365-01-5Relevant articles and documents
Kinetics of Electrophilic Fluorinations of Enamines and Carbanions: Comparison of the Fluorinating Power of N-F Reagents
Timofeeva, Daria S.,Ofial, Armin R.,Mayr, Herbert
, p. 11474 - 11486 (2018)
Kinetics of the reactions of enamines and carbanions with commonly used fluorinating reagents, N-fluorobenzenesulfonimide (NFSI), N-fluoropyridinium salts, Selectfluor, and an N-fluorinated cinchona alkaloid, have been investigated in acetonitrile. The reactions follow second-order kinetics, and from the measured rate constants one can derive that the fluorinations proceed via direct attack of the nucleophiles at fluorine, not by SET processes. Correlations of the fluorination rates with the pKaH values of the nucleofugal leaving groups and the calculated fluorine plus detachment energies are discussed. The rate constants for the reactions with deoxybenzoin-derived enamines follow the linear free energy relationship log k2(20 °C) = sN(N + E) which allows the empirical electrophilicity parameters E for these fluorinating agents to be derived from the measured rate constants and the tabulated N and sN parameters for the nucleophiles. Though the deviations of the measured rate constants from those calculated by this relationship are larger than for reactions of Csp2-centered electrophiles with nucleophiles, it is shown that the electrophilicity parameters E reported in this work are able to rationalize known fluorination reactions and are, therefore, recommended as guide for designing new electrophilic fluorinations.
Bench-Stable Electrophilic Fluorinating Reagents for Highly Selective Mono- and Difluorination of Silyl Enol Ethers
Adachi, Akiya,Aikawa, Kohsuke,Ishibashi, Yuichiro,Nozaki, Kyoko,Okazoe, Takashi
supporting information, p. 11919 - 11925 (2021/07/02)
Efficient methods for the synthesis of fluorinated compounds have been intensively studied, recently. Development of practical fluorinating reagents is indispensable for this purpose. Herein, bench-stable electrophilic fluorinating reagents were synthesized as N-fluorobenzenesulfonimide (NFSI) substitutes. Reagents obtained by replacing one of the NFSI sulfonyl groups with an acyl group led to the highly selective monofluorination of silyl enol ethers with suppression of undesired overreaction, that is, difluorination. On the other hand, reagents bearing electron-withdrawing substituents at NFSI benzenesulfonyl groups efficiently facilitated the difluorination of silyl enol ethers under base-free conditions. Thus, both mono- and difluorinated target materials were prepared from the same substrate.
Development and Mechanistic Investigations of a Base-Free Suzuki-Miyaura Cross-Coupling of α,α-Difluoroacetamides via C-N Bond Cleavage
Amgoune, Abderrahmane,Bouyssi, Didier,Jeanneau, Erwann,Krachko, Tetiana,Monteiro, Nuno,Onida, Killian,Reina, Antonio
, p. 2189 - 2197 (2020/02/28)
This study describes the development and understanding of a palladium-catalyzed cross-coupling of fluoroacetamides with boronic acids, under base-free conditions, to selectively give valuable α,α-difluoroketone derivatives. Detailed mechanistic studies were conducted to assess the feasibility of each elementary step, that is, C(acyl)-N bond oxidative addition, followed by base-free transmetallation and reductive elimination. These investigations allowed the structural characterization of palladium(II)fluoroacyl intermediates derived from C-N bond oxidative addition of an amide electrophile. They also revealed the high reactivity of these intermediates for transmetallation with boronic acids without exogenous base. The mechanistic studies also provided a platform to design a practical catalytic protocol for the synthesis of a diversity of α,α-difluoroketones, including CF2H-ketones. Finally, the synthetic potential of this fluoroacylation methodology is highlighted in sequential, orthogonal C-Br and C-N bond functionalization of an α-bromo-α,α-difluoroacetamide with a focus on compounds of potential biological relevance.
