5905-69-1Relevant articles and documents
Regio- and chemoselectivity in S- and O- difluoromethylation reactions using diethyl (bromodifluoromethyl)phosphonate
Amir, Dafna,Binyamin, Iris,Drug, Eyal,Fridkin, Gil,Gershonov, Eytan,Marciano, Daniele,Redy-Keisar, Orit,Yehezkel, Lea,Zafrani, Yossi
, (2021/09/08)
The effective difluoromethylations of various S- and O- based- nucleophiles, presenting a wide range of pKa values, using diethyl(bromodifluoromethyl) phosphonate (1) under basic conditions is described. These reactions, which rely on the quantitative generation of difluorocarbene formed through the hydrolysis of 1, were found to be effective only once the starting materials had pKa values of less than ca. 11. Importantly, in cases in which the substrates held two or three nucleophilic centers this feature was successfully implemented to achieve a high chemo- or regioselective difluoromethylation of the center exhibiting the lowest pKa value and the highest polarizability.
Catalytic radical difluoromethoxylation of arenes and heteroarenes
Lee, Johnny W.,Zheng, Weijia,Morales-Rivera, Cristian A.,Liu, Peng,Ngai, Ming-Yu
, p. 3217 - 3222 (2019/03/21)
Intermolecular C-H difluoromethoxylation of (hetero)arenes remains a long-standing and unsolved problem in organic synthesis. Herein, we report the first catalytic protocol employing a redox-active difluoromethoxylating reagent 1a and photoredox catalysts for the direct C-H difluoromethoxylation of (hetero)arenes. Our approach is operationally simple, proceeds at room temperature, and uses bench-stable reagents. Its synthetic utility is highlighted by mild reaction conditions that tolerate a wide variety of functional groups and biorelevant molecules. Experimental and computational studies suggest single electron transfer (SET) from excited photoredox catalysts to 1a forming a neutral radical intermediate that liberates the OCF2H radical exclusively. Addition of this radical to (hetero)arenes gives difluoromethoxylated cyclohexadienyl radicals that are oxidized and deprotonated to afford the products of difluoromethoxylation.
Difluoromethylation of Phenols and Thiophenols with the S-(Difluo-romethyl)sulfonium Salt: Reaction, Scope, and Mechanistic Study
Liu, Guo-Kai,Qin, Wen-Bing,Li, Xin,Lin, Li-Ting,Wong, Henry N. C.
, p. 15948 - 15957 (2019/11/16)
A facile and practical approach for the difluoromethylation of phenols and thiophenols was described. Making use of the recently developed bench-stable S-(difluoromethyl)sulfonium salt as the difluorocarbene precursor, a wide variety of diversely functionalized phenols and thiophenols were readily converted to their corresponding aryl difluoromethyl ethers in good to excellent yields in the presence of lithium hydroxide. Chemoselectivity of various O,S-nucleophiles toward difluorocarbene was systematically studied, suggesting the reactivity order ArS- > RS-, ArO- > ROH > RO-, ArSH, ArOH, RSH.
