Transition-Metal-Free Controllable Single and Double Difluoromethylene Formal Insertions into C−H Bonds of Aldehydes with TMSCF2Br
An Liu
Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai, 200032 China
Search for more papers by this authorProf. Dr. Chuanfa Ni
Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai, 200032 China
Search for more papers by this authorDr. Qiqiang Xie
Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai, 200032 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Jinbo Hu
Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai, 200032 China
Search for more papers by this authorAn Liu
Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai, 200032 China
Search for more papers by this authorProf. Dr. Chuanfa Ni
Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai, 200032 China
Search for more papers by this authorDr. Qiqiang Xie
Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai, 200032 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Jinbo Hu
Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai, 200032 China
Search for more papers by this authorAbstract
We have developed a new strategy for controllable single and double difluoromethylene (CF2) formal insertions into C−H bonds of aldehydes with nearly full selectivity under transition-metal-free conditions. The key to the success of controllable CF2 insertions lies in the well-defined formation of 2,2-difluoroenolsilyl ether and 2,2,3,3-tetrafluorocyclopropanolsilyl ether intermediates using difluorocarbene reagent TMSCF2Br (TMS=trimethylsilyl). These two intermediates can react with various electrophiles including proton sources and various halogenation reagents, allowing for the access to diverse arrays of ketones containing difluoromethylene (CF2) and tetrafluoroethylene (CF2CF2) units. The first synthesis of relatively stable 2,2,3,3-tetrafluorocyclopropanolsilyl ethers has been achieved, which offers a new platform to explore other unknown chemical space.
Conflict of interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
Supporting Information
As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
| Filename | Description |
|---|---|
| ange202217088-sup-0001-misc_information.pdf14.9 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1
- 1aY. Zhou, J. Wang, Z. Gu, S. Wang, W. Zhu, J. L. Acena, V. A. Soloshonok, K. Izawa, H. Liu, Chem. Rev. 2016, 116, 422;
- 1bM. Inoue, Y. Sumii, N. Shibata, ACS Omega 2020, 5, 10633;
- 1cB. M. Johnson, Y.-Z. Shu, X. Zhuo, N. A. Meanwell, J. Med. Chem. 2020, 63, 6315;
- 1dY. Ogawa, E. Tokunaga, O. Kobayashi, K. Hirai, N. Shibata, iScience 2020, 23, 101467;
- 1eR. Britton, V. Gouverneur, J.-H. Lin, M. Meanwell, C. Ni, G. Pupo, J.-C. Xiao, J. Hu, Nat. Rev. Methods Primers 2021, 1, 47.
- 2
- 2aN. A. Meanwell, J. Med. Chem. 2018, 61, 5822.
- 3
- 3aM. Hird, Chem. Soc. Rev. 2007, 36, 2070;
- 3bP. Kirsch, J. Fluorine Chem. 2015, 177, 29.
- 4
- 4aJ. B. I. Sap, C. F. Meyer, N. J. W. Straathof, N. Iwumene, C. W. am Ende, A. A. Trabanco, V. Gouverneur, Chem. Soc. Rev. 2021, 50, 8214;
- 4bY. Zafrani, S. Saphier, E. Gershonov, Future Med. Chem. 2020, 12, 361;
- 4cC. D. Sessler, M. Rahm, S. Becker, J. M. Goldberg, F. Wang, S. J. Lippard, J. Am. Chem. Soc. 2017, 139, 9325.
- 5
- 5aX. Wang, S. Pan, Q. Luo, Q. Wang, C. Ni, J. Hu, J. Am. Chem. Soc. 2022, 144, 12202;
- 5bB. Trang, Y. Li, X.-S. Xue, M. Ateia, K. N. Houk, W. R. Dichtel, Science 2022, 377, 839;
- 5cA. S. Tsyrulnikova, S. V. Vershilov, L. M. Popova, N. V. Lebedev, E. V. Litvinenko, N. G. Ismagilov, J. Fluorine Chem. 2022, 257–258, 109972.
- 6M. G. Evich, M. J. B. Davis, J. P. McCord, B. Acrey, J. A. Awkerman, D. R. U. Knappe, A. B. Lindstrom, T. F. Speth, C. Tebes-Stevens, M. J. Strynar, Z. Wang, E. J. Weber, W. M. Henderson, J. W. Washington, Science 2022, 375, eabg9065.
- 7For selected reviews for the synthesis of compounds containing CF2 unit, see:
- 7aM. J. Tozer, T. F. Herpin, Tetrahedron 1996, 52, 8619;
- 7bG. Pattison, Eur. J. Org. Chem. 2018, 3520;
- 7cS. Sadhukhan, J. Santhi, B. Baire, Chem. Eur. J. 2020, 26, 7145.
- 8For selected reviews for the synthesis of compounds containing CF2CF2 unit, see:
- 8aJ. Václavík, I. Klimánková, A. Budinská, P. Beier, Eur. J. Org. Chem. 2018, 3554;
- 8bV. G. Nenajdenko, V. M. Muzalevskiy, A. V. Shastin, Chem. Rev. 2015, 115, 973.
