Copper-Catalyzed Carboxylation of C–F Bonds with CO₂

Abstract

An effective Cu-catalyzed selective formal carboxylation of C–F bonds with an atmospheric pressure of CO2 is reported. A variety of gem-difluoroalkenes, gem-difluorodienes, and α-trifluoro-methyl alkenes show high reactivity and selectivity for this ipso monocarboxylation. Under mild conditions, diverse important α-fluoroacrylic acids and α,α-difluorocarboxylates are obtained in good-to-high yields. Moreover, this operationally simple protocol features good functional group tolerance, is readily scalable, and the resulting products are readily converted into bioactive α-fluorinated carbonyl compounds, indicating potential application in biochemistry and drug discovery. Mechanistic studies reveal that fluorinated boronate esters might be vital intermediates in this transformation.

Carboxylation of Alkenyl Boronic Acids and Alkenyl Boronic Acid Pinacol Esters with CO2 Catalyzed by Cuprous Halide

“…[3e] In 2010, Lin and Marder disclosed the DFT studies of the carboxylation reactions of arylboronate esters with CO 2 catalyzed by (NHC)Cu (I) complexes, affirming the basic mechanistic proposal in Hou's work. [3h]…”

“…The earliest work was the rhodium‐catalyzed carboxylation of aryl‐ and alkenyl boronic esters with CO 2 reported by Iwasawa in 2006 . Since then, many similar transition metal‐catalyzed carboxylation of organoboronates with CO 2 have been reported using Cu, Ag, Ni catalysts. In almost all of these cases, the C(sp 2 )–B bond was carboxylated with CO 2 , except in one case where the alkyl C(sp 3 )–B bond was carboxylated with CO 2 .…”

“…In the carboxylation of C(sp 2 )–B bond with CO 2 , alkenyl boronic acid esters are used as substrates, especially alkenyl 5,5‐dimethyl‐1,3,2‐dioxaborinane (‐Bneop),, [3g], [3h], [4b], and only two cases used alkenyl boronic acid pinacol esters (‐Bpin)[3c], [3f] with only one example each (Scheme a). These two reactions aim to afford [ 11 C]‐labeled carboxylic acids with direct application of [ 11 C]CO 2 .…”

“…Based on our previous work,[3b] we further examined the carboxylation of alkenyl boric acids and alkenyl boronic acid pinacol esters to expand the organoboron substrates on the incorporation of CO 2 . Herein, we report a simple and efficient cuprous halide catalyzed system for the carboxylation of three kinds of alkenyl boron compounds (Scheme c), with the advantage of mild conditions, simple operation, good functional group compatibility, and high yields.…”

Recent Advances in Transition Metal‐Catalyzed Functionalization of gem‐Difluoroalkenes

“…[14] Depending upon the electronic character of the gem-difluoroalkene, two distinct boron-based reagents were used. Bor- ylation of gem-difluoroalkenes (15) bearing an electrondeficient aryl groups occurred using (Bpin) 2 , while gemdifluoroalkenes with an electron-rich aryl groups occurred using (Bnep) 2 . Moreover, the (fluoroalkenyl)-boronic ester products (16 or 16') were further derivatized to afford the corresponding potassium trifluoroborate salts (17) by reacting with KHF 2 in MeOH.…”