Photocatalytic Carbinol Cation/Anion Umpolung: Direct Addition of Aromatic Aldehydes and Ketones to Carbon Dioxide

Abstract

We have developed a new photocatalytic umpolung reaction of carbonyl compounds to generate anionic carbinol synthons. Aromatic aldehydes or ketones reacted with carbon dioxide in the presence of an iridium photocatalyst and 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzimidazole (DMBI) as a reductant under visible-light irradiation to furnish the corresponding α-hydroxycarboxylic acids through nucleophilic addition of the resulting carbinol anions to electrophilic carbon dioxide.

Photocatalytic Cross-Pinacol Coupling

“…4a). 23 To rule out a radical-radical coupling pathway, we confirmed the inertness of the electron-rich aldehydes and ketones undecanal (2H), 4fluoroacetophenone (2M), and acetophenone (2N) under the standard conditions (Fig. 4b and SI, Table S9).…”

“…Surprisingly, when the reaction was carried out under a CO2 atmosphere, the cross-pinacol selectivity markedly improved, and 3aA was obtained in 77% NMR yield, along with a 7% yield of the homo-coupled dimer 4aa and a 9% yield of the ahydroxycarboxylic acid 6a (entry 2). 23 The presence of a small amount of CO2 (1 mL) was enough to promote cross-pinacol coupling, without the formation of the carboxylic acid 6a as a byproduct, giving 3aA in 67% yield together with a 13% yield of the homo-coupled product 4aa (entry 3). By a thorough screening of the reaction conditions, the NMR yield of 3aA was eventually increased to 82% along with 5% of diol 4aa when CO2 (5 mL) was bubbled through the solution for 30 seconds before irradiation under a N2 atmosphere; none of the a-hydroxycarboxylic acid 6a (entry 4) was formed [also see Table S5 in the Supplementary Information (SI) for details].…”

“…1b). 23 In this reaction, the carbonyl substrates underwent successive one-electron reduction under blue-light irradiation in the presence of an iridium photoredox catalyst and a 1,3-dimethyl-2,3-dihydro-1H-benzimidazole-based reductant 24,25 to generate nucleophilic carbinol anion species that subsequently reacted with carbon dioxide to afford the corresponding carboxylation products. If the inherent electrophilic nature of carbonyl groups is taken into account, the photocatalytic process brought about an umpolung of the carbonyls serving as nucleophilic carbinol synthons.…”

Recent advancements in visible-light-driven carboxylation with carbon dioxide

“…In the same year, Uozumi and Okumura disclosed a novel pathway when utilizing a photocatalytic umpolung strategy for the carboxylation of aromatic aldehydes and ketones in the presence of a photocatalyst and a reductant (DMBI) (Scheme 14). 25 Mechanistically, Stern–Volmer quenching experiments revealed that DMBI quenched the photocatalyst in an excited state. Ketyl radical 32 possibly coupled with CO 2 and was then-reduced by the strong reductant DMBI radical species 37 to give the key intermediate carbinol anionic species 34 .…”

Basicity as a Thermodynamic Descriptor of Carbanions Reactivity with Carbon Dioxide: Application to the Carboxylation of α,β-Unsaturated Ketones

“…This second possibility includes reductive activation of C-LG bonds (LG – is a leaving group, often a halide ion) ( Meng et al, 2017 ; Isse et al, 1998 ; Isse et al, 2002 ; Isse and Gennaro, 2002 ; Scialdone et al, 2008 ; Durante et al, 2013 ) of C=C or C=N double bonds ( Seo et al, 2017 ; Fan et al, 2018 ; Chen et al, 2020 ; Fan et al, 2018 ; Schmalzbauer et al, 2020 ) and of C-H bonds ( Gui et al, 2017 ; Seo et al, 2017 ; He et al, 2020 ). Recent examples include activation of substituted olefins ( Alkayal et al, 2020 ), of diverse carbonyl compounds ( Okumura and Uozumi, 2021 ) including α-ketoamides and α-ketoesters ( Cao et al, 2021 ), α,β-unsaturated esters ( Sheta et al, 2021 ) and ketones ( Chen et al, 2020 ), and of aldimines generated in situ for α-aminoacid synthesis ( Naito et al, 2021 ).…”