Visible-light photoredox-catalyzed umpolung carboxylation of carbonyl compounds with CO2

Photoredox-mediated umpolung strategy provides an alternative pattern for functionalization of carbonyl compounds. Here, we report a strategy for visible-light photoredox-catalyzed umpolung carboxylation of carbonyl groups with CO2 by using Lewis acidic chlorosilanes as activating/protecting groups.

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The research group of Prof. Da-Gang Yu at Sichuan  University  has  been  focusing  on the development of strategies for CO2 utilization and visible-light photoredox catalysis in the past few years. In    the    area    of    radical     carboxylative     cyclizations     and carboxylations with CO2 (key review: Acc. Chem. Res. 2021, 54, 2518.), we  have  chieved visible light-driven difluoroalkylation  and  alkylation  of  allylamines  (OL 2017, 20, 190; OL 2018, 20, 3049), difunctionalization carboxylation of π  system  (ACIE 2017, 56, 15416; Nat. Commun. 2019, 10, 3592; Nat. Commun. 2020, 11, 3263; ACIE  2020,  59,  21121;  JACS 2021, 143, 2812; Nat. Catal. 2021, 4, 304; SCC. 2021, https://doi.org/10.1007/s11426-021-1004-y) and anti-markovnikov hydrocarboxylation of alkene  (CCS Chem. 2020, 2, 1746). Also, we have achieved the  selective  umpolung  carboxylations  of  imines,  enamides, tetraalkylammonium salts, and  oxime  esters  via  successive  single-electron-transfer (SSET) reduction (ACIE 2018, 57, 13897; JACS 2018, 140, 17338;  ChemSusChem 2020,  13, 6312). In our recent paper published in  Nature  Communications,   we   described   the latest progress on this topic. Developing a general strategy for reductive carboxylation of carbonyl compounds with CO2 to give valuable alfa-hydroxycarboxylic  acids,  which are key intermediates to produce many drugs and natural products, including oxyphe-onium, mepenzolate bromide, benactyzine, and tiotropiumas.

Carbonyl compond are important bulk chemicals in industry and they  exist  widely  in natural products, pharmaceuticals, and materials. Recently, visible light-mediated SET umpolung reaction of carbonyl group has received intensive attention  owing  to  their mild reaction conditions and green processes1,2. In particular, photocatalytic  proton-coupled electron transfer (PCET)3 has evoked a new round of exploration  on  carbonyl chemistry, which can  achieve  ketyl−olefin  coupling  and  radical-radical  coupling   by generating ketyl radical. However, the direct radical addition of ketyl  radicals  to  CO2  is less favored4, a second SET reduction to generate a  carbanion,  which  could  attack electrophilic CO2,  would   be   promising.   However,   achieving  such  a  goal  requires avoiding  common  side  reactions,   namely   pinacol   coupling5   and   hydrogen   atom transfer (HAT)6 of ketyl radicals,  direct a-carboxylation, homo-aldol   and   Cannizzaro reaction  under basic  conditions.  With  such  challenges  in  mind,  we  were  inspired   by  PCET  and  hypothesized whether we could use a Lewis acidic chlorosilane instead of a proton as an activating group to promote the SET reduction of  a  carbonyl  group. Moreover, the activating chlorosilane might act  as  a  temporary  protecting  group  to generate alfa-silyloxy  carbon  radicals,  which  would  increase  the  steric   hindrance  of the radical intermediates and thus retard undesired pinacol coupling. Based  on  this design, we developed a general and practical method for the  carboxylation  of  diverse carbonyl  compounds,  including  alkyl  aryl  ketones,  diaryl ketones,   alfa-ketoamides, alfa-ketoesters,  and  aryl  aldehydes,  to  give  valuable  alfa-hydroxycarboxylic   acids.  And control experiments demonstrated the important role of chlorosilanes to promote the   reaction   and   carbon   radicals   and   carbanions   might   be   involved    in    this transformation.

More details of this work could be found   here:   “ Visible-light   photoredox-catalyzed umpolung carboxylation of carbonyl compounds with CO2” in Nature Communications (https://www.nature.com/articles/s41467-021-23447-8).

References

  1. Lee, K. N. & Ngai, M.-Y.  Recent  developments   in   transition-metal   photoredox-catalysed reactions of carbonyl derivatives. Chem. Commun. 53, 13093-13112 (2017).
  2. Xia, Q., Dong, J., Song, H. & Wang, Q.   Visible-Light   Photocatalysis   of   the   Ketyl Radical Coupling Reaction. Chem. Eur. J. 25, 2949-2961 (2019).
  3. Gentry, E. C. & Knowles, R. R. Synthetic  Applications  of  Proton-Coupled  Electron Transfer. Acc. Chem. Res. 49, 1546-1556 (2016).
  4. Isse, A. A. & Gennaro, A.   Mechanism  of    the   Electrochemical   Carboxylation   of Aromatic Ketones in Dimethylformamide. Collect. Czech. Chem. Commun. 68, 1379-1394 (2003).
  5. Nakajima, M., Fava, E., Loescher, S., Jiang, Z. & Rueping, M.    Photoredox-Catalyzed Reductive Coupling of Aldehydes, Ketones, and Imines  with  Visible Light.  Angew. Chem. Int. Ed. 54, 8828-8832 (2015).
  6. Ishitani, O., Yanagida, S., Takamuku, S. & Pac, C. Redox-photosensitized reactions. Ru(bpy)32+-photosensitized reactions of an NADH model,                      1-benzyl-1,4-dihydronicotinamide, with  aromatic  carbonyl  compounds  and  comparison  with thermal reactions. J. Org. Chem. 52, 2790-2796 (1987).

Da-Gang Yu

Professor, Sichuan University