Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Oct 26;9(3):600-607.
doi: 10.1039/c7sc03149a. eCollection 2018 Jan 21.

Nickel-catalyzed difunctionalization of allyl moieties using organoboronic acids and halides with divergent regioselectivities

Wanfang Li  1 , Jie Kang Boon  1 , Yu Zhao  1
Affiliations

Nickel-catalyzed difunctionalization of allyl moieties using organoboronic acids and halides with divergent regioselectivities

Wanfang Li et al. Chem Sci. .

Abstract

Efficient difunctionalization of alkenes allows the rapid construction of molecular complexity from simple building blocks in organic synthesis. We present herein a nickel-catalyzed dicarbofunctionalization of alkenes using readily available organoboronic acids and organic halides in a three-component fashion. In particular, an unprecedented regioselectivity of the 1,3-dicarbofunctionalization of N-allylpyrimidin-2-amine is achieved when aryl and methyl iodides are utilized. In contrast, the use of alkyl bromides with β-hydrogens results in 1,3-hydroarylation or oxidative 1,3-diarylation. Preliminary mechanistic studies suggest an isomerization involving nickel hydride in the 1,3-difunctionalization reactions. On the other hand, the use of alkenyl or alkynyl halides promotes alternative regioselectivities to deliver 1,2-alkenylcarbonation or intriguing 2,1-alkynylcarbonation products. Such 2,1-alkynylarylation is also applicable to N-allylbenzamide as a different class of substrates. Overall, this nickel-catalyzed process proves to be powerful in delivering versatile difunctionalized compounds using readily available reagents/catalysts and a simple procedure.

PubMed Disclaimer

Figures

Scheme 1
Scheme 1. TM-catalyzed difunctionalization of alkenes.
Scheme 2
Scheme 2. Scope of 1,3-diarylation/arylalkenylation.
Scheme 3
Scheme 3. Mechanistic investigations.
Scheme 4
Scheme 4. Plausible mechanism for the 1,3-dicarbofunctionalization.
Scheme 5
Scheme 5. Scope of 1,2-alkenylcarbonation.
Scheme 6
Scheme 6. Proposed mechanism of 1,2-alkenyl carbonalization.
Scheme 7
Scheme 7. 2,1-Alkynylcarbonation. aReaction in toluene. bReactions in toluene with PCy3. cReactions in dioxane with dppm.
Scheme 8
Scheme 8. Proposed mechanism for alkynylarylation.
Scheme 9
Scheme 9. Difunctionalization using alkyl halides.
Scheme 10
Scheme 10. 1,3- and 1,4-hydrocarbonation using alkyl halides bearing β-hydrogen.
Scheme 11
Scheme 11. Synthesis of various aminopyrimidine pharmacophores.
See this image and copyright information in PMC

References

    1. For selected Pd-catalyzed alkene dicarbofunctionalization, see:

    2. Catellani M., Chiusoli G. P., Concari S. Tetrahedron. 1989;45:5263–5268.
    3. Shaulis K. M., Hoskin B. L., Townsend J. R., Goodson F. E., Incarvito C. D., Rheingold A. L. J. Org. Chem. 2002;67:5860–5863. - PubMed
    4. Liao L., Jana R., Urkalan K. B., Sigman M. S. J. Am. Chem. Soc. 2011;133:5784–5787. - PMC - PubMed
    5. Stokes B. J., Liao L., de Andrade A. M., Wang Q., Sigman M. S. Org. Lett. 2014;16:4666–4669. - PMC - PubMed
    6. Wang D.-C., Niu H.-Y., Xie M.-S., Qu G.-R., Wang H.-X., Guo H.-M. Org. Lett. 2014;16:262–265. - PubMed
    7. Wu X., Lin H.-C., Li M.-L., Li L.-L., Han Z.-Y., Gong L.-Z. J. Am. Chem. Soc. 2015;137:13476–13479. - PubMed
    8. Liu Z., Zeng T., Yang K. S., Engle K. M. J. Am. Chem. Soc. 2016;138:15122–15125. - PubMed
    9. Yang K. S., Gurak J. A., Liu Z., Engle K. M. J. Am. Chem. Soc. 2016;138:14705–14712. - PubMed
    10. Yin G., Mu X., Liu G. Acc. Chem. Res. 2016;49:2413–2423. - PubMed

    1. For selected recent Cu-catalyzed alkene dicarbofunctionalization, see:

    2. You W., Brown M. K. J. Am. Chem. Soc. 2014;136:14730–14733. - PubMed
    3. You W., Brown M. K. J. Am. Chem. Soc. 2015;137:14578–14581. - PubMed
    4. Thapa S., Basnet P., Giri R. J. Am. Chem. Soc. 2017;139:5700–5703. - PubMed
    5. Wu L., Wang F., Wan X., Wang D., Chen P., Liu G. J. Am. Chem. Soc. 2017;139:2904–2907. - PubMed

    1. For selected recent Ni-catalyzed alkene dicarbofunctionalization, see:

    2. Qin T., Cornella J., Li C., Malins L. R., Edwards J. T., Kawamura S., Maxwell B. D., Eastgate M. D., Baran P. S. Science. 2016;352:801–805. - PMC - PubMed
    3. Xiao Y. L., Min Q. Q., Xu C., Wang R. W., Zhang X. G. Angew. Chem., Int. Ed. 2016;55:5837–5841. - PubMed
    4. Derosa J., Tran V., Boulous M. N., Chen J. S., Engle K. M. J. Am. Chem. Soc. 2017;139:10657–10660. - PubMed
    5. Shrestha B., Basnet P., Dhungana R. K., Kc S., Thapa S., Sears J. M., Giri R. J. Am. Chem. Soc. 2017;139:10653–10656. - PubMed
    1. Stüdemann T., Knochel P. Angew. Chem., Int. Ed. 1997;36:93–95.
    2. Nakao Y., Yukawa T., Hirata Y., Oda S., Satoh J., Hiyama T. J. Am. Chem. Soc. 2006;128:7116–7117. - PubMed
    3. Nakao Y., Yada A., Ebata S., Hiyama T. J. Am. Chem. Soc. 2007;129:2428–2429. - PubMed
    4. Terao J., Bando F., Kambe N. Chem. Commun. 2009;2009:7336–7338. - PubMed
    5. Hirata Y., Yada A., Morita E., Nakao Y., Hiyama T., Ohashi M., Ogoshi S. J. Am. Chem. Soc. 2010;132:10070–10077. - PubMed
    6. Minami Y., Yoshiyasu H., Nakao Y., Hiyama T. Angew. Chem., Int. Ed. 2013;52:883–887. - PubMed
    7. Hoshimoto Y., Ohata T., Sasaoka Y., Ohashi M., Ogoshi S. J. Am. Chem. Soc. 2014;136:15877–15880. - PubMed
    8. Nakai K., Yoshida Y., Kurahashi T., Matsubara S. J. Am. Chem. Soc. 2014;136:7797–7800. - PubMed
    9. Xue F., Zhao J., Hor T. S. A., Hayashi T. J. Am. Chem. Soc. 2015;137:3189–3192. - PubMed
    10. Wang X., Nakajima M., Serrano E., Martin R. J. Am. Chem. Soc. 2016;138:15531–15534. - PubMed
    1. Monks B. M., Cook S. P. J. Am. Chem. Soc. 2012;134:15297–15300. - PubMed
    2. Li Z., García-Domínguez A., Nevado C. J. Am. Chem. Soc. 2015;137:11610–11613. - PubMed
    3. Li Z., García-Domínguez A., Nevado C. Angew. Chem., Int. Ed. 2016;55:6938–6941. - PubMed