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Samarium iodide-mediated C–C bond formation in the total synthesis of natural products

Nature Synthesis volume 1, pages 275–288 (2022)Cite this article

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Abstract

Since its introduction by Kagan more than 40 years ago, samarium(ii) iodide (SmI2; Kagan’s reagent) has found copious applications in organic synthesis. Its inherent strong reducing ability, together with external additives, enable tunable reactivity and endow SmI2 with powerful reactivity and impressive chemoselectivity. As a result, SmI2 has been broadly applied in a wide range of useful transformations, especially those involving C–C bond formation, in which both radical and ionic pathways could be selectively accessible. In the total synthesis of natural products, the versatility of SmI2 renders it more appealing than other single-electron reductants, particularly when used in key steps at the late stages of synthetic routes. Moreover, its ability to reach previously unattainable C–C bond disconnections accelerates the development of new synthetic strategies. In this Review, we highlight selected examples of SmI2-mediated C–C bond formation in the total synthesis of natural products reported from 2014 to 2021.

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Fig. 1: C–C bond formation between ketyl radicals and unactivated alkenes in total synthesis.
Fig. 2: Total synthesis of (−)-arcutinine, aplykurodinone-1 and jiadifenolide using ketyl radical–alkene coupling as key steps.
Fig. 3: Applications of SmI2-mediated 1,4-addition of ketyl radicals from aldehydes in the synthesis of (−)-haliclonin A, plumisclerin A and (+)-astellatol.
Fig. 4: Intramolecular carbonyl-activated alkene coupling to access natural products.
Fig. 5: Formation of crucial C–C bonds by carbonyl-activated alkene reductive coupling.
Fig. 6: SmI2-mediated pinacol-type coupling in the total synthesis of (−)-actinophyllic acid, manginoid A, Taxol and Kopsia alkaloids.
Fig. 7: The formation of C–C bonds via alkyl radicals.
Fig. 8: Total synthesis of natural products using imine-type intermediates and ionic processes.

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Acknowledgements

Financial support of this research from the Chinese Academy of Sciences (supported by the Strategic Priority Research Program, grant XDB20020200 and QYZDJ-SSW-SLH029) and the National Natural Science Foundation of China (grants 21132008, 21831009 and 21991110) is acknowledged.

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  1. State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China

    Yang Gao & Dawei Ma

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Y.G. and D.M. contributed to discussions and wrote the manuscript.

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Gao, Y., Ma, D. Samarium iodide-mediated C–C bond formation in the total synthesis of natural products. Nat. Synth 1, 275–288 (2022). https://doi.org/10.1038/s44160-022-00046-z

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