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. 2018 Oct 3;9(48):8951-8956.
doi: 10.1039/c8sc03606c. eCollection 2018 Dec 28.

Ir(iii)-catalyzed ortho C-H alkylations of (hetero)aromatic aldehydes using alkyl boron reagents

Xiao-Yang Chen  1 , Erik J Sorensen  1
Affiliations

Ir(iii)-catalyzed ortho C-H alkylations of (hetero)aromatic aldehydes using alkyl boron reagents

Xiao-Yang Chen et al. Chem Sci. .

Abstract

Transition-metal-catalyzed C-H alkylation reactions directed by aldehydes or ketones have been largely restricted to electronically activated alkenes. Herein, we report a general protocol for the Ir(iii)-catalyzed ortho C-H alkylations of (hetero)aromatic aldehydes using alkyl boron reagents as the coupling partner. Featuring aniline as an inexpensive catalytic ligand, the method was compatible with a wide variety of benzaldehydes, heterocyclic aldehydes, potassium alkyltrifluoroborates as well as a few α,β-unsaturated aldehydes. An X-ray crystal structure of a benzaldehyde ortho C-H iridation intermediate was also successfully obtained.

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Figures

Scheme 1
Scheme 1. Ir(iii)-catalyzed, site-selective alkylations of (hetero)aromatic and α,β-unsaturated aldehydes using aniline as the catalytic ligand.
Scheme 2
Scheme 2. Scope of substituted benzaldehydes. aThe reactions were performed on a 0.3 mmol scale, and yields are reported as isolated yields. bn-BuBF3K (2 equiv.) and AgF (3 equiv.) were used.
Scheme 3
Scheme 3. Scope of heterocyclic aldehydes. aThe reactions were performed on a 0.3 mmol scale, and yields are reported as isolated yields. bn-BuBF3K (2 equiv.) and AgF (3 equiv.) were used.
Scheme 4
Scheme 4. Scope of potassium alkyltrifluoroborates. aThe reactions were performed on a 0.3 mmol scale, and yields are reported as isolated yields. bDCE (0.1 M) was used as the reaction solvent and the reaction temperature was 80 °C.
Scheme 5
Scheme 5. Isolation and X-ray characterization of iridacycle II and its subsequent transformations. aAll yields are reported as isolated yields.
Scheme 6
Scheme 6. Preliminary studies on the β C–H alkylations of α,β-unsaturated aldehydes. aThe reactions were performed on a 0.3 mmol scale, and yields are reported as isolated yields. bCrotonic acid (30 mol%) was an additive.
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References

