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Stereoretentive Pd-catalysed Stille cross-coupling reactions of secondary alkyl azastannatranes and aryl halides

Nature Chemistry volume 5, pages 607–612 (2013)Cite this article

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Abstract

The development of transition metal-catalysed cross-coupling reactions has greatly influenced the manner in which the synthesis of complex organic molecules is approached. A wide variety of methods are now available for the formation of C(sp2)–C(sp2) bonds, and more recent work has focused on the use of C(sp3) electrophiles and nucleophiles. The use of secondary and tertiary alkyl nucleophiles in cross-coupling reactions remains a challenge because of the propensity of these alkyl groups to isomerize under the reaction conditions. Here, we report the development of a general Pd-catalysed process for the stereoretentive cross-coupling of secondary alkyl azastannatrane nucleophiles with aryl chlorides, bromides, iodides and triflates. Coupling partners with a wide range of electronic characteristics are well tolerated. The reaction occurs with minimal isomerization of the secondary alkyltin nucleophile, and with retention of absolute configuration. This process constitutes the first general method to use secondary alkyltin reagents in cross-coupling reactions.

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Figure 1: Cross-coupling reactions using configurationally stable, optically active secondary alkyl nucleophiles.
Figure 2: Preparation of alkyl azastannatrane derivatives.
Figure 3: Investigation of the stereorentention of transmetallation.
Figure 4: Pd-catalysed cross-coupling reactions using unactivated, optically active secondary alkyl azastannatrane 12.

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Acknowledgements

The authors acknowledge the National Institutes of Health (5SC2GM096932), the City College of New York (CCNY), the Alfred P. Sloan Foundation and PSC-CUNY for financial support. The authors also acknowledge the National Science Foundation for an instrumentation grant (CHE-0840498). The donors of the American Chemical Society Petroleum Research Fund (50307-DNI1) are thanked for partial support of this research. The authors thank Chunhua Hu for assistance with the X-ray analysis and acknowledge the Molecular Design Institute of NYU for purchase of the single-crystal diffractometer. The authors thank J. Norton for donation of a sample of (–)-sparteine.

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Authors and Affiliations

  1. Department of Chemistry, The City College of New York (CCNY), 160 Convent Avenue, New York, 10031, New York, USA

    Ling Li, Chao-Yuan Wang, Rongcai Huang & Mark R. Biscoe

  2. The Graduate Center of The City University of New York (CUNY), 365 Fifth Avenue, New York, 10016, New York, USA

    Ling Li, Chao-Yuan Wang, Rongcai Huang & Mark R. Biscoe

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L.L. and C-Y.W. performed the experiments and isolated all products. R.H. performed initial exploratory reactions. M.R.B. directed the project and wrote the manuscript.

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Correspondence to Mark R. Biscoe.

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Crystallographic data for compound 11 (CIF 13 kb)

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Li, L., Wang, CY., Huang, R. et al. Stereoretentive Pd-catalysed Stille cross-coupling reactions of secondary alkyl azastannatranes and aryl halides. Nature Chem 5, 607–612 (2013). https://doi.org/10.1038/nchem.1652

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