New methodology for difluoromethylation and difluoromethylenation of aldehydes and ketones based on nucleophilic fluorination using diethyl difluoromethylphosphonate (1) was developed.
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http://dx.doi.org/10.1016/j.tet.2008.10.006 | DOI Listing |
J Org Chem
September 2024
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P. R. China.
Herein, we report a simple and versatile difluoromethylene-imide reaction in which a series of olefins can undergo a difluoromethylenimine reaction under photocatalytic conditions through an energy transfer (EnT) process. The reaction has mild conditions and a wide range of applicability. We successfully synthesized 27 molecules containing difluoromethylene units, featuring easily accessible starting materials and operational simplicity.
View Article and Find Full Text PDFJ Org Chem
September 2024
Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China.
The incorporation of gem-difluoromethylene units into organic molecules remains a formidable challenge. Conventional methodologies for constructing aryldifluoromethyl derivatives relied on the use of high-functional fluorinating regents under harsh conditions. Herein, we report general and efficient photoredox catalytic systems for defluoroalkylation of readily available trifluoromethylarenes through selective C-F cleavage to deliver gem-difluoromethyl radicals which proceed through reductive addition to both electron-donating and withdrawing alkenes under transition-metal free conditions.
View Article and Find Full Text PDFJ Am Chem Soc
June 2024
Department of Chemistry, University of California, Berkeley, California 94720, United States.
Acc Chem Res
March 2024
Key Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032, China.
ConspectusAs fluorine has played an increasingly important role in modulating the physical, chemical, and biological properties of organic molecules, the selective introduction of fluorine atom(s) or fluorinated moieties into target molecules has become a powerful tool in the development of new pharmaceuticals, agrochemicals, and functional materials. In this context, the difluoromethylene (CF) and difluoromethyl (CFH) groups are of special interest because of their ability to serve as bioisosteres of ethereal oxygen atoms and hydroxyl (OH) and thiol (SH) groups, respectively. Difluorocarbene is one of the most versatile reactive intermediates to incorporate CF and CFH groups; however, before 2006, most of the previously known difluorocarbene reagents suffered from several drawbacks such as using ozone-depleting substances (ODSs), difficult-to-handle reagents, or harsh reaction conditions or having narrow substrate scope and/or low yields.
View Article and Find Full Text PDFThe introduction of difluoromethylene moieties into organic molecules has garnered significant attention due to their profound influence on the physicochemical and biological properties of compounds. Nonetheless, the existing approaches for accessing difluoroalkanes from readily available feedstock chemicals remain limited. In this study, we present an efficient and modular protocol for the synthesis of difluorinated compounds from alkenes, employing the readily accessible reagent, ClCFSONa, as a versatile "difluoromethylene" linchpin.
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