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0 202605029

DOI: https://doi.org/10.6023/cjoc202605029

ARTICLE

Application of Amide Reductive Alkynylation and Reductive Alkylation in the Rapid Synthesis of Schwarzinicines A-C and Ficusnotins B/F

  • Chen Jinquan ,
  • Huang Peiqiang
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  • Department of Chemistry and Fujian Key Laboratory of Chemical Biology (Xiamen University), College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005

Received date: 2026-05-29

  Revised date: 2026-07-07

  Online published: 2026-07-24

Supported by

National Natural Science Foundation of China (Nos. 22571267 and 21931010).

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Abstract

Ficusnotins B and F, along with schwarzinicines A, B, and C, are 1,4-diarylbutanoids reported in recent years. Despite their simple structure, structure-activity relationship studies have led to the identification of a lead compound for vasodilation. This article reports the application of two reactions previously developed by Huang’s group—reductive alkynylation and reductive alkylation of amides—in the synthesis of these five natural products. (1) A two-step synthesis of schwarzinicines A and C was established through iridium-catalyzed hydrosilylation of secondary amides followed by in situ Grignard addition, yielding two alkaloids in overall yields of 74% and 75%, respectively. (2) A "two-pot" synthesis of schwarzinicine B was achieved using the iridium-copper relay-catalyzed reductive alkynylation of tertiary amide followed by tandem palladium-catalyzed hydrogenation, resulting in the formation of the alkaloid with an overall yield of 79%. (3) By applying the latter method, a three-step synthesis of ficusnotins B and F was developed with overall yields of 75% and 68%, respectively. (4) Using iridium-copper and organocatalyst relay/synergistic catalysis, a two-step catalytic asymmetric synthesis of schwarzinicines A, B, and C was preliminarily developed. Although the enantioselectivities were only 2.4: 1, 2: 1, and 2.4: 1, respectively, the enantiomerically enriched products thus obtained enabled us to tentatively assign the previously unknown absolute configurations of schwarzinicines A, B, and C.

Key words： Natural products; Total synthesis; Reductive alkynylation of amides; Reductive alkylation of amides; Absolute configuration

Cite this article

Chen Jinquan , Huang Peiqiang . Application of Amide Reductive Alkynylation and Reductive Alkylation in the Rapid Synthesis of Schwarzinicines A-C and Ficusnotins B/F[J]. Chinese Journal of Organic Chemistry, 0 : 202605029 . DOI: 10.6023/cjoc202605029

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