Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

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.

References

  1. De Meijere, A. & Diederich, F. (eds) Metal-Catalysed Cross-Coupling Reactions (Wiley-VCH, 2004).

    Book  Google Scholar 

  2. Netherton, M. R. & Fu, G. C. in Topics in Organometallic Chemistry: Palladium in Organic Synthesis (ed. Tsuji, J.) 85–108 (Springer, 2005).

    Book  Google Scholar 

  3. Rudolph, A. & Lautens, M. Secondary alkyl halides in transition metal-catalyzed cross-coupling reactions. Angew. Chem. Int. Ed. 48, 2656–2670 (2009).

    Article  CAS  Google Scholar 

  4. Chemler, S. R., Trauner, D. & Danishefsky, S. J. The β-alkyl Suzuki–Miyaura cross-coupling reaction: development, mechanistic study, and applications in natural product synthesis. Angew. Chem. Int. Ed. 40, 4544–4568 (2001).

    Article  CAS  Google Scholar 

  5. Luo, X. et al. Superior effect of a π-acceptor ligand (phosphine-electron-deficient olefin ligand) in the Negishi coupling involving alkylzinc reagents. Org. Lett. 9, 4571–4574 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Dreher, S. D., Dormer, P. G., Sandrock, D. L. & Molander, G. A. Efficient cross-coupling of secondary alkyltrifluoroborates with aryl chlorides—reaction discovery using parallel microscale experimentation. J. Am. Chem. Soc. 130, 9257–9259 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Han, C. & Buchwald, S. L. Negishi coupling of secondary alkylzinc halides with aryl bromides and chlorides. J. Am. Chem. Soc. 131, 7532–7533 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nakao, Y., Takeda, M., Matsumoto, T. & Hiyama, T. Cross-coupling reactions through the intramolecular activation of alkyl(triorgano)silanes. Angew. Chem. Int. Ed. 45, 4447–4450 (2010).

    Article  CAS  Google Scholar 

  9. Calimsiz, S. & Organ, M. G. Negishi cross-coupling of secondary alkylzinc halides with aryl/heteroaryl halides using Pd–PEPPSI–IPent. Chem. Commun. 47, 5181–5183 (2011).

    Article  CAS  Google Scholar 

  10. Joshi-Pangu, A., Ganesh, M. & Biscoe, M. R. Nickel-catalyzed Negishi cross-coupling reactions of secondary alkylzinc halides and aryl iodides. Org. Lett. 13, 1218–1221 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Joshi-Pangu, A., Wang, C-Y. & Biscoe, M. R. Nickel-catalyzed Kumada cross-coupling reactions of tertiary alkylmagnesium halides and aryl bromides/triflates. J. Am Chem. Soc. 133, 8478–8481 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Joshi-Pangu, A. & Biscoe, M. R. The use of tertiary alkyl nucleophiles in metal-catalyzed cross-coupling reactions. Synlett 23, 1103–1107 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Joshi-Pangu, A. et al. Palladium-catalyzed borylation of primary alkyl bromides. J. Org. Chem. 77, 6629–6633 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Boudier, A., Bromm, L. O., Lotz, M. & Knochel, P. New applications of polyfunctional organometallic compounds in organic synthesis. Angew. Chem. Int. Ed. 39, 4414–4435 (2000).

    Article  Google Scholar 

  15. Hoffman, R. W., Hölzer, B., Knopff, O. & Harms, K. Asymmetric synthesis of a chiral secondary Grignard reagent. Angew. Chem. Int. Ed. 39, 3072–3074 (2000).

    Article  Google Scholar 

  16. Hölzer, B. & Hoffman, R. W. Kumada–Corriu coupling of Grignard reagents, probed with a chiral Grignard reagent. Chem. Commun. 732–733 (2003).

  17. Boudier, A., Darcel, C., Flachsman, F., Micouin, L., Oestreich, M. & Knochel, P. Stereoselective preparation and reactions of configurationally defined dialkylzinc compounds. Chem. Eur. J. 6, 2748–2761 (2000).

    Article  CAS  PubMed  Google Scholar 

  18. Campos, K. R., Klapars, A., Waldman, J. H., Dormer, P. G. & Chen, C-Y. Enantioselective, palladium-catalyzed α-arylation of N-boc-pyrrolidine. J. Am. Chem. Soc. 128, 3538–3539 (2006).

