Nucleophilic addition to carbonyl compounds is one of the most fundamental transformations in organic synthesis. Carbonyl carbon atoms serve as electrophilic carbinol cation synthons in reactions with nucleophiles. Umpolung of the carbonyl reactivity should permit carbonyl compounds to react as nucleophilic carbinol anions with electrophiles. We have developed photocatalytic umpolung reactions of carbonyl compounds to generate anionic carbinol synthons through multielectron reduction. Here two approaches are presented. The first approach exploits carbon dioxide-promoted electron transfer (CO2ET) process. Under photocatalytic conditions in the presence of CO2, aromatic aldehydes and ketones undergo two-electron reduction to generate carbinol anion equivalents. The resulting nucleophilic species participate in a range of C-C bond forming reactions, including carboxylation, cross-pinacol coupling with second carbonyl compounds, and 1,4-addition to electron-deficient olefins. This concept is further extended to α,β-unsaturated carbonyl compounds, where homoenolate anion equivalents are generated through CO2ET process. The second approach relies on a newly developed diazabenzacenaphthenium photocatalyst (N-BAP) with high photoredox abilities and visible-light absorption. In combination with ammonium oxalate as a traceless reductant, N-BAP promotes unprecedented four-electron reduction of esters to generate carbinol anion equivalents. The resulting carbinol anions undergo protonation to afford alcohols and react nucleophilically with carbonyl electrophiles to form unsymmetric 1,2-diols.
Okumura et al. (Wed,) studied this question.