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Counterintuitive chemoselectivity in the reduction of carbonyl compounds

Nature Reviews Chemistry volume 8, pages 518–534 (2024)Cite this article

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Abstract

The reactivity of carbonyl functional groups largely depends on the substituents on the carbon atom. Reversal of the commonly accepted order of reactivity of different carbonyl compounds requires novel synthetic approaches. Achieving selective reduction will enable the transformation of carbon resources such as plastic waste, carbon dioxide and biomass into valuable chemicals. In this Review, we explore the reduction of less reactive carbonyl groups in the presence of those typically considered more reactive. We discuss reductions, including the controlled reduction of ureas, amides and esters to aldehydes, as well as chemoselective reductions of carbonyl groups, including the reduction of ureas over carbamates, amides and esters; the reduction of amides over esters, ketones and aldehydes; and the reduction of ketones over aldehydes.

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Fig. 1: Selective transformation of carbonyl compounds.
Fig. 2: Selective hydrogenolysis of ureas.
Fig. 3: Reaction pathways of amide hydrogenation.
Fig. 4: Controlled and chemoselective reduction of amides through C–N bond cleavage.
Fig. 5: Controlled and chemoselective reduction of amides through C–O bond cleavage.
Fig. 6: Controlled reduction of esters to aldehydes.
Fig. 7: Chemoselective reduction of ketones over aldehydes.

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Acknowledgements

This work was supported by the Grant-in-Aid for Scientific Research(B) (Nos. JP23H01955 and JP23K26648) from the Japan Society for the Promotion of Science; the Grant-in-Aid for Transformative Research Areas (A) JP21A204 in Digitalization-driven Transformative Organic Synthesis (Digi-TOS) (Nos. JP22H05340 and JP24H01061) from the Ministry of Education, Culture, Sports, Science and Technology; JST ERATO (No. JPMJER2103) from the Japan Science and Technology Agency; Sumitomo Foundation; and Fujimori Science and Technology Foundation.

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    Takanori Iwasaki & Kyoko Nozaki

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Glossary

Hydrogenation

Reaction involving the addition of hydrogen gas (H2) to multiple bonds.

Hydrogenolysis

Bond cleavage reaction via addition of hydrogen gas (H2) to a carbon–heteroatom single bond.

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Iwasaki, T., Nozaki, K. Counterintuitive chemoselectivity in the reduction of carbonyl compounds. Nat Rev Chem 8, 518–534 (2024). https://doi.org/10.1038/s41570-024-00608-z

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