Cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides

Li, Chao; Cao, Yi-Xuan; Wang, Rui; Wang, Yi-Ning; Lan, Quan; Wang, **-Sheng

doi:10.1038/s41467-018-07525-y

Cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides

Article
Open access
Published: 23 November 2018

Volume 9, article number 4951, (2018)
Cite this article

Download PDF

You have full access to this open access article

From

View current issue

Cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides

Download PDF

6669 Accesses
35 Citations
1 Altmetric
Explore all metrics

Abstract

The selective incorporation of gem-difluoroalkyl groups into biologically active molecules has long been used as an efficient strategy for drug design and discovery. However, the catalytic C(sp³)-CF₂ bond-forming cross-coupling reaction for selective incorporation of difluoromethylene group into diverse alkyl chains, especially more sterically demanding secondary and tertiary functionalized alkanes, still remains as a major challenge. Herein, we describe a cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides, which exhibited high efficiency, broad scope and mild conditions. The synthetic utility of this method is demonstrated by late-stage difluoroalkylation of donepezil, a well-known acetylcholinesterase inhibitor used to treat the Alzheimer’s disease. Preliminary mechanistic investigations indicate that a difluoroalkyl radical is involved in a Co(I)/Co(III) catalytic cycle. This cobalt-catalyzed fluoroalkylation thus offers insights into an efficient way for the synthesis of fluoroalkylated bioactive molecules for drug discovery.

Organozinc pivalates for cobalt-catalyzed difluoroalkylarylation of alkenes

Article Open access 16 July 2021

α-Fluorination of carbonyls with nucleophilic fluorine

Article 04 March 2019

Copper-catalysed difluorocarbene transfer enables modular synthesis

Article 12 June 2023

Introduction

The wide use of fluorinated compounds in pharmaceuticals, agrochemicals, and advanced materials vigorously propelled the development of efficient methods for the incorporation of fluorine or fluorinated moieties into organic molecules^1,2,3. In the past decades, transition-metal-catalyzed fluoroalkylation has emerged as an efficient and convenient alternative approach to direct fluorination for facile synthesis of fluorine-containing organic compounds^{4,Full size image}

Based on all of these results and the previous reports^64,65,66, a proposed mechanism of Co(I) initiated cross-coupling was described in Fig. 5. First of all, reduction of Co(II) by zinc metal afforded the catalytically active Co(I) species A to start the cycle⁶⁶. Transmetallation between Co(I) A and enol anion B, which was in situ generated with the assistance of LDA, afforded the corresponding Co(I) complex C and D. A single electron oxidation of Co(I) C by fluoroalkylating reagent 2 generated the corresponding radical and Co(II) species, which was further transformed to Co(III) intermediate F after the following radical oxidation. At last, the reductive elimination of F furnished the final product 3 and regenerated Co(I) species to enter the next catalytic circle.

Discussion

In summary, we have developed a difluoroalkylation of tertiary C–H bonds through cobalt-catalyzed cross-coupling between aryl ketones and fluoroalkyl bromides. Mechanistic investigations indicated this C–H fluoroalkylation proceeds via a Co(I)/Co(III) catalytic cycle involving an in situ generated difluoroalkyl radical. This method has demonstrated mild conditions, broad substrate scope, and thus enabled the late-stage difluoroalkylation of complex molecules. This strategy will offer a solution for facile synthesis of quaternary alkyl difluorides. Further application of this method to fluorine-containing modification of complex biologically active molecules is still underway in our laboratory.

Methods

General procedure for the cobalt-catalyzed cross-coupling

To a 50 mL of Schlenk tube was added aryl ketone 1 (1.0 equiv, 0.2 mmol), CoBr₂ (10 mol %, 0.02 mmol) and dppBz (10 mol %, 0.02 mmol) under air, followed by Zn (0.5 equiv, 0.1 mmol). The mixture was evacuated and backfilled with N₂ (three times). THF (2 mL) was added then followed by LDA (105 mol%, 0.21 mmol) subsequently. The Schlenk tube was then sealed with a Teflon lined cap and put into a cooled bath (−10 °C). After stirring for 5 min, bormdifluoroacetate 2a (3.0 equiv, 0.6 mmol) was added to the reaction mixture, and the Schlenk tube was then resealed with a Teflon lined cap and put back into the cooled bath (−10 °C). After stirring for another 12 h, the reaction mixture was diluted with ethyl acetate (5 mL). The solvent was removed under reduced pressure, and the residue was purified by flash column chromatography on silica gel to give the desired product.

