Over the past decades, many efficient methodologies have been developed that allow for the enantioselective synthesis of chiral sulfinyl compounds. However, the enantioselective deoxygenation of hexavalent sulfones for the formation of chiral sulfinyl compounds still remains one of the major challenges in the fields of asymmetric synthesis and organosulfur chemistry. Here we have demonstrated that a synergistic combination of organocatalysis and the incorporation of a cyano group into the sulfone generates a chiral sulfinic species as an active intermediate. A wide range of chiral sulfinates with high enantioselectivities could then be acquired using alcohols as nucleophiles, and the subsequent transformations allowed the collective preparation of a variety of chiral sulfinyl compounds. Density functional theory calculations revealed that the catalytic cycle involves a quinuclidine-assisted stepwise 1,2-cyano group transfer, base-assisted intermolecular substitution with alcohol and regeneration of the active catalyst. The enantioselectivity was determined by the cyano migration step.
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All relevant data supporting the findings of this study, including experimental procedures and compound characterization, NMR and HPLC are available within the Article and its Supplementary Information. Crystallographic data for the structures reported in this Article have been deposited at the Cambridge Crystallographic Data Centre under deposition numbers CCDC 1941245 (P3e), 2141490 ((R)-5) and 2141488 ((S)-11). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. Source data are provided with this paper.
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This study was supported by the Fundamental Research Funds for the Central Universities (grants: 2021CDJQY-035 to W.Q. and 2022CDJXY-025 to S.H.), the National Natural Science Foundation of China (grants: 21901026 to W.Q. and 21922101 to H.Y.) and the Natural Science Foundation of Chongqing (grant: cstc2021jcyj-jqX0019 to H.Y.).
The authors declare no competing interests.
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Supplementary Tables 1–5, Figs. 1–26, experimental data, synthesis and characterization data, NMR spectra, X-ray crystallographic data and DFT calculation data.
Supplementary Data 1
Crystallographic data for compound P3e; CCDC reference 1941245.
Supplementary Data 2
Crystallographic data for compound (R)-5; CCDC reference 2141490.
Supplementary Data 3
Crystallographic data for compound (S)-11; CCDC reference 2141488.
Supplementary Data 4
Cartesian coordinates for all optimized structures.
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Huang, S., Zeng, Z., Zhang, N. et al. Organocatalytic asymmetric deoxygenation of sulfones to access chiral sulfinyl compounds. Nat. Chem. 15, 185–193 (2023). https://doi.org/10.1038/s41557-022-01120-x
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