The synthesis of highly functionalized monofluorinated cyclopropanes based on a Michael Initiated Ring Closure (MIRC) reaction has been developed. The addition of quaternary ammonium salts derived from ethyl bromofluoroacetate on a panel of electron deficient alkenes followed by cyclization gave rise to an efficient access to monofluorinated cyclopropanes with good yields and remarkable diastereoselectivity.
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http://dx.doi.org/10.1021/ol402837u | DOI Listing |
Angew Chem Int Ed Engl
August 2024
Department of Chemistry and Biochemistry, University of Texas at Dallas, 800 W. Campbell Road, Richardson, TX 75080, United States.
Fluorinated cyclopropanes are highly desired pharmacophores in drug discovery owing to the rigid nature of the cyclopropane ring and the beneficial effects of C-F bonds on the pharmacokinetic properties, cell permeability, and metabolic stability of drug molecules. Herein a biocatalytic strategy for the stereoselective synthesis of mono-fluorinated and gem-difluoro cyclopropanes is reported though the use of engineered myoglobin-based catalysts. In particular, this system allows for a broad range of gem-difluoro alkenes to be cyclopropanated in the presence of diazoacetonitrile with excellent diastereo and enantiocontrol (up to 99 : 1 d.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
August 2023
West China School of Public Health and West China Fourth Hospital, West China-PUMC C.C. Chen Institute of Health, State Key Laboratory of Biotherapy, Sichuan University, 610041, Chengdu, China.
Direct synthesis of gem-difluorinated carbocyclic molecules represents a longstanding challenge in organic chemistry. Herein, a Rh-catalyzed [3+2] cycloaddition reaction between readily available gem-difluorinated cyclopropanes (gem-DFCPs) and internal olefins has been developed, enabling the efficient synthesis of gem-difluorinated cyclopentanes with good functional group compatibility, excellent regioselectivity and good diastereoselectivity. The resulting gem-difluorinated products can undergo downstream transformations to access various mono-fluorinated cyclopentenes and cyclopentanes.
View Article and Find Full Text PDFJ Org Chem
February 2021
Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia.
An investigation of the properties and reactivity of fluoromethylsulfonium salts resulted in the redesign of the reagents for fluoromethylene transfer chemistry. The model reaction, fluorocyclopropanation of nitrostyrene, turned out to be a suitable platform for the discovery of more streamlined fluoromethylene transfer reagents. The incorporation of halides on one aryl ring increased the reactivity, and 2,4-dimethyl substitution on the other aryl ring provided a balance between the reactivity/crystallinity of the reagent as well as the atom economy.
View Article and Find Full Text PDFOrg Lett
September 2019
Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia.
Diarylfluoromethylsulfonium salts, alternatives to freons or advanced fluorinated building blocks, are bench stable and easy-to-use sources of direct fluoromethylene (:CHF) transfer to alkenes. These salts enabled development of a -selective monofluorinated Johnson-Corey-Chaykovsky reaction with vinyl sulfones or vinyl sulfonamides to access synthetically challenging monofluorocyclopropane scaffolds. The described method offers rapid access to monofluorinated cyclopropane building blocks with further functionalization opportunities to deliver more complex synthetic targets diastereoselectively.
View Article and Find Full Text PDFOrg Lett
November 2013
Normandie Université, COBRA, UMR 6014 et FR 3038; Université de Rouen; INSA Rouen; CNRS, 1 rue Tesnière, 76821 Mont Saint-Aignan Cedex, France.
The synthesis of highly functionalized monofluorinated cyclopropanes based on a Michael Initiated Ring Closure (MIRC) reaction has been developed. The addition of quaternary ammonium salts derived from ethyl bromofluoroacetate on a panel of electron deficient alkenes followed by cyclization gave rise to an efficient access to monofluorinated cyclopropanes with good yields and remarkable diastereoselectivity.
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