59733-95-8Relevant academic research and scientific papers
Enantioselective Synthesis of α-Trifluoromethyl Amines via Biocatalytic N-H Bond Insertion with Acceptor-Acceptor Carbene Donors
Adukure, Ronald D.,Fasan, Rudi,Khare, Sagar D.,Nam, Donggeon,Shen, Zhuofan,Tinoco, Antonio
supporting information, p. 2590 - 2602 (2022/02/16)
The biocatalytic toolbox has recently been expanded to include enzyme-catalyzed carbene transfer reactions not occurring in Nature. Herein, we report the development of a biocatalytic strategy for the synthesis of enantioenriched α-trifluoromethyl amines through an asymmetric N-H carbene insertion reaction catalyzed by engineered variants of cytochrome c552 from Hydrogenobacter thermophilus. Using a combination of protein and substrate engineering, this metalloprotein scaffold was redesigned to enable the synthesis of chiral α-trifluoromethyl amino esters with up to >99% yield and 95:5 er using benzyl 2-diazotrifluoropropanoate as the carbene donor. When the diazo reagent was varied, the enantioselectivity of the enzyme could be inverted to produce the opposite enantiomers of these products with up to 99.5:0.5 er. This methodology is applicable to a broad range of aryl amine substrates, and it can be leveraged to obtain chemoenzymatic access to enantioenriched β-trifluoromethyl-β-amino alcohols and halides. Computational analyses provide insights into the interplay of protein- and reagent-mediated control on the enantioselectivity of this reaction. This work introduces the first example of a biocatalytic N-H carbenoid insertion with an acceptor-acceptor carbene donor, and it offers a biocatalytic solution for the enantioselective synthesis of α-trifluoromethylated amines as valuable synthons for medicinal chemistry and the synthesis of bioactive molecules.
Rh(III)-Catalyzed Regio- and Chemoselective [4 + 1]-Annulation of Azoxy Compounds with Diazoesters for the Synthesis of 2H-Indazoles: Roles of the Azoxy Oxygen Atom
Long, Zhen,Wang, Zhigang,Zhou, Danni,Wan, Danyang,You, Jingsong
supporting information, p. 2777 - 2780 (2017/06/07)
A Rh(III)-catalyzed tandem C-H alkylation/intramolecular decarboxylative cyclization of azoxy compounds with diazoesters for the synthesis of 3-acyl-2H-indazoles is disclosed. The azoxy instead of the azo group enables a distinct approach for cyclative capture, leading to a [4 + 1]-annulation rather than a classic [4 + 2] manner. The azoxy oxygen atom is traceless after annulation, and further removal from the product is not required. This reaction features a complete regioselectivity for unsymmetrical azoxybenzenes and a compatibility of monoaryldiazene oxides.
Rapid access to α-alkoxy and α-amino acid derivatives through safe continuous-flow generation of diazoesters
Bartrum, Hannah E.,Blakemore, David C.,Moody, Christopher J.,Hayes, Christopher J.
supporting information; experimental part, p. 9586 - 9589 (2011/10/08)
Microreactors: A highly efficient continuous-flow process has been developed for the synthesis of diazoesters from arylsulfonylhydrazones by means of in-flow Bamford-Stevens reactions. Furthermore, a range of α-alkoxy and α-amino acid derivatives have bee
CETP INHIBITORS
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Page/Page column 48, (2008/06/13)
Compounds of Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis. I
Ethyl 3-Trifluoro-2-diazo-propionate as a Potentially Useful CF3-containing Building Block: Preparation and 2-Catalysed Reaction with Nitriles
Shi, Guoqiang,Xu, Yuanyao
, p. 607 - 608 (2007/10/02)
A novel CF3-containing building block, ethyl 3-trifluoro-2-diazo-propionate, was easily prepared and reacted readily with nitriles in the presence of rhodium acetate to afford CF3-substituted oxazoles.
