - 719 (2007/10/03)
Aryltriethoxysilanes add to aldehydes and α,β-unsaturated carbonyl compounds in high yield in the presence of a rhodium(I) catalyst and aqueous sodium hydroxide.
2-Benzyl-2-methylsuccinic acid as inhibitor for carboxypeptidase A. synthesis and evaluation
Lee, Mijoon,Jin, Yonghao,Kim, Dong H.
, p. 1755 - 1760 (2007/10/03)
Recently, Asante-Appiah et al. (Asante-Appiah, E.; Seetharaman, J.; Sicheri, F.; Yang, D. S.-C.; Chan, W. W.-C. Biochemistry 1997, 36, 8710-8715) reported that 2-ethyl-2-methylsuccinic acid is a highly potent inhibitor for carboxypeptidase A (CPA), a prototypic zinc protease. The X-ray crystal structure of the complex of the enzyme formed with 2-ethyl-2-methylsuccinic acid revealed that at the active site of CPA there is present a small cavity which accommodates the methyl group of the inhibitor. These investigators postulated that incorporation of a methyl group at the α-position to the carboxylate of existing inhibitors of CPA would improve the inhibitory potency. We have synthesized racemic and optically active 2-benzyl-2-methylsuccinic acids and evaluated their inhibitory activities for CPA to find the K(i) values to be 0.28, 0.15, and 17μM for racemic form, (R)-, and (S)-enantiomer, respectively. Contrary to the expectation, the effect on the binding affinity by the incorporation of the methyl group is minimal. The validity of the proposition that the small cavity may be utilized for the improvement of the inhibitory potency appears questionable. Copyright (C) 1999 Elsevier Science Ltd.