- 9For selected reviews, see:
- 9aD. L. Brahms, W. P. Dailey, Chem. Rev. 1996, 96, 1585;
- 9bJ. Hu, C. Ni, Synthesis 2014, 46, 842;
- 9cA. D. Dilman, V. V. Levin, Acc. Chem. Res. 2018, 51, 1272;
- 9dW. Zhang, Y. Wang, Tetrahedron Lett. 2018, 59, 1301;
- 9eX. Wang, X. Wang, J. Wang, Tetrahedron 2019, 75, 949;
- 9fJ.-H. Lin, J.-C. Xiao, Acc. Chem. Res. 2020, 53, 1498;
- 9gW. Zhou, W.-J. Pan, J. Chen, M. Zhang, J.-H. Lin, W. Cao, J.-C. Xiao, Chem. Commun. 2021, 57, 9316.
- 10For selected examples observing uncontrollable byproducts, see:
- 10aY. Kobayashi, I. Kumadaki, J. Chem. Soc. Perkin Trans. 1 1980, 661;
- 10bD. M. Wiemers, D. J. Burton, J. Am. Chem. Soc. 1986, 108, 832;
- 10cD.-B. Su, J.-X. Duan, A.-J. Yu, Q.-Y. Chen, J. Fluorine Chem. 1993, 65, 11;
- 10dM. M. Kremlev, W. Tyrra, A. I. Mushta, D. Naumann, Y. L. Yagupolskii, J. Fluorine Chem. 2010, 131, 212;
- 10eZ. Feng, Q.-Q. Min, X.-P. Fu, L. An, X. Zhang, Nat. Chem. 2017, 9, 918.
- 11For examples achieving sequential CF2 insertions, see:
- 11aZ.-Y. Yang, D. M. Wiemers, D. J. Burton, J. Am. Chem. Soc. 1992, 114, 4402;
- 11bZ.-Y. Yang, D. J. Burton, J. Fluorine Chem. 2000, 102, 89;
- 11cQ. Xie, Z. Zhu, L. Li, C. Ni, J. Hu, Chem. Sci. 2020, 11, 276;
- 11dRef. 5a.
- 12For representative examples achieving single CF2 insertion, see:
- 12aV. V. Levin, A. A. Zemtsov, M. I. Struchkova, A. D. Dilman, Org. Lett. 2013, 15, 917;
- 12bM. C. Leclerc, J. M. Bayne, G. M. Lee, S. I. Gorelsky, M. Vasiliu, I. Korobkov, D. J. Harrison, D. A. Dixon, R. T. Baker, J. Am. Chem. Soc. 2015, 137, 16064;
- 12cM. D. Levin, T. Q. Chen, M. E. Neubig, C. M. Hong, C. A. Theulier, I. J. Kobylianskii, M. Janabi, J. P. O'Neil, F. D. Toste, Science 2017, 356, 1272;
- 12dQ. Xie, L. Li, Z. Zhu, R. Zhang, C. Ni, J. Hu, Angew. Chem. Int. Ed. 2018, 57, 13211; Angew. Chem. 2018, 130, 13395;
- 12eX.-P. Fu, X.-S. Xue, X.-Y. Zhang, Y.-L. Xiao, S. Zhang, Y.-L. Guo, X. Leng, K. N. Houk, X. Zhang, Nat. Chem. 2019, 11, 948;
- 12fJ. Mestre, S. Castillon, O. Boutureira, J. Org. Chem. 2019, 84, 15087;
- 12gZ.-W. Xu, W. Zhang, J.-H. Lin, C.-M. Jin, J.-C. Xiao, Chin. J. Chem. 2020, 38, 1647;
- 12hM. M. Wade Wolfe, J. P. Shanahan, J. W. Kampf, N. K. Szymczak, J. Am. Chem. Soc. 2020, 142, 18698;
- 12iS. Pan, Q. Xie, X. Wang, Q. Wang, C. Ni, J. Hu, Chem. Commun. 2022, 58, 5156.
- 13
- 13aA. Liu, C. Ni, Q. Xie, J. Hu, Angew. Chem. Int. Ed. 2022, 61, e202115467; Angew. Chem. 2022, 134, e202115467;
- 13bJ. Y. Chai, H. Cha, H. B. Kim, D. Y. Chi, Tetrahedron 2020, 76, 131370.
- 14
- 14aM. Decostanzi, J. M. Campagne, E. Leclerc, Org. Biomol. Chem. 2015, 13, 7351;
- 14bX.-S. Hu, J.-S. Yu, J. Zhou, Chem. Commun. 2019, 55, 13638.
- 15T. R. McDonald, L. R. Mills, M. S. West, S. A. L. Rousseaux, Chem. Rev. 2021, 121, 3.
- 16For selected examples, see:
- 16aX. Zhang, X. Zhang, Q. Song, P. Sivaguru, Z. Wang, G. Zanoni, X. Bi, Angew. Chem. Int. Ed. 2022, 61, e202116190; Angew. Chem. 2022, 134, e202116190;
- 16bJ. R. Box, A. P. Atkins, A. J. J. Lennox, Chem. Sci. 2021, 12, 10252;
- 16cM. Miele, A. Citarella, N. Micale, W. Holzer, V. Pace, Org. Lett. 2019, 21, 8261;
- 16dY. Duan, J.-H. Lin, J.-C. Xiao, Y.-C. Gu, Org. Chem. Front. 2017, 4, 1917.
