Photoinduced C-F Bond Cleavage α-Trifluoromethyl Alkenes for the Synthesis of gem-Difluoroalkenes

doi:10.6023/cjoc202512002

Abstract

Herein, we present a highly efficient photoinduced radical addition/defluoroalkylation of dihydroquinazolinones and CF₃-substituted alkenes, affording a diverse set of gem-difluoroalkenes under mild visible-light conditions. This strategy relies on C-C bond cleavage of dihydroquinazolinones to generate alkyl radicals, followed by addition and β-fluoride elimination. This reaction exhibits broad substrate scope, excellent functional group tolerance, and operational simplicity.

Key words: gem-Difluoroalkenes, C-F bond cleavage, Photochemistry, α-Trifluoromethyl alkenes

Cite this article

Wang Bin, Ye Bo, Wang Lei, He Hong, Ma Yongmin. Photoinduced C-F Bond Cleavage α-Trifluoromethyl Alkenes for the Synthesis of gem-Difluoroalkenes[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202512002.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] March, J. in March’s advanced organic chemistry: reactions, mechanisms, and structure. Ed. Smith, M. B. New York, 8^th edn., 2020, pp. 1335–1438.
[2] Bhunia A.; Studer, A. Chem, 2021, 7, 2060-2100.
[3] (a) Zhou X.; Xu Y.; Dong G. Nat. Catal.2021, 4, 703-710.
(b) Zhou X.; Xu Y.; Dong, G. J. Am. Chem. Soc.2021, 143, 20042-20048.
(c) Zhou X.; Yu T.; Dong, G. J. Am. Chem. Soc.2022, 144, 9570-9575.
(d) Zhou X.; Pyle D.; Zhang Z.; Dong, G. Angew. Chem., Int. Ed.2023, 62, e202213691.
[4] (a) Lv X.; Abrams R.; Martin R. Nat. Commun.2022, 13, 2394-2402.
(b) Lv X.; Abrams R.; Martin, R. Angew. Chem., Int. Ed.2023, 62, e202217386.
(c) Cong F.; Mega R. S.; Chen J.; Day C. S.; Martin, R. Angew. Chem., Int. Ed.2023, 62, e202214633.
[5] Li L.; Fang L.; Wu W.; Zhu J. Org. Lett.2020, 22, 5401-5406.
[6] (a) Lee S. C.; Li L. Y.; Tsai Z. N.; Lee Y. H.; Tsao Y. T.; Huang P. G.; Cheng C. K.; Lin H. B.; Chen T. W.; Yang C. H.; Chiu C. C.; Liao, H. H. Org. Lett.2022, 24, 85-89.
(b) Mondal P. P.; Pal A.; Prakash A. K.; Sahoo B. Chem. Commun.2022, 58, 13202-13205.
(c) Wu H.; Chen S.; Xiao D.; Li F.; Zhou K.; Yin X.; Liu C.; He X.; Shang Y. Org. Lett.2023, 25, 1166-1171.
[7] (a) Magueur G.; Crousse B.; Ourévitch M.; Bonnet-Delpon D.; Bégué, J.-P. J. Fluorine Chem.2006, 127, 637-642.
(b) Meanwell, N. A. J. Med. Chem.2011, 54, 2529-2591.
