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

Abstract

Photoredox-mediated umpolung strategy provides an alternative pattern for functionalization of carbonyl compounds. However, general approaches towards carboxylation of carbonyl compounds with CO2 remain scarce. Herein, we report a strategy for visible-light photoredox-catalyzed umpolung carboxylation of diverse carbonyl compounds with CO2 by using Lewis acidic chlorosilanes as activating/protecting groups. This strategy is general and practical to generate valuable α-hydroxycarboxylic acids. It works well for challenging alkyl aryl ketones and aryl aldehydes, as well as for α-ketoamides and α-ketoesters, the latter two of which have never been successfully applied in umpolung carboxylations with CO2 (to the best of our knowledge). This reaction features high selectivity, broad substrate scope, good functional group tolerance, mild reaction conditions and facile derivations of products to bioactive compounds, including oxypheonium, mepenzolate bromide, benactyzine, and tiotropium. Moreover, the formation of carbon radicals and carbanions as well as the key role of chlorosilanes are supported by control experiments.

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

“…However, one of the major problems in reducing ketyl radicals lies in their high reactivity toward radical–radical coupling to form dimeric vicinal diols (Scheme B, left) . During the preparation of this manuscript, Yu and co-workers reported the photocatalytic generation of α-siloxy carbanions from aromatic carbonyl compounds, in which an oxygen anion of a ketyl radical intermediate was masked in situ by a sterically demanding silyl group to suppress radical–radical coupling (Scheme B, bottom). Clearly, although pioneering strides have been made, additional studies on the development of alternative carbinol umpolungs are warranted.…”

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

“…Based on the above discussion, some considerations of general relevance can be finally addressed and focused in particular on 1) the reactivity of radical anions, generated from a one-electron reduction of the parent C=C bond; this type of intermediate is often envisaged in photochemical carboxylation processes ( Nikolaitchik et al, 1996 ; Seo et al, 2017 ); 2) the reactivity of carbanions generated from an activation of C=O bonds, via an umpolung strategy ( Juhl and Lee, 2018 ; Juhl et al, 2019 ; Cao et al, 2021 ).…”

“…We finally verified if the model is suitable for the prediction of carboxylation of carbanions generated by activation of C=O groups through an umpolung strategy. In particular, we considered a carbanion of 4-fluorobenzaldehyde activated via a cyanohydrin intermediate ( Juhl and Lee, 2018 ) and the carbanions of alkyl aryl ketones, α-ketoesters, and aryl aldehydes generated through a photochemical process combining a trimethylsilyl (in the case of the alkyl aryl ketones and of α-ketoesters) or triphenylsilyl (in the case of aryl aldehydes) activating/protecting group, see Scheme 6 ( Cao et al, 2021 ). Gratifyingly, the calculations predict a negative ΔG 0 for the carboxylation of such intermediates ( Juhl et al, 2019 ), thus supporting the experimental outcome (see the yields of carboxylation in Scheme 6 ) ( Juhl and Lee, 2018 ; Cao et al, 2021 ).…”

“… Formation of carbanions capable of carboxylation reactions via Umpolung activation of C=O bonds. See references for further experimental conditions ( Juhl and Lee, 2018 ; Juhl et al, 2019 ; Cao et al, 2021 ). …”

“…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 ).…”