    Article  CAS  PubMed  Google Scholar 

  19. Thaler, T. et al. Highly diastereoselective Csp3–Csp2 Negishi cross-coupling with 1,2-, 1,3- and 1,4-substituted cycloalkylzinc compound. Nature Chem. 2, 125–130 (2010).

    Article  CAS  Google Scholar 

  20. Denmark, S. E. & Werner, N. S. On the stereochemical course of palladium-catalyzed cross-coupling of allylic silanolate salts with aromatic bromides. J. Am. Chem. Soc. 132, 3612–3620 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ridgway, B. H. & Woerpel, K. A. Transmetalation of alkylboranes to palladium in the Suzuki coupling reaction proceeds with retention of stereochemistry. J. Org. Chem. 63, 458–460 (1998).

    Article  CAS  PubMed  Google Scholar 

  22. Imao, D., Glasspoole, B. W., Laberge, V. S. & Crudden, C. M. Cross coupling reactions of chiral secondary organoboronic esters with retention of configuration. J. Am. Chem. Soc. 131, 5024–5025 (2009).

    Article  CAS  PubMed  Google Scholar 

  23. Kells, K. W. & Chong, J. M. Stille coupling of stereochemically defined α-sulfonamidoorganostannanes. J. Am. Chem. Soc. 126, 15666–15667 (2004).

    Article  CAS  PubMed  Google Scholar 

  24. Ye, J., Bhatt, R. K. & Falck, J. R. Stereospecifc palladium/copper cocatalyzed cross-coupling of α-alkoxy- and α-aminostannanes with acyl chlorides. J. Am. Chem. Soc. 116, 1–5 (1994).

    Article  CAS  Google Scholar 

  25. Falck, J. R., Bhatt, R. K. & Ye, J. Tin–copper transmetalation: cross-coupling of α-heteroatom-substituted alkyltributylstannanes with organohalides. J. Am. Chem. Soc. 117, 5973–5982 (1995).

    Article  CAS  Google Scholar 

  26. Mohapatra, S., Bandyopadhyay, A., Barma, D. K., Capdevila, J. H. & Falck, J. R. Chiral α, β-dialkoxy- and α-alkoxy-β-aminostannanes: preparation and copper-mediated cross-coupling. Org. Lett. 5, 4759–4762 (2003).

    Article  CAS  PubMed  Google Scholar 

  27. Falck, J. R., Patel, P. K. & Bandyopadhyay, A. Stereospecific cross-coupling of α-(thiocarbamoyl)organostannanes with alkenyl, aryl, and heteroaryl iodides. J. Am. Chem. Soc. 129, 790–793 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Goli, M., He, A. & Falck, J. R. Pd-catalyzed cross-coupling of alpha-(acyloxy)-tri-n-butylstannanes with alkenyl, aryl, and heteroaryl electrophiles. Org. Lett. 13, 344–346 (2011).

    Article  CAS  PubMed  Google Scholar 

  29. Kalkofen, R. & Hoppe, D. First example of an enantiospecific sp3sp2 Stille coupling of a chiral allylstannane with aryl halides. Synlett 2006, 1959–1961 (2006).

    Article  CAS  Google Scholar 

  30. Lange, H., Fröhlich, R. & Hoppe, D. Cu(I)-catalyzed stereospecific coupling reactions of enantioenriched α-stannylated benzyl carbamates and their application. Tetrahedron 64, 9123–9135 (2008).

    Article  CAS  Google Scholar 

  31. Sandrock, D. L., Jean-Gerard, L., Chen, C-Y., Dreher, S. D. & Molander, G. A. Stereospecific cross-coupling of secondary alkyl β-trifluoroboraroamides. J. Am. Chem. Soc. 132, 17108–17110 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ohmura, T., Awano, T. & Suginome, M. Stereospecific Suzuki–Miyaura coupling of chiral α-(acylamino)benzylboronic esters with inversion of configuration. J. Am. Chem. Soc. 132, 13191–13193 (2010).

    Article  CAS  PubMed  Google Scholar 

  33. Daini, M. & Suginome, M. Palladium-catalyzed, stereoselective, cyclizative alkenylboration of carbon–carbon double bonds through activation of a boron–chlorine bond. J. Am. Chem. Soc. 133, 4758–4761 (2011).