(c) Liu S.; Zhou J.; Yu L.; Liu Y.; Huang Y.; Ouyang Y.; Liu G. K.; Xiu X. H.; Shibata N. Chem. Rev.2025, 125, 4603-4764.
[8] (a) Bégué J.-P.; Bonnet-Delpon D.; Rock, M. H. Tetrahedron Lett.1995, 36, 5003-5006.
(b) Hu M.; Ni C.; Li L.; Han Y.; Hu, J. J. Am. Chem. Soc.2015, 137, 14496-14501.
(c) Fujita T.; Takazawa M.; Sugiyama K.; Suzuki N.; Ichikawa J. Org. Lett.2017, 19, 588-591.
(d) Tian F.; Yan G.; Yu J. Chem. Commun.2019, 55, 13486-13505.
(e) Nowak R.; Robins, M. J. Org. Lett.2005, 7, 721-724.
(f) Zhao Y.; Huang W.; Zhu L.; Hu J. Org. Lett.2010, 12, 1444-1447.
(g) Zheng J.; Lin J.-H.; Cai J.; Xiao J.-C. Chem.-Eur. J.2013, 19, 15261-15266.
(h) Zheng J.; Cai J.; Lin J.-H.; Guo Y.; Xiao J.-C. Chem. Commun.2013, 49, 7513-7515.
[9] (a) Zhang C.; Wang L.; Shi H.; Lin Z.; Wang C. Org. Lett.2022, 24, 3211-3216.
(b) Qiu J.; Wang C.; Zhou L.; Lou Y.; Yang K.; Song Q. Org. Lett.2022, 24, 2446-2451.
(c) Hu Q.; Cheng J.; Wang Y.; Shi J.; Wang B.; Hu P.; Zhao K.; Pan F. Org. Lett.2021, 23, 4457-4462.
(d) Gao Q.; Niu Z.; Chen Y.; Sun J.; Han W.; Wang J.; Yu M.; Zhou M. Org. Lett.2021, 23, 6153-6157.
(e) Zhang C.; Lin Z.; Zhu Y.; Wang, C. J. Am. Chem. Soc.2021, 143, 11602-11610.
(f) Dong H.; Lin Z.; Wang, C. J. Org. Chem.2022, 87, 892-903.
(g) Li L.; Xiao T.; Chen H.; Zhou, L. Chem.- Eur. J.2017, 23, 2249-2254.
(h) Wu L.; Cheng J.; Shen L.; Shen Z.; Loh, T. P. Adv. Synth. Catal.2018, 360, 3894-3899.
(i) Phelan J. P.; Lang S. B.; Sim J.; Berritt S.; Peat A. J.; Billings K.; Fan L.; Molander, G. A. J. Am. Chem. Soc.2019, 141, 3723-3732.
(j) Chen H.; Anand D.; Zhou, L. Asian J. Org. Chem.2019, 8, 661-664.
(k) He, Y.; Anand, D.; Sun, Z.; Zhou, L.Org. Lett. 2019, 21, 3769-3773.
(l) Xia P.; Ye Z.; Hu Y.; Song D.; Xiang H.; Chen X.; Yang H. Org. Lett.2019, 21, 2658-2662.
(m) Anand D.; Sun Z.; Zhou L. Org. Lett.2020, 22, 2371-2375.
(n) Guo Y.; Wu Y.; Wang R.; Song H.; Liu Y.; Wang Q. Org. Lett.2021, 23, 2353-2358.
(o) Aurélie C.; Clémence. A.; Géraldine M. Chem.-Eur. J.2022, 28, e202103337.
(p) Zhang C.; Lin Z.; Zhu Y.; Wang, C. J. Am. Chem. Soc.2021, 143, 11602-11610.
(q) Zhang C.; Wang L.; Shi H.; Lin Z.; Wang C. Org. Lett.2022, 24, 3211-3216.
[10] (a) Wang M.; Pu X.; Zhao Y.; Wang P.; Li Z.; Zhu C.; Shi, Z. J. Am. Chem. Soc.2018, 140, 9061-9065.
(b) Wu X.; Xie F.; Gridnev I.; Zhang W. Org. Lett.2018, 20, 1638-1642.
(c) Lin Z.; Lan Y.; Wang C. Org. Lett.2020, 22, 3509-3514.
