Radical Carboxylative Cyclizations and Carboxylations with CO₂

Abstract

Metrics & MoreArticle Recommendations CONSPECTUS: Carbon dioxide (CO 2 ) is not only a greenhouse gas and a common waste product but also an inexpensive, readily available, and renewable carbon resource. It is an important one-carbon (C1) building block in organic synthesis for the construction of valuable compounds. However, its utilization is challenging owing to its thermodynamic stability and kinetic inertness. Although significant progress has been achieved, many limitations remain in this field with regard to the substrate scope, reaction system, and activation strategies. Since 2015, our group has focused on CO 2 utilization in organic synthesis. We are also interested in the vast possibilities of radical chemistry, although the high reactivity of radicals presents challenges in controlling selectivity. We hope to develop highly useful CO 2 transformations involving radicals by achieving a balance of reactivity and selectivity under mild reaction conditions. Over the past 6 years, we along with other experts have disclosed radical-type carboxylative cyclizations and carboxylations using CO 2 .We initiated our research by realizing the Cu-catalyzed radical-type oxytrifluoromethylation of allylamines and heteroaryl methylamines to generate valuable 2-oxazolidones with various radical precursors. Apart from Cu catalysis, visible-light photoredox catalysis is also a powerful method to achieve efficient carboxylative cyclization. In these cases, single-electron-oxidation-promoted C−O bond formation between benzylic radicals and carbamates is the key step. Since carboxylic acids exist widely in natural products and bioactive drugs and serve as important bulk chemicals in industry, we realized further visible-light-promoted carboxylations with CO 2 to construct such chemicals. We have achieved the selective umpolung carboxylations of imines, enamides, tetraalkylammonium salts, and oxime esters by successive single-electron-transfer (SSET) reduction. Using this strategy, we have also realized the dearomative arylcarboxylation of indoles with CO 2 . In addition to the incorporation of 1 equiv of CO 2 per substrate, we have recently developed a visible-light photoredox-catalyzed dicarboxylation of alkenes, allenes, and (hetero)arenes via SSET reduction, which allows the incorporation of two CO 2 molecules into organic compounds to generate valuable diacids as polymer precursors.In addition to the two-electron activation of CO 2 , we sought to develop new strategies to realize efficient and selective transformations via single-electron activation of CO 2 . Inspired by the hypothetical electron-transfer mechanism of iron−sulfur proteins, we have realized the visible-light-driven thiocarboxylation of alkenes with CO 2 using catalytic iron salts as promoters. The in-situ-generated Fe/S complexes are likely able to reduce CO 2 to its radical anion, which could react with alkenes to give a stabilized carbon radical. Moreover, we have also disclosed charge-transfer complex (CTC) formation between thiolate and acrylate/styr...

Desulfonylative Electrocarboxylation with Carbon Dioxide

“…1 H NMR (500 MHz, chloroform-d): δ 7.66 (dd, J = 8.3, 1.4 Hz, 2H), 7.61 (t, J = 7.5 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H), 6.94 (s, 1H), 6.67 (s, 2H), 4.22 (s, 2H), 2.21 (s, 6H). 13 3-[(Phenylsulfonyl)methyl]thiophene (S19). Isolated as a white solid in 92% yield (438 mg).…”

“…1 H NMR (500 MHz, chloroform-d): δ 7.67−7.64 (m, 2H), 7.63−7.59 (m, 1H), 7.49−7.44 (m, 2H), 7.25 (dd, J = 5.0, 3.0 Hz, 1H), 7.02 (dd, J = 3.0, 1.2 Hz, 1H), 6.90 (dd, J = 4.9, 1.3 Hz, 1H), 4.37 (s, 2H). 13 [(2-Phenylallyl)sulfonyl]benzene (S20). 59 Isolated as a white solid in 71% yield (1831 mg).…”

“…1 H NMR (400 MHz, chloroform-d): δ 7.52 (t, J = 7.1 Hz, 1H), 7.39−7.22 (m, 9H), 1.82 (s, 6H). 13 [4-Methyl-2-(phenylsulfonyl)pent-4-en-2-yl]benzene (S26). Isolated as a light yellow solid in 43% yield (129 mg).…”

“…1 H NMR (500 MHz, chloroform-d): δ 7.49 (ddp, J = 9.2, 5.9, 2.9 Hz, 1H), 7.41− 7.36 (m, 2H), 7.32−7.27 (m, 7H), 7.24 (t, J = 7.4 Hz, 2H), 4.79 (t, J = 1.8 Hz, 2H), 3.40 (d, J = 14.0 Hz, 1H), 3.00 (d, J = 14.0 Hz, 1H), 1.69 (s, 3H), 1.30 (s, 3H). 13 [(1-Phenylcyclopent-3-en-1-yl)sulfonyl]benzene (S27). Isolated as a white solid in 31% yield (88 mg).…”

“…Various fluorine-containing substrates, such as CF 3 (10), OCF 3 (11), and partially fluorinated (12) aromatics, could be easily converted to their corresponding arylacetic acid derivatives. The mild reaction conditions further allowed a multitude of functionalities, including cyano (13), ester ( 14), vinyl ester (15), vinyl (16), and Bpin (17), to survive. 2-(Naphthalen-2-yl)acetic acid (18), 2-(thiophen-3-yl)acetic acid (19), and 3-methylbut-3-enoic acid (20) were all readily obtained from their corresponding phenylsulfones.…”