- 17For selected examples, see:
- 17aP. Crabbe, A. Cervantes, A. Cruz, E. Galeazzi, J. Iriarte, E. Velarde, J. Am. Chem. Soc. 1973, 95, 6655;
- 17bH. Amii, Y. Kageshima, C. Suzuki, K. Oshiro, Synlett 2015, 26, 63;
- 17cM. Hu, C. Ni, L. Li, Y. Han, J. Hu, J. Am. Chem. Soc. 2015, 137, 14496;
- 17dX. Song, J. Chang, D. Zhu, J. Li, C. Xu, Q. Liu, M. Wang, Org. Lett. 2015, 17, 1712;
- 17eT. Aono, H. Sasagawa, K. Fuchibe, J. Ichikawa, Org. Lett. 2015, 17, 5736;
- 17fM. D. Kosobokov, V. V. Levin, M. I. Struchkova, A. D. Dilman, Org. Lett. 2015, 17, 760;
- 17gX. Song, S. Tian, Z. Zhao, D. Zhu, M. Wang, Org. Lett. 2016, 18, 3414;
- 17hK. Fuchibe, T. Aono, J. Hu, J. Ichikawa, Org. Lett. 2016, 18, 4502;
- 17iR. Liu, J. Hu, Org. Lett. 2022, 24, 3589.
- 18S. Kobayashi, Y. Yamamoto, H. Amii, K. Uneyama, Chem. Lett. 2000, 29, 1366.
- 19
- 19aW. R. Dolbier, M. A. Battiste, Chem. Rev. 2003, 103, 1071;
- 19bK. S. Adekenova, P. B. Wyatt, S. M. Adekenov, Beilstein J. Org. Chem. 2021, 17, 245.
- 20Unlike our relatively stable compounds 4, their analogous [(1-ethoxy-2,2,3,3-tetrafluorocyclopropoxy)trimethylsilane] was previously found to be too unstable to be characterized by NMR. see: O. V. Fedorov, M. I. Struchkova, A. D. Dilman, J. Org. Chem. 2016, 81, 9455.
- 21For selected examples by our group, see:
- 21aF. Wang, W. Zhang, J. Zhu, H. Li, K.-W. Huang, J. Hu, Chem. Commun. 2011, 47, 2411;
- 21bL. Li, F. Wang, C. Ni, J. Hu, Angew. Chem. Int. Ed. 2013, 52, 12390; Angew. Chem. 2013, 125, 12616;
- 21cQ. Xie, C. Ni, R. Zhang, L. Li, J. Rong, J. Hu, Angew. Chem. Int. Ed. 2017, 56, 3206; Angew. Chem. 2017, 129, 3254;
- 21dQ. Xie, Z. Zhu, L. Li, C. Ni, J. Hu, Angew. Chem. Int. Ed. 2019, 58, 6405; Angew. Chem. 2019, 131, 6471;
- 21eQ. Xie, Z. Zhu, C. Ni, J. Hu, Org. Lett. 2019, 21, 9138;
- 21fR. Zhang, Q. Li, Q. Xie, C. Ni, J. Hu, Chem. Eur. J. 2021, 27, 17773;
- 21gRef. 13;
- 21hRef. 17i;
- 21iRef. 5a.
- 22For recent examples by other groups, see:
- 22aH. Hayashi, H. Takano, H. Katsuyama, Y. Harabuchi, S. Maeda, T. Mita, Chem. Eur. J. 2021, 27, 10040;
- 22bY. Jia, Y. Yuan, J. Huang, Z.-X. Jiang, Z. Yang, Org. Lett. 2021, 23, 2670;
- 22cH. Lim, S. Seong, Y. Kim, S. Seo, S. Han, J. Am. Chem. Soc. 2021, 143, 19966;
- 22dA. L. Trifonov, A. D. Dilman, Org. Lett. 2021, 23, 6977;
- 22eY. Wang, S. Wang, P. Qiu, L. Fang, K. Wang, Y. Zhang, C. Zhang, T. Zhao, Org. Biomol. Chem. 2021, 19, 4788;
- 22fY. Wang, S. Wang, C. Zhang, T. Zhao, Y. Hu, M. Zhang, P. Chen, Y. Fu, Synlett 2021, 32, 1123;
- 22gR.-Y. Yang, H. Wang, B. Xu, Chem. Commun. 2021, 57, 4831;
- 22hZ. Zhu, V. Krishnamurti, X. Ispizua-Rodriguez, C. Barrett, G. K. S. Prakash, Org. Lett. 2021, 23, 6494.
- 23G. K. S. Prakash, J. Hu, G. A. Olah, J. Fluorine Chem. 2001, 112, 357.
This is the
German version
of Angewandte Chemie.
Note for articles published since 1962:
Do not cite this version alone.
Take me to the International Edition version with citable page numbers, DOI, and citation export.
We apologize for the inconvenience.