Data availability

The authors declare that all the data supporting the findings of this research are available within the article and its supplementary information.

References

Müller, K., Faeh, C. & Diederich, F. Fluorine in pharmaceuticals: looking beyond intuition. Science 317, 1881–1886 (2007).
Article ADS Google Scholar
Mikami, K., Itoh, Y. & Yamanaka, M. Fluorinated carbonyl and olefinic compounds: basic character and asymmetric catalytic reactions. Chem. Rev. 104, 1–16 (2004).
Article CAS Google Scholar
Uneyama, K., Katagiri, T. & Amii, H. α-trifluoromethylated carbanion synthons. Acc. Chem. Res. 41, 817–829 (2008).
Article CAS Google Scholar
Ma, J.-A. & Cahard, D. Asymmetric fluorination, trifluoromethylation, and perfluoroalkylation reactions. Chem. Rev. 104, 6119–6146 (2004).
Article CAS Google Scholar
Zhang, C.-P., Chen, Q.-Y., Guo, Y., **ao, J.-C. & Gu, Y.-C. Progress in fluoroalkylation of organic compounds via sulfinatodehalogenation initiation system. Chem. Soc. Rev. 41, 4536–4559 (2012).
Article CAS Google Scholar
Liang, T., Neumann, C. N. & Ritter, T. Introduction of fluorine and fluorine-containing functional groups. Angew. Chem. Int. Ed. 52, 8214–8264 (2013).
Article CAS Google Scholar
Ni, C., Hu, M. & Hu, J. Good partnership between sulfur and fluorine: sulfur-based fluorination and fluoroalkylation reagents for organic synthesis. Chem. Rev. 115, 765–825 (2015).
Article CAS Google Scholar
Belhomme, M.-C., Besset, T., Poisson, T. & Pannecoucke, X. Recent progress toward the introduction of functionalized difluoromethylated building blocks onto C(sp²) and C(sp) centers. Chem. Eur. J. 21, 12836–12865 (2015).
Article CAS Google Scholar
Feng, Z., **ao, Y.-L. & Zhang, X. Transition-metal (Cu, Pd, Ni)-catalyzed difluoroalkylation via cross-coupling with difluoroalkyl halides. Acc. Chem. Res. 51, 2264–2278 (2018).
Article CAS Google Scholar
Nagib, D. A., Scott, M. E. & MacMillan, D. W. C. Enantioselective α-trifluoromethylation of aldehydes via photoredox organocatalysis. J. Am. Chem. Soc. 131, 10875–10877 (2009).
Article CAS Google Scholar
Shibata, N., Mizuta, S. & Kawai, H. Recent advances in enantioselective trifluoromethylation reactions. Tetrahedron.: Asymmetry 19, 2633–2644 (2008).
Article CAS Google Scholar
Cho, E. J. et al. The palladium-catalyzed trifluoromethylation of aryl chlorides. Science 328, 1679–1681 (2010).
Article ADS CAS Google Scholar
Guo, C., Wang, R.-W. & Qing, F.-L. Palladium catalyzed direct α-arylation of α,α-difluoroketones with aryl bromides. J. Fluor. Chem. 143, 135–142 (2012).
Article CAS Google Scholar
Feng, Z., Min, Q.-Q., **ao, Y.-L., Zhang, B. & Zhang, X. Palladium-catalyzed difluoroalkylation of aryl boronic acids: a new method for the synthesis of aryldifluoromethylated phosphonates and carboxylic acid derivatives. Angew. Chem. Int. Ed. 53, 1669–1673 (2014).
Article CAS Google Scholar
Min, Q.-Q., Yin, Z., Feng, Z., Guo, W.-H. & Zhang, X. Highly selective gem-difluoroallylation of organoborons with bromodifluoromethylated alkenes catalyzed by palladium. J. Am. Chem. Soc. 136, 1230–1233 (2014).
Article CAS Google Scholar
Shao, C., Shi, G., Zhang, Y., Pan, S. & Guan, X. Palladium-catalyzed C-H ethoxycarbonyldifluoromethylation of electron-rich heteroarenes. Org. Lett. 17, 2652–2655 (2015).
Article CAS Google Scholar
Gu, Y., Leng, X. & Sheng, Q. Cooperative dual palladium/silver catalyst for direct difluoromethylation of aryl bromides and iodides. Nat. Commun. 5, 5405–5411 (2014).
