Hypervalent Iodine Mediated Ring-Opening 1,3-Difluorination of Benzylidenecyclopropanes

Long-Ling Huang; Jia-Yi Li; Qigang Sun; Gui-Yang Zhao; Honggen Wang; Qingjiang Li

doi:10.1055/a-2373-0304

Synthesis, Table of Contents

Synthesis 2025; 57(06): 1230-1236
DOI: 10.1055/a-2373-0304

paper

Bioisosteres

Hypervalent Iodine Mediated Ring-Opening 1,3-Difluorination of Benzylidenecyclopropanes

Long-Ling Huang‡

^aState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, P. R. of China

,

Jia-Yi Li‡

^aState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, P. R. of China

,

Qigang Sun∗

^bDepartment of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital; Affiliated Hainan Hospital of Hainan Medical University, Haikou 570311, P. R. of China

,

Gui-Yang Zhao

^aState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, P. R. of China

,

Honggen Wang

^aState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, P. R. of China

,

Qingjiang Li ∗

^aState Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, P. R. of China

› Author Affiliations

Abstract

All articles of this category

Abstract

1,3-Difluorinated compounds are characterized by their unique conformation, influenced by 1,3-dipolar minimization effects. However, their synthetic methods are relatively limited. Here, a ring-opening 1,3-difluorination of benzylidenecyclopropanes (BCPs) using HF·Py, mediated by an electron-poor hypervalent iodine reagent, which is generated in situ by the oxidation of o-nitroiodobenzene with mCPBA is described. The protocol features mild reaction conditions, good functional group tolerance, and moderate to good yields. Additionally, the synthetic utility of this method is showcased by further transformations of the olefin group and allylic fluoride motif.

Key words

benzylidenecyclopropane - 1,3-difluorination - hypervalent iodine - Olah’s reagent - ring-opening

Full Text

References

References

For selected books and reviews:

1a Uneyama K. Organofluorine Chemistry . Blackwell; Oxford: 2006
1b O’Hagan D. Chem. Soc. Rev. 2008; 37: 308
1c Cahard D, Bizet V. Chem. Soc. Rev. 2014; 43: 135
1d Ni C, Hu J. Chem. Soc. Rev. 2016; 45: 5441

For selected books and reviews:

2a Kirsch P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications. Wiley-VCH; Weinheim: 2013
2b Zhou Y, Wang J, Gu Z, Wang S, Zhu W, Aceña JL, Soloshonok VA, Izawa K, Liu H. Chem. Rev. 2016; 116: 422
2c Meanwell NA. J. Med. Chem. 2018; 61: 5822
2d Mei H, Han J, Fustero S, Medio-Simon M, Sedgwick DM, Santi C, Ruzziconi R, Soloshonok VA. Chem. Eur. J. 2019; 25: 11797
2e Ogawa Y, Tokunaga E, Kobayashi O, Hirai K, Shibata N. iScience 2020; 23: 101467
2f Zhang C, Yan K, Fu C, Peng H, Hawker CJ, Whittaker AK. Chem. Rev. 2022; 122: 167

3a Wu D, Tian A, Sun H. J. Phys. Chem. A 1998; 102: 9901
3b Cheerlavancha R, Lawer A, Cagnes M, Bhadbhade M, Hunter L. Org. Lett. 2013; 15: 5562
3c Scheidt F, Selter P, Santschi N, Holland MC, Dudenko DV, Daniliuc C, Mück-Lichtenfeld C, Hansen MR, Gilmour R. Chem. Eur. J. 2017; 23: 6142

For reviews, see:

4a Kohlhepp SV, Gulder T. Chem. Soc. Rev. 2016; 45: 6270
4b Arnold AM, Ulmer A, Gulder T. Chem. Eur. J. 2016; 22: 8728
4c Han Z.-Z, Zhang C.-P. Adv. Synth. Catal. 2020; 362: 4256
4d Han J, Butler G, Moriwaki H, Konno H, Soloshonok VA, Kitamura T. Molecules 2020; 25: 2116
4e Meyer S, Häfliger J, Gilmour R. Chem. Sci. 2021; 12: 10686
4f Li Q, Liu X.-B, Wang H. Chem. Rec. 2023; 23: e202300231
4g Meyer S, Häfliger J, Gilmour R. Chem. Sci. 2021; 12: 10686

5 Ilchenko NO, Hedberg M, Szabó KJ. Chem. Sci. 2017; 8: 1056
6 Banik SM, Mennie KM, Jacobsen EN. J. Am. Chem. Soc. 2017; 139: 9152
7 Mennie KM, Banik SM, Reichert EC, Jacobsen EN. J. Am. Chem. Soc. 2018; 140: 4797
8 Sharma HA, Mennie KM, Kwan EE, Jacobsen EN. J. Am. Chem. Soc. 2020; 142: 16090
9 Meyer S, Göbel L, Livingstone K, Roblick C, Daniliuc CG, Gilmour R. Tetrahedron 2022; 126: 132925
10 Dean AC, Randle EH, Lacey AJ. D, Giorio GA. M, Doobary S, Cons BD, Lennox A. Angew. Chem. Int. Ed. 2024; 63: in press

11a Lin P.-P, Huang L.-L, Feng S.-X