(d) Zhu C.; Liu Z.; Tang L.; Zhang H.; Zhang Y.; Walsh P.; Feng C. Nat. Commun.2020, 11, 4860.
(e) Lu X.; Jiang R.; Li J.; Liu C.; Wang Q.; Zhou, H. Org. Biomol. Chem.2020, 18, 3674-3678.
(f) Ding D.; Lan Y.; Lin Z.; Wang C. Org. Lett.2019, 21, 2723-2730.
(g) Lin Z.; Lan Y.; Wang C. ACS Catal.2019, 9, 775-780.
(h) Yue W.; Day C. S.; Martin, R. J. Am. Chem. Soc.2021, 143, 6395-6400.
[11] Lu X.; Wang X.-X.; Gong T.-J.; Pi J.-J.; He S.-J.; Fu Y. Chem. Sci.2019, 10, 809-814.
[12] (a) Lan Y.; Yang F.; Wang C. ACS Catal.2018, 8, 9245-9251.
(b) Lin Z.; Lan Y.; Wang C. Org. Lett.2019, 21, 8316-8322.
(c) Wiles R. J.; Wiles J. P.; Molander, G. A. Chem. Commun.2019, 55, 7599-7602.
[13] (a) Sun Z.; Zhou, L. J. Org. Chem.2022, 87, 4801-4812.
(b) Xiao T.; Li L.; Zhou, L. J. Org. Chem.2016, 81, 7908-7916.
(c) Guo Y.; Wang R.; Song H.; Liu Y.; Wang Q. Org. Lett.2020, 22, 709-713.
[14] (a) Lang S. B.; Wiles R. J.; Kelly, C. B. Angew. Chem. Int. Ed.2017, 56, 15073-15077.
(b) Chen Y.; Ni N.; Cheng D.; Xu X. Tetrahedron Lett.2020, 61, 152425.
(c) Ranjan P.; Pillitteri S.; Coppola G.; Oliva M.; Van der Eycken, E. V.; Sharma, U. K. ACS Catal.2021, 11, 10862-10870.
(d) Yue F.; Ma H.; Song H.; Liu Y.; Dong J.; Wang Q. Chem. Sci.2022, 13, 13466-13474.
(e) Wang B.; Wang C. T.; Li X. S.; Liu X. Y.; Liang, Y. M. Org. Lett.2022, 24, 6566-6570.
(f) Yue F.; Dong J.; Liu Y.; Wang Q. Org. Lett.2021, 23, 7306-7310.
[15] (a) Bag S.; Dhibar A.; Moorthy S.; Ashokan A.; Sahoo B. Org. Lett.2025, 27, 783-788.
(b) He K.; Jin N.; Chen J.; Zheng Y.; Pan F. Org. Lett.2024, 26, 9503-9507.
(c) Bag S.; Ojha S.; Venugopalan S.; Sahoo, B. J. Org. Chem.2023, 88, 12121-12130.
(d) Mondal P. P.; Das S.; Venugopalan S.; Krishnan M.; Sahoo B. Org. Lett.2023, 25, 1441-1446.
(e) Wu H.; Chen S.; Xiao D.; Li F.; Zhou K.; Yin X.; Liu C.; He X.; Shang Y. Org. Lett.2023, 25, 1166-1171.
(f) Yan L.; Zhang T.; Lv Z.; Fu, M. Org. Chem. Front.2023, 10, 6205-6211.
[16] (a) Guan M.; Niu Y.; Shui J.; Chen H.; Wang, L. Org. Lett. 2026, 28,1755-1760.
(b) Luo X.-B.; Wu X.-D.; Wang L.; Li Z.; Hou Z.-W. Chem. Commun.2026, 62, 4346-4349.
(c) Wang F.; Xie X.; Ye B.; Wang L.; Zhu, B. Adv. Synth. Catal.2026, 368, e70306.
(d) Gao R.; Zuo L.; Wang F.; Li C.-Y.; Jiang H.; Li P.; Wang, L. Chin. J. Org. Chem. 2022, 42, 1883-1903.
(e) Mu X.; Guan M.; Niu Y.; Chen H.; Li C.-Y.; Wang, L. Chin. J. Org. Chem.2025, 45, 256-266.

光诱导下三氟甲基烯烃C-F键断裂合成偕二氟烯烃