    1. Chen X., Engle K. M., Wang D.-H., Yu J.-Q. Angew. Chem., Int. Ed. 2009;48:5094–5115. - PMC - PubMed
    2. Ackermann L. Chem. Commun. 2010;46:4866–4877. - PubMed
    3. Colby D. A., Bergman R. G., Ellman J. A. Chem. Rev. 2010;110:624–655. - PMC - PubMed
    4. Lyons T. W., Sanford M. S. Chem. Rev. 2010;110:1147–1169. - PMC - PubMed
    5. Engle K. M., Mei T.-S., Wasa M., Yu J.-Q. Acc. Chem. Res. 2012;45:788–802. - PMC - PubMed
    6. He J., Wasa M., Chan K. S. L., Shao Q., Yu J.-Q. Chem. Rev. 2017;117:8754–8786. - PMC - PubMed
    1. Gürbüz N., Özdemir I., Çetinkaya B. Tetrahedron Lett. 2005;46:2273–2277.
    2. Padala K., Jeganmohan M. Org. Lett. 2012;14:1134–1137. - PubMed
    3. Lanke V., Ramaiah Prabhu K. Org. Lett. 2013;15:6262–6265. - PubMed
    4. Yang F. Z., Rauch K., Kettelhoit K., Ackermann L. Angew. Chem., Int. Ed. 2014;53:11285–11288. - PubMed
    5. Santhoshkumar R., Mannathan S., Cheng C.-H. J. Am. Chem. Soc. 2015;137:16116–16120. - PubMed
    1. Tremont S. J., Rahman H. U. J. Am. Chem. Soc. 1984;106:5759–5760.
    2. Chen X., Goodhue C. E., Yu J.-Q. J. Am. Chem. Soc. 2006;128:12634–12635. - PubMed
    3. Chen X., Li J.-J., Hao X.-S., Goodhue C. E., Yu J.-Q. J. Am. Chem. Soc. 2006;128:78–79. - PubMed
    4. Ackermann L., Novák P., Vicente R., Hofmann N. Angew. Chem., Int. Ed. 2009;48:6045–6048. - PubMed
    5. Zhang Y.-H., Shi B.-F., Yu J.-Q. Angew. Chem., Int. Ed. 2009;48:6097–6100. - PMC - PubMed
    6. Shabashov D., Daugulis O. J. Am. Chem. Soc. 2010;132:3965–3972. - PMC - PubMed
    7. Chen Q., Ilies L., Nakamura E. J. Am. Chem. Soc. 2011;133:428–429. - PubMed
    8. Zhao Y., Chen G. Org. Lett. 2011;13:4850–4853. - PubMed
    9. Aihara Y., Chatani N. J. Am. Chem. Soc. 2013;135:5308–5311. - PubMed
    10. Chen K., Hu F., Zhang S.-Q., Shi B.-F. Chem. Sci. 2013;4:3906–3911.
    11. Neufeldt S. R., Seigerman C. K., Sanford M. S. Org. Lett. 2013;15:2302–2305. - PMC - PubMed
    12. Thuy-Boun P. S., Villa G., Dang D., Richardson P., Su S., Yu J.-Q. J. Am. Chem. Soc. 2013;135:17508–17513. - PMC - PubMed
    13. Zhang S.-Y., He G., Nack W. A., Zhao Y., Li Q., Chen G. J. Am. Chem. Soc. 2013;135:2124–2127. - PubMed
    14. Zhang S.-Y., Li Q., He G., Nack W. A., Chen G. J. Am. Chem. Soc. 2013;135:12135–12141. - PubMed
    15. Chen K., Shi B.-F. Angew. Chem., Int. Ed. 2014;53:11950–11954. - PubMed
    16. Ilies L., Matsubara T., Ichikawa S., Asako S., Nakamura E. J. Am. Chem. Soc. 2014;136:13126–13129. - PubMed
    17. Zhu R.-Y., He J., Wang X.-C., Yu J.-Q. J. Am. Chem. Soc. 2014;136:13194–13197. - PMC - PubMed
    18. Wang H., Yu S., Qi Z., Li X. Org. Lett. 2015;17:2812–2815. - PubMed
    19. Wippich J., Schnapperelle I., Bach T. Chem. Commun. 2015;51:3166–3168. - PubMed
    20. Zhang S.-Y., Li Q., He G., Nack W. A., Chen G. J. Am. Chem. Soc. 2015;137:531–539. - PubMed
    21. Chen K., Li X., Zhang S.-Q., Shi B.-F. Chem. Commun. 2016;52:1915–1918. - PubMed
    22. Cera G., Haven T., Ackermann L. Angew. Chem., Int. Ed. 2016;55:1484–1488. - PubMed
    23. Peng P., Wang J., Jiang H., Liu H. Org. Lett. 2016;18:5376–5379. - PubMed
    24. Wiest J. M., Pothig A., Bach T. Org. Lett. 2016;18:852–855. - PubMed
    25. Chen Z., Hu L. a., Zeng F., Zhu R., Zheng S., Yu Q., Huang J. Chem. Commun. 2017;53:4258–4261. - PubMed
    26. Shao Q., He J., Wu Q.-F., Yu J.-Q. ACS Catal. 2017;7:7777–7782.
    1. Murai S., Kakiuchi F., Sekine S., Tanaka Y., Kamatani A., Sonoda M., Chatani N. Nature. 1993;366:529–531.
    2. Kakiuchi F., Yamauchi M., Chatani N., Murai S. Chem. Lett. 1996;25:111–112.
    3. Lenges C. P., Brookhart M. J. Am. Chem. Soc. 1999;121:6616–6623.
    4. Jun C.-H., Hong J.-B., Kim Y.-H., Chung K.-Y. Angew. Chem., Int. Ed. 2000;39:3440–3442. - PubMed
    5. Lim Y.-G., Han J.-S., Yang S.-S., Chun J. H. Tetrahedron Lett. 2001;42:4853–4856.
    6. Thalji R. K., Ahrendt K. A., Bergman R. G., Ellman J. A. J. Am. Chem. Soc. 2001;123:9692–9693. - PubMed
    7. Jun C.-H., Moon C. W., Hong J.-B., Lim S.-G., Chung K.-Y., Kim Y.-H. Chem.–Eur. J. 2002;8:485–492. - PubMed
    8. Thalji R. K., Ellman J. A., Bergman R. G. J. Am. Chem. Soc. 2004;126:7192–7193. - PubMed
    9. Martinez R., Chevalier R., Darses S., Genet J.-P. Angew. Chem., Int. Ed. 2006;45:8232–8235. - PubMed
    10. Watzke A., Wilson R. M., O'Malley S. J., Bergman R. G., Ellman J. A. Synlett. 2007;2007:2383–2389.
    11. Tsuchikama K., Kasagawa M., Hashimoto Y.-K., Endo K., Shibata T. J. Organomet. Chem. 2008;693:3939–3942.
    12. Kakiuchi F., Kochi T., Mizushima E., Murai S. J. Am. Chem. Soc. 2010;132:17741–17750. - PubMed
    13. Crisenza G. E. M., McCreanor N. G., Bower J. F. J. Am. Chem. Soc. 2014;136:10258–10261. - PubMed
    14. Kimura N., Kochi T., Kakiuchi F. J. Am. Chem. Soc. 2017;139:14849–14852. - PubMed
    1. Kakiuchi F., Tanaka Y., Sato T., Chatani N., Murai S. Chem. Lett. 1995;24:679–680.
    2. Trost B. M., Imi K., Davies I. W. J. Am. Chem. Soc. 1995;117:5371–5372.
    3. Sato T., Kakiuchi F., Chatani N., Murai S. Chem. Lett. 1998;27:893–894.
    4. Kakiuchi F., Sato T., Igi K., Chatani N., Murai S. Chem. Lett. 2001;30:386–387.
    5. Jun C.-H., Moon C. W., Kim Y.-M., Lee H., Lee J. H. Tetrahedron Lett. 2002;43:4233–4236.
    6. Colby D. A., Bergman R. G., Ellman J. A. J. Am. Chem. Soc. 2006;128:5604–5605. - PMC - PubMed