Article ADS CAS Google Scholar
Feng, Z., Min, Q.-Q., Fu, X.-P., An, L. & Zhang, X. Chlorodifluoromethane-triggered formation of difluoromethylated arenes catalysed by palladium. Nat. Chem. 9, 918–923 (2017).
Article CAS Google Scholar
Aikawa, K., Serizawa, H., Ishii, K. & Mikami, K. Palladium-catalyzed Negishi cross-coupling reaction of aryl halides with (difluoromethyl)zinc reagent. Org. Lett. 18, 3690–3693 (2016).
Article CAS Google Scholar
Oishi, M., Kondo, H. & Amii, H. Aromatic trifluoromethylation catalytic in copper. Chem. Commun. 45, 1909–1911 (2009).
Article Google Scholar
Feng, Z., Chen, F. & Zhang, X. Copper catalyzed cross-coupling of iodobenzoates with bromozinc-difluorophosphonate. Org. Lett. 14, 1938–1941 (2012).
Article CAS Google Scholar
Belhomme, M.-C., Poisson, T. & Pannecoucke, X. Copper-catalyzed direct C-2 difluoromethylation of furans and benzofurans: access to C-2 CF₂H derivatives. J. Org. Chem. 79, 7205–7211 (2014).
Article CAS Google Scholar
Jiang, X., Chu, L. & Qing, F.-L. Copper-mediated oxidative difluoromethylenation of aryl boronic acids with α-silyldifluoromethylphosphonates: a new method for aryldifluorophosphonates. New J. Chem. 37, 1736–1741 (2013).
Article CAS Google Scholar
Serizawa, H., Ishii, K., Aikawa, K. & Mikami, K. Copper-catalyzed difluoromethylation of aryl iodides with (difluoromethyl)zinc reagent. Org. Lett. 18, 3686–3689 (2016).
Article CAS Google Scholar
Gao, X., **ao, Y.-L., Wan, X. & Zhang, X. Copper-catalyzed highly stereoselective trifluoromethylation and difluoroalkylation of secondary propargyl sulfonates. Angew. Chem. Int. Ed. 57, 3187–3191 (2018).
Article CAS Google Scholar
Ivanova, M. V., Bayle, A., Besset, T., Poisson, T. & Pannecoucke, X. Copper-mediated formation of aryl, heteroaryl, vinyl and alkynyl difluoromethylphosphonates: a general approach to fluorinated phosphate mimics. Angew. Chem. Int. Ed. 54, 13406–13410 (2015).
Article CAS Google Scholar
Jiang, X., Chu, L. & Qing, F.-L. Copper-mediated oxidative cross-coupling reaction of terminal alkynes with α-silyldifluoromethylphosphonates: an efficient method for α,α-difluoropropargylphosphonates. Org. Lett. 14, 2870–2873 (2014).
Article Google Scholar
Belhomme, M.-C., Poisson, T. & Pannecoucke, X. Copper catalyzed β-difluoroacetylation of dihydropyrans and glycals by means of direct C–H functionalization. Org. Lett. 15, 3428–3431 (2013).
Article CAS Google Scholar
Zhu, J., Ni, C., Gao, B. & Hu, J. Copper(0)-mediated fluoroalkylation of iodobenzene with 2-bromo-1,1,2,2-tetrafluoroethyl compounds: investigation on the influence of R substituent on the reactivity of RCF₂Cu species. J. Fluor. Chem. 171, 139–147 (2015).
Article CAS Google Scholar
He, Z. et al. Copper-mediated trifluoromethylation of propiolic acids: facile synthesis of α-trifluoromethyl ketones. Chem. Sci. 4, 3478–3483 (2013).
Article CAS Google Scholar
Qi, Q., Shen, Q. & Lu, L. Copper-mediated aerobic fluoroalkylation of arylboronic acids with fluoroalkyl iodides at room temperature. J. Am. Chem. Soc. 134, 6548–6551 (2012).
Article CAS Google Scholar
Hu, M., Ni, C. & Hu, J. Copper-mediated trifluoromethylation of α-diazo esters with TMSCF₃: the important role of water as a promoter. J. Am. Chem. Soc. 134, 15257–15260 (2012).
Article CAS Google Scholar
Moselage, M., Li, J. & Ackermann, L. Cobalt-catalyzed C–H activation. ACS Catal. 6, 498–525 (2016).
Article CAS Google Scholar
Cahiez, G. & Moyeux, A. Cobalt-catalyzed cross-coupling reactions. Chem. Rev. 110, 1435–1462 (2010).
Article CAS Google Scholar
Su, B., Cao, Z.-C. & Shi, Z.-J. Exploration of earth-abundant transition metals (Fe, Co, and Ni) as catalysts in unreactive chemical bond activations. Acc. Chem. Res. 48, 886–896 (2015).
Article CAS Google Scholar
Liang, Y. & Fu, G. C. Catalytic asymmetric synthesis of tertiary alkyl fluorides: Negishi cross-couplings of racemic α,α-dihaloketones. J. Am. Chem. Soc. 136, 5520–5524 (2016).
Article Google Scholar
Jiang, X., Sakthivel, S., Kulbitski, K., Nisnevich, G. & Gandelman, M. Efficient synthesis of secondary alkyl fluorides via suzuki cross-coupling reaction of 1-Halo-1-fluoroalkanes. J. Am. Chem. Soc. 136, 9548–9551 (2014).
Article CAS Google Scholar
Su, Y.-M., Feng, G.-S., Wang, Z.-Y., Lan, Q. & Wang, X.-S. Nickel-catalyzed monofluoromethylation of aryl boronic acids. Angew. Chem. Int. Ed. 54, 6003–6007 (2015).
Article CAS Google Scholar
Schwaebe, M. K., McCarthy, J. R. & Whitten, J. P. Nickel(0)-catalyzed coupling of vinylzirconiums to α-bromo-α,α-difluoro esters Convenient generation of a functionalized allyldifluoro moiety. Tetrahedron Lett. 41, 791–794 (2000).
Article CAS Google Scholar
Sheng, J., Ni, H.-Q., Liu, G., Li, Y. & Wang, X.-S. Combinatorial nickel-catalyzed monofluoroalkylation of aryl boronic acids with unactivated fluoroalkyl iodides. Org. Lett. 19, 4480–4483 (2017).
Article CAS Google Scholar
Sheng, J., Ni, H.-Q., Zhang, H.-R., Wang, Y.-N. & Wang, X.-S. Nickel-catalyzed reductive cross-coupling of aryl halides with monofluoroalkyl halides for late-stage monofluoroalkylation. Angew. Chem. Int. Ed. 57, 7634–7639 (2018).
Article CAS Google Scholar
Gu, J.-W., Min, Q.-Q., Yu, L.-C. & Zhang, X. Tandem difluoroalkylation-arylation of enamides catalyzed by nickel. Angew. Chem. Int. Ed. 55, 12270–12274 (2016).
Article CAS Google Scholar
**ao, Y.-L., Guo, W.-H., He, G.-Z., Pan, Q. & Zhang, X. Nickel-catalyzed cross-coupling of functionalized difluoromethyl bromides and chlorides with aryl boronic acids: a general method for difluoroalkylated arenes. Angew. Chem. Int. Ed. 53, 9909–9913 (2014).
Article CAS Google Scholar
Xu, C. et al. Difluoromethylation of (hetero)aryl chlorides with chlorodifluoromethane catalyzed by nickel. Nat. Commun. 9, 1170–1179 (2018).
Article ADS Google Scholar
An, L., **ao, Y.-L., Zhang, S. & Zhang, X. Bulky diamine ligand promotes cross-coupling of difluoroalkyl bromides by iron catalysis. Angew. Chem. Int. Ed. 57, 6921–6925 (2018).
Article CAS Google Scholar
Lin, X., Zheng, F. & Qing, F.-L. Iron-catalyzed cross-coupling reactions between arylzinc reagents and alkyl halides bearing β-fluorines. Organometallics 31, 1578–1582 (2012).
Article CAS Google Scholar
Miao, W. et al. Iron-catalyzed difluoromethylation of arylzincs with difluoromethyl 2-pyridyl sulfone. J. Am. Chem. Soc. 140, 880–883 (2018).
Article CAS Google Scholar
Ohtsuka, Y. & Yamakawa, T. Direct ethoxycarbonyldifluoromethylation of aromatic compounds using Fenton reagent. Tetrahedron 67, 2323–2331 (2011).
Article CAS Google Scholar
Araki, K. & Inoue, M. Cobalt-catalyzed cross-coupling reaction of arylzinc reagents with ethyl bromodifluoroacetate. Tetrahedron 69, 3913–3918 (2013).
Article CAS Google Scholar
Ohtsuka, Y. & Yamakawa, T. Cobalt/diamine-catalyzed 1,1-difluoroethylation and 2,2,2-trifluoroethylation of aryl Grignard reagents with corresponding fluoroalkyl halides. J. Fluor. Chem. 185, 96–102 (2016).
Article CAS Google Scholar
Chou, T. S. et al. Stereospecific synthesis of 2-deoxy-2,2-difluororibonolactone and its use in the preparation of 2′-Deoxy-2′,2′-difluoro-β-D-ribofuranosyl pyrimidine nucleosides: the key role of selective crystallization. Synthesis 6, 565–570 (1992).
Article Google Scholar
Yue, X., Qiu, X.-L. & Qing, F.-L. Synthesis of 2′,3′-dideoxy-6′,6′-difluoro-3′-azanucleosides. J. Fluor. Chem. 129, 866–874 (2008).
Article CAS Google Scholar
Nakayama, K. et al. Synthesis and antifungal activity of rhodopeptin analogues. 2. Modification of the west amino acid moiety. Org. Lett. 2, 977–980 (2000).
Article CAS Google Scholar
Uoto, K. et al. Synthesis and structure-activity relationships of novel 2’,2’-difluoro analogues of docetaxel. Chem. Pharm. Bull. 45, 1793–1804 (1997).
Article CAS Google Scholar
Fujikawa, K., Fujioka, Y., Kobayashi, A. & Amii, H. A new method for aromatic difluoromethylation: copper-catalyzed cross-coupling and decarboxylation sequence from aryl iodides. Org. Lett. 13, 5560–5563 (2011).
Article CAS Google Scholar
Ge, S., Arlow, S. I., Mormino, M. G. & Hartwig, J. F. Pd-catalyzed α-arylation of trimethylsilyl enolates of α,α-difluoroacetamides. J. Am. Chem. Soc. 136, 14401–14404 (2014).
Article CAS Google Scholar
Xu, L. & Vicic, D. A. Direct difluoromethylation of aryl halides via base metal catalysis at room temperature. J. Am. Chem. Soc. 138, 2536–2539 (2016).
Article CAS Google Scholar
Aikawa, K., Maruyama, K., Nitta, J., Hashimoto, R. & Mikami, K. Siladifluoromethylation and difluoromethylation onto C(sp³), C(sp²), and C(sp) centers using ruppert–prakash reagent and fluoroform. Org. Lett. 18, 3354–3357 (2016).
Article CAS Google Scholar
An, L., Xu, C. & Zhang, X. Highly selective nickel-catalyzed gem-difluoropropargylation of unactivated alkylzinc reagents. Nat. Commun. 8, 1460–1468 (2017).
Article ADS Google Scholar
Cinderella, A. P., Vulovic, B. & Watson, D. A. Palladium-catalyzed cross-coupling of silyl electrophiles with alkylzinc halides: a Silyl-Negishi reaction. J. Am. Chem. Soc. 139, 7741–7744 (2017).
Article CAS Google Scholar
Luo, Z. et al. Synthesis and evaluation of multi-target-directed ligands against Alzheimer’s disease based on the fusion of donepezil and ebselen. J. Med. Chem. 56, 9089–9099 (2013).
Article CAS Google Scholar
Chen, Q.-A., Kim, D. K. & Dong, V. M. Regioselective hydroacylation of 1,3-Dienes by cobalt catalysis. J. Am. Chem. Soc. 136, 3772–3775 (2014).
Article CAS Google Scholar
Liebeskind, L. S., Baysdon, S. L., South, M. S., Iyer, S. & Leeds, J. P. The development of an organotransition metal synthesis of quinones. Tetrahedron 41, 5839–5853 (1985).
Article CAS Google Scholar
Fillon, H., Gosmini, C. & Périchon, J. New chemical synthesis of functionalized arylzinc compounds from aromatic or thienyl bromides under mild conditions using a simple cobalt catalyst and zinc dust. J. Am. Chem. Soc. 125, 3867–3870 (2003).
Article CAS Google Scholar
**, M.-Y. & Yoshikai, N. Cobalt−Xantphos-catalyzed, LiCl-mediated preparation of arylzinc reagents from aryl iodides, bromides, and chlorides. J. Org. Chem. 76, 1972–1978 (2011).
Article CAS Google Scholar
Brennan, M. R., Kim, D. & Fout, A. R. A synthetic and mechanistic investigation into the cobalt(I) catalyzed amination of aryl halides. Chem. Sci. 5, 4831–4839 (2014).
Article CAS Google Scholar

