74031-79-1Relevant articles and documents
Electronic Effect-Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols
Li, Dan-Yang,Lou, Yu-Jiao,Xu, Jian,Chen, Xiao-Yang,Lin, Xian-Fu,Wu, Qi
, p. 1867 - 1872 (2021/02/12)
Herein, we developed an electronic effect-guided rational design strategy to enhance the enantioselectivity of Candida antarctica lipase B (CALB) mutants towards bulky pyridyl(phenyl)methanols. Compared to W104A mutant previously reported with reversed S-stereoselectivity toward sec-alcohols, three mutants (W104C, W104S and W104T) displayed significant improvement of S-enantioselectivity in the kinetic resolution (KR) of various phenyl pyridyl methyl acetates due to the increased electronic effects between pyridyl and polar residues. The electronic effects were also observed when mutating other residues surrounding the stereospecificity pocket of CALB, such as T42A, S47A, A281S or A281C, and can be used to manipulate the stereoselectivity. A series of bulky pyridyl(phenyl) methanols, including S-(4-chlorophenyl)(pyridin-2-yl) methanol (S-CPMA), the intermediate of bepotastine, were obtained in good yields and ee values. (Figure presented.).
Metal-Free Halogen(I) Catalysts for the Oxidation of Aryl(heteroaryl)methanes to Ketones or Esters: Selectivity Control by Halogen Bonding
Guha, Somraj,Sekar, Govindasamy
, p. 14171 - 14182 (2018/09/10)
Metal-free halogen(I) catalysts were used for the selective oxidation of aryl(heteroaryl)methanes [C(sp3)?H] to ketones [C(sp2)=O] or esters [C(sp3)?O]. The synthesis of ketones was performed with a catalytic amount of NBS in DMSO solvent. Experimental studies and density functional theory (DFT) calculations supported the formation of halogen bonding (XB) between the heteroarene and N-bromosuccinimide, which enabled imine–enamine tautomerism of the substrates. No additional activator was required for this crucial step. Isotope-labeling and other supporting experiments suggested that a Kornblum-type oxidation with DMSO and aerobic oxygenation with molecular oxygen took place simultaneously. A background XB-assisted electron transfer between the heteroarenes and halogen(I) catalysts was responsible for the formation of heterobenzylic radicals and, thus, the aerobic oxygenation. For selective acyloxylation (ester formation), a catalytic amount of iodine was employed with tert-butyl hydroperoxide in aliphatic carboxylic acid solvent. Several control reactions, spectroscopic studies, and Time-Dependent Density Functional Theory (TD–DFT) calculations established the presence of acetyl hypoiodite as an active halogen(I) species in the acetoxylation process. With the help of a selectivity study, for the first time we report that the strength of the XB interaction and the frontier orbital mixing between the substrates and acyl hypoiodites determined the extent of the background electron-transfer process and, thus, the selectivity of the reaction.
(2-Pyridyl)phenyl methanol: A new reagent for metal-free reduction of nitro aromatic compounds
Giomi, Donatella,Alfini, Renzo,Brandi, Alberto
experimental part, p. 167 - 172 (2011/02/27)
As previously reported for 1-(2-pyridyl)-2-propen-1-ol, (2-pyridyl)phenyl methanol is able to react as hydrogen donor towards nitro aromatic and heteroaromatic compounds. Operating in the presence of methyl acrylate as an aza-Michael acceptor, a domino process involving reduction and conjugate addition steps allows the one pot formation of β-amino esters. The crucial role of the pyridine nucleus in making this purely thermal reactivity of carbinols possible has been shown.
