Abstract
Prenylation is a ubiquitous process common to almost all living organisms, and a key transformation in organic synthesis. Dearomative prenylation reactions of tryptophan derivatives lead to various prenylated indoline alkaloids with diverse biological activities. However, enantioselective dearomative prenylations without a pre-installed stereogenic centre in the substrate have not been reported. Here, we show that a small molecule-based catalytic system derived from a commercially available palladium precursor and a chiral phosphoramidite ligand (allylphos) can catalyse the enantioselective dearomative prenylation of indole derivatives, which tolerates a much broader substrate scope than those of known enzymatic dearomative prenylation processes. Enantioselective dearomative geranylation and farnesylation reactions also proceed smoothly under the standard conditions. The concise total or formal syntheses of a series of natural products can be realized using this catalytic system. The mechanistic investigations provide deep insights for the further design of chiral ligands and catalysts for asymmetric reactions.
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Acknowledgements
We thank the National Key Research and Development Program of China (2016YFA0202900), National Basic Research Program of China (973 Program 2015CB856600), National Natural Science Foundation of China (21332009 and 21572252), Strategic Priority Research Program (XDB20000000) and Key Research Program of Frontier Sciences (QYZDYSSWSLH012) of the Chinese Academy of Sciences, and the Science and Technology Commission of Shanghai Municipality (16XD1404300) for generous financial support, and X. Leng and J. Sun (SIOC) for X-ray crystallographic analysis.
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H.-F.T. and X.Z. were involved in the discovery, design and development of the enantioselective dearomative prenylation of indole derivatives. X.Z. synthesized allylphos. H.-F.T. performed the total syntheses of the natural products. H.-F.T. and C.Z. performed the mechanistic studies. M.Z. was involved in the synthesis of substrates. S.-L.Y. conceived and supervised the project. H.-F.T., C.Z. and S.-L.Y. wrote the manuscript with revisions suggested by all authors.
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Supplementary Methods, Supplementary Figures 1–3, Supplementary Tables 1–17, Supplementary References
Crystallographic data
CIF for compound C1; CCDC reference: 1822391
Crystallographic data
CIF for compound C2; CCDC reference: 1822392
Crystallographic data
CIF for compound 22; CCDC reference: 1822393
Crystallographic data
CIF for compound (R)-L1; CCDC reference: 1822394
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Tu, HF., Zhang, X., Zheng, C. et al. Enantioselective dearomative prenylation of indole derivatives. Nat Catal 1, 601–608 (2018). https://doi.org/10.1038/s41929-018-0111-8
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DOI: https://doi.org/10.1038/s41929-018-0111-8
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