    Article  CAS  PubMed  Google Scholar 

  34. Awano, T., Ohmura, T. & Suginome, M. Inversion or retention? Effects of acidic additives on the stereochemical course in enantiospecific Suzuki–Miyaura coupling of α-(acetylamino)benzylboronic esters. J. Am. Chem. Soc. 133, 20738–20741 (2011).

    Article  CAS  PubMed  Google Scholar 

  35. Lee, J. C. H., McDonald, R. & Hall, D. G. Enantioselective preparation and chemoselective cross-coupling of 1,1-diboron compounds. Nature Chem. 3, 894–899 (2011).

    Article  CAS  Google Scholar 

  36. Partridge, B. M., Chausset-Boissarie, L., Burns, M., Pulis, A. P. & Aggarwal, V. K. Enantioselective synthesis and cross-coupling of tertiary propargylic boronic esters using lithiation–borylation of propargylalic carbamates. Angew. Chem. Int. Ed. 51, 11795–11799 (2012).

    Article  CAS  Google Scholar 

  37. Molander, G. A. & Wisniewski, S. R. Stereospecific cross-coupling of secondary organotrifluoroborates: potassium 1-(benzyloxy)alkyltrifluoroborates. J. Am. Chem. Soc. 134, 16856–16868 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Itami, K., Kamei, T. & Yoshida, J. Unusually accelerated silylmethyl transfer from tin in Stille coupling: implication of coordination-driven transmetalation J. Am. Chem. Soc. 123, 8773–8779 (2001).

    Article  CAS  PubMed  Google Scholar 

  39. Littke, A. F. & Fu, G. C. The first general method for Stille cross-coupling of aryl chlorides. Angew. Chem. Int. Ed. 38, 2411–2413 (1999).

    Article  CAS  Google Scholar 

  40. Labadie, J. W. & Stille, J. K. Mechanisms of the palladium-catalyzed couplings of acid chlorides with organotin reagents. J. Am. Chem. Soc. 105, 6129–6137 (1983).

    Article  CAS  Google Scholar 

  41. Vedejs, E., Haight, A. R. & Moss, W. O. Internal coordination at tin promotes selective alkyl transfer in the Stille coupling reaction. J. Am. Chem. Soc. 114, 6556–6558 (1992).

    Article  CAS  Google Scholar 

  42. Jensen, M. S. et al. Anti-methicillin-resistant Staphylococcus aureus (MRSA) carbapenem via stannatrane-mediated Stille coupling. Org. Lett. 2, 1081–1084 (2000).

    Article  CAS  PubMed  Google Scholar 

  43. Sebehar, H. L., Yoshida, K. & Hegedus, L. S. Effect of adjacent chiral tertiary and quaternary centers on the metal-catalyzed allylic substitution reaction. J. Org. Chem. 67, 3788–3795 (2002).

    Article  CAS  Google Scholar 

  44. Hicks, J. D., Hyde, A. M., Cuezva, A. M. & Buchwald, S. L. Pd-catalyzed N-arylation of secondary acyclic amides: catalyst development, scope, and computational study. J. Am. Chem. Soc. 131, 16720–16734 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Mee, S. P. H., Lee, V. & Baldwin, J. E. Stille coupling made easier—the synergistic effect of copper(I) salts and the fluoride ion. Angew. Chem. Int. Ed. 43, 1132–1136 (2004).

    Article  CAS  Google Scholar 

  46. Beak, P., Kerrick, S. T., Wu, S. & Chu, J. Complex induced proximity effects: enantioselective syntheses based on asymmetric deprotonations of N-boc-pyrrolidines. J. Am. Chem. Soc. 116, 3231–3239 (1994).

    Article  CAS  Google Scholar 

  47. Beak, P., Basu, A., Gallagher, D. J., Park, Y. S. & Thayumanavan, S. Regioselective, diastereoselective, and enantioselective lithiation–substitution sequences: reaction pathways and synthetic applications. Acc. Chem. Res. 29, 552–560 (1996).

    Article  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

Contributions

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.

Corresponding author

Correspondence to Mark R. Biscoe.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 3746 kb)

Supplementary information

Crystallographic data for compound 11 (CIF 13 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchem.1652

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing