ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
Recently Viewed
You have not visited any articles yet, Please visit some articles to see contents here.
CONTENT TYPES

Figure 1Loading Img

Catalytic Enantioselective Synthesis of Difluorinated Alkyl Bromides

Cite this: J. Am. Chem. Soc. 2020, 142, 35, 14831–14837
Publication Date (Web):August 17, 2020
https://doi.org/10.1021/jacs.0c07043
Copyright © 2020 American Chemical Society
Article Views
9300
Altmetric
-
Citations
LEARN ABOUT THESE METRICS
Read OnlinePDF (2 MB)
Supporting Info (3)»

Abstract

Abstract Image

We report an iodoarene-catalyzed enantioselective synthesis of β,β-difluoroalkyl bromide building blocks. The transformation involves an oxidative rearrangement of α-bromostyrenes, utilizing HF–pyridine as the fluoride source and m-CPBA as the stoichiometric oxidant. A catalyst decomposition pathway was identified, which, in tandem with catalyst structure–activity relationship studies, facilitated the development of an improved catalyst providing higher enantioselectivity with lower catalyst loadings. The versatility of the difluoroalkyl bromide products was demonstrated via highly enantiospecific substitution reactions with suitably reactive nucleophiles. The origins of enantioselectivity were investigated using computed interaction energies of simplified catalyst and substrate structures, providing evidence for both CH−π and π–π transition state interactions as critical features.

Supporting Information

ARTICLE SECTIONS
Jump To

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.0c07043.

  • Experimental procedures and characterization data (PDF)

  • Computational procedures and data (PDF)

  • Crystallographic data for derivatized product S4 (CIF)

Terms & Conditions

Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

Cited By


This article is cited by 23 publications.

  1. Long-Ling Huang, Peng-Peng Lin, Yu-Xin Li, Si-Xin Feng, Fang-Hai Tu, Shuang Yang, Gui-Yang Zhao, Zhi-Shu Huang, Honggen Wang, Qingjiang Li. Oxidative Fluoroarylation of Benzylidenecyclopropanes with HF·Py and Aryl Iodides via Iodonio-[3,3]-Rearrangement. Organic Letters 2022, 24 (18) , 3389-3394. https://doi.org/10.1021/acs.orglett.2c01150
  2. Yang Wang, Yuan-Yuan Sun, Yi-Mo Cui, Ying-Xin Yu, Zheng-Guang Wu. Construction of Benzimidazolone Derivatives via Aryl Iodide Catalyzed Intramolecular Oxidative C–H Amination. The Journal of Organic Chemistry 2022, 87 (5) , 3234-3241. https://doi.org/10.1021/acs.joc.1c02929
  3. Chunngai Hui, Lukas Brieger, Carsten Strohmann, Andrey P. Antonchick. Stereoselective Synthesis of Cyclobutanes by Contraction of Pyrrolidines. Journal of the American Chemical Society 2021, 143 (45) , 18864-18870. https://doi.org/10.1021/jacs.1c10175
  4. Shuang Yang, Shoujie Shi, Yuhang Chen, Zhenhua DING. Synthesis of Dihydroxazines and Fluorinated Oxazepanes Using a Hypervalent Fluoroiodine Reagent. The Journal of Organic Chemistry 2021, 86 (20) , 14004-14010. https://doi.org/10.1021/acs.joc.1c00159
  5. Si-Xin Feng, Shuang Yang, Fang-Hai Tu, Peng-Peng Lin, Long-Ling Huang, Honggen Wang, Zhi-Shu Huang, Qingjiang Li. Iodine(III)-Mediated Fluorination/Semipinacol Rearrangement Cascade of 2-Alkylidenecyclobutanol Derivatives: Access to β-Monofluorinated Cyclopropanecarbaldehydes. The Journal of Organic Chemistry 2021, 86 (9) , 6800-6812. https://doi.org/10.1021/acs.joc.1c00578
  6. Lu-Wen Zhang, Xiao-Jun Deng, Dong-Xu Zhang, Qin-Qin Tian, Wei He. Aminolactonization of Unactivated Alkenes Catalyzed by Aryl Iodine. The Journal of Organic Chemistry 2021, 86 (7) , 5152-5165. https://doi.org/10.1021/acs.joc.1c00074
  7. Chisato Wata, Takuya Hashimoto. Organoiodine-Catalyzed Enantioselective Intermolecular Oxyamination of Alkenes. Journal of the American Chemical Society 2021, 143 (4) , 1745-1751. https://doi.org/10.1021/jacs.0c11440
  8. Qiang Wang, Marvin Lübcke, Maria Biosca, Martin Hedberg, Lars Eriksson, Fahmi Himo, Kálmán J. Szabó. Enantioselective Construction of Tertiary Fluoride Stereocenters by Organocatalytic Fluorocyclization. Journal of the American Chemical Society 2020, 142 (47) , 20048-20057. https://doi.org/10.1021/jacs.0c09323
  9. Muhammet Uyanik, Kazuaki Ishihara. ASYMMETRIC HYPERVALENT IODINE CATALYSIS. 2022,,, 243-276. https://doi.org/10.1002/9781119736424.ch7
  10. John M. Ovian, Eric N. Jacobsen. Catalytic Alkene Difunctionalization Reactions. 2022,,, 243-274. https://doi.org/10.1002/9783527829569.ch9
  11. Wen-Xin Lv, Yin Li, Yuan-Hong Cai, Dong-Hang Tan, Zhan Li, Ji-Lin Li, Qingjiang Li, Honggen Wang. Hypervalent iodine-mediated β-difluoroalkylboron synthesis via an unusual 1,2-hydrogen shift enabled by boron substitution. Chemical Science 2022, 13 (10) , 2981-2984. https://doi.org/10.1039/D1SC06508D
  12. Pier Alexandre Champagne. Identifying the true origins of selectivity in chiral phosphoric acid catalyzed N -acyl-azetidine desymmetrizations. Chemical Science 2021, 12 (47) , 15662-15672. https://doi.org/10.1039/D1SC04969K
  13. Weiwei Zhu, Xiang Zhen, Jingyuan Wu, Yaping Cheng, Junkai An, Xingyu Ma, Jikun Liu, Yuji Qin, Hao Zhu, Jijun Xue, Xianxing Jiang. Catalytic asymmetric nucleophilic fluorination using BF3·Et2O as fluorine source and activating reagent. Nature Communications 2021, 12 (1) https://doi.org/10.1038/s41467-021-24278-3
  14. Qiupeng Peng, Bingjia Yan, Fangyi Li, Ming Lang, Bei Zhang, Donghui Guo, Donald Bierer, Jian Wang. Biomimetic enantioselective synthesis of β,β-difluoro-α-amino acid derivatives. Communications Chemistry 2021, 4 (1) https://doi.org/10.1038/s42004-021-00586-z
  15. Stephanie Meyer, Joel Häfliger, Ryan Gilmour. Expanding organofluorine chemical space: the design of chiral fluorinated isosteres enabled by I( i )/I( iii ) catalysis. Chemical Science 2021, 12 (32) , 10686-10695. https://doi.org/10.1039/D1SC02880D
  16. Chisato Wata, Takuya Hashimoto. Organoiodine-Catalyzed Enantioselective Intramolecular Oxy­aminations of Alkenes with N-(Fluorosulfonyl)carbamate. Synthesis 2021, 53 (15) , 2594-2601. https://doi.org/10.1055/s-0037-1610768
  17. Yoshihiro Nishimoto, Masaki Fujie, Junki Hara, Makoto Yasuda. Effect of noncovalent interactions in ion pairs on hypervalent iodines: inversion of regioselectivity in sulfonyloxylactonization. Organic Chemistry Frontiers 2021, 8 (14) , 3695-3704. https://doi.org/10.1039/D1QO00523E
  18. Jia‐Yi Shou, Xiu‐Hua Xu, Feng‐Ling Qing. Chemoselective Hydro(Chloro)pentafluorosulfanylation of Diazo Compounds with Pentafluorosulfanyl Chloride. Angewandte Chemie International Edition 2021, 60 (28) , 15271-15275. https://doi.org/10.1002/anie.202103606
  19. Jia‐Yi Shou, Xiu‐Hua Xu, Feng‐Ling Qing. Chemoselective Hydro(Chloro)pentafluorosulfanylation of Diazo Compounds with Pentafluorosulfanyl Chloride. Angewandte Chemie 2021, 133 (28) , 15399-15403. https://doi.org/10.1002/ange.202103606
  20. Chenglong Li, Yangzhen Liao, Xuemei Tan, Xiaozu Liu, Peijun Liu, Wen-Xin Lv, Honggen Wang. Hypervalent iodine-mediated gem-difluorination of vinyl halides enabled by exclusive 1,2-halo migration. Science China Chemistry 2021, 64 (6) , 999-1003. https://doi.org/10.1007/s11426-021-9965-9
  21. Joel Häfliger, Keith Livingstone, Constantin G. Daniliuc, Ryan Gilmour. Difluorination of α-(bromomethyl)styrenes via I(I)/I(III) catalysis: facile access to electrophilic linchpins for drug discovery. Chemical Science 2021, 12 (17) , 6148-6152. https://doi.org/10.1039/D1SC01132D
  22. Yang Wang, Bing Yang, Xin-Xing Wu, Zheng-Guang Wu. Recent Application of Chiral Aryliodine Based on the 2-Iodo­resorcinol Core in Asymmetric Catalysis. Synthesis 2021, 53 (05) , 889-903. https://doi.org/10.1055/s-0040-1705969
  23. Dayanne R. Carvalho, Alec H. Christian. Modern approaches towards the synthesis of geminal difluoroalkyl groups. Organic & Biomolecular Chemistry 2021, 19 (5) , 947-964. https://doi.org/10.1039/D0OB02374D

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

STEP 1:
Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

MENDELEY PAIRING EXPIRED
Your Mendeley pairing has expired. Please reconnect

This website uses cookies to improve your user experience. By continuing to use the site, you are accepting our use of cookies. Read the ACS privacy policy.

CONTINUE