Download references

Acknowledgements

We gratefully acknowledge the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB20000000), the National Basic Research Program of China (973 Program 2015CB856600), the National Science Foundation of China (21772187, 21522208) for financial support.

Author information

These authors contributed equally: Chao Li, Yi-Xuan Cao.

Authors and Affiliations

Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, Center for Excellence in Molecular Synthesis of CAS, University of Science and Technology of China, Hefei, Anhui, 230026, China
Chao Li, Yi-Xuan Cao, Rui Wang, Yi-Ning Wang, Quan Lan & **-Sheng Wang

Authors

Chao Li
View author publications
You can also search for this author in PubMed Google Scholar
Yi-Xuan Cao
View author publications
You can also search for this author in PubMed Google Scholar
Rui Wang
View author publications
You can also search for this author in PubMed Google Scholar
Yi-Ning Wang
View author publications
You can also search for this author in PubMed Google Scholar
Quan Lan
View author publications
You can also search for this author in PubMed Google Scholar
**-Sheng Wang
View author publications
You can also search for this author in PubMed Google Scholar

Contributions

C.L. and Y.-X.C. designed and performed the experiments. R.W., Y.-N.W., and Q.L. helped to complete the experiments. X.-S.W. directed the project and wrote the manuscript. All authors interpreted the results on the manuscript.

Corresponding author

Correspondence to **-Sheng Wang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Supplementary Information

Peer Review File

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Cite this article

Li, C., Cao, YX., Wang, R. et al. Cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides. Nat Commun 9, 4951 (2018). https://doi.org/10.1038/s41467-018-07525-y

Download citation

Received: 03 August 2018
Accepted: 08 November 2018
Published: 23 November 2018
DOI: https://doi.org/10.1038/s41467-018-07525-y
Springer Nature Limited

This article is cited by

Organozinc pivalates for cobalt-catalyzed difluoroalkylarylation of alkenes
- **nyi Cheng
- **ngchen Liu
- Jie Li
Nature Communications (2021)

Cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides

From

Abstract

Similar content being viewed by others

Organozinc pivalates for cobalt-catalyzed difluoroalkylarylation of alkenes

α-Fluorination of carbonyls with nucleophilic fluorine

Copper-catalysed difluorocarbene transfer enables modular synthesis

Introduction

Discussion

Methods

General procedure for the cobalt-catalyzed cross-coupling

Data availability

References

Acknowledgements

Author information

Authors and Affiliations

Contributions

Corresponding author

Ethics declarations

Competing interests

Additional information

Electronic supplementary material

Supplementary Information

Peer Review File

Rights and permissions

About this article

Cite this article

This article is cited by

Organozinc pivalates for cobalt-catalyzed difluoroalkylarylation of alkenes

Navigation

Cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides

From

Abstract

Similar content being viewed by others

Organozinc pivalates for cobalt-catalyzed difluoroalkylarylation of alkenes

α-Fluorination of carbonyls with nucleophilic fluorine

Copper-catalysed difluorocarbene transfer enables modular synthesis

Introduction

Discussion

Methods

General procedure for the cobalt-catalyzed cross-coupling

Data availability

References

Acknowledgements

Author information

Authors and Affiliations

Contributions

Corresponding author

Ethics declarations

Competing interests

Additional information

Electronic supplementary material

Supplementary Information

Peer Review File

Rights and permissions

About this article

Cite this article

Share this article

This article is cited by

Organozinc pivalates for cobalt-catalyzed difluoroalkylarylation of alkenes

Search

Navigation