Difluoroenol silyl ethers, produced in situ from acylsilanes and CF3TMS, react as electrophiles with amines to give difluoroimines, via the corresponding hemiaminal adduct, as evidenced by 19F NMR spectroscopy. Reaction with (R)-phenylglycinol led to 2-difluoromethyloxazolidines. After separation of the diastereomers, reduction with LAH and Strecker-type synthesis gave enantiopure alpha-difluoromethylamines and alpha-difluoromethyl-alpha-amino acids, respectively.
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http://dx.doi.org/10.1021/jo702328v | DOI Listing |
Org Lett
August 2022
Technical Institute of Fluorochemistry (TIF), Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, Jiangsu211816, China.
An efficient method for the synthesis of β,β-di(hetero)aryl-α,α-difluorinated ketones using readily available organophosphonium salts and difluoroenol silyl ethers has been developed. This mild reaction features a good functional group tolerance, a scaled-up synthesis, and synthetic simplicity. By taking advantage of DMSO as a less-toxic promoter and solvent for the difluoroalkylation and C-P bond functionalization, the use of transition-metal catalysts and sensitive additives could be avoided.
View Article and Find Full Text PDFChem Sci
February 2020
Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Zhejiang Normal University China
Herein we describe the dearomatization of aryl sulfoxides with difluoroenol silyl ether (DFESE) using a rearrangement/addition protocol. The selection of the sulfoxide activator determines whether one or two difluoroalkyl groups are incorporated into dearomatized products. Using TFAA can deliberately halt the reaction at the mono-difluoroalkylated dearomatized intermediate formed a [3,3]-rearrangement, which can be further trapped by external nucleophiles to give mono-difluoroalkylated alicycles.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
April 2019
Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Zhejiang Normal University, Jinhua, 321004, China.
Presented herein is an intriguing effect of fluorine, and it allows difluoroenol silyl ethers to couple with aryliodanes in a redox-neutral manner to afford ortho-iodo difluoroalkylated arenes. The remaining iodide group provides a versatile platform for converting the products into various valuable difluoroalkylated arenes. The reaction shows excellent functional-group compatibility and broad substrate scope.
View Article and Find Full Text PDFChem Commun (Camb)
May 2016
Chemical Engineering College, Nanjing University of Science and Technology, 200 Xiao Ling Wei Street, Nanjing, Jiangsu, People's Republic of China.
A mild and efficient method for the radical addition of α-aryl-β,β-difluoroenol silyl with arene diazonium tetrafluoroborates at room temperature has been disclosed, which involves an innate radical long chain cycle, so only a small amount (0.05 mol%) of photocatalyst and a short light exposure time are required as radical initiators. A proposed mechanism for the transformation is also illustrated based on the results of control experiments and quantum calculations.
View Article and Find Full Text PDFOrg Biomol Chem
December 2015
Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, 3663N, Zhongshan Road, Shanghai 200062, China.
Ph3PAuOTf is identified as a powerful catalyst for the addition of difluoroenol silyl ethers to N-Boc isatin ketimines and other two kinds of active cyclic ketimines. This represents the first Au(i)-catalyzed Mukaiyama-Mannich reaction, and the corresponding non-fluorinated enol silyl ether proves to be even much more reactive under the same conditions. This method paves the way to the total synthesis of difluoromethylated analogues of AG-041R, a gastrin/CCK-B receptor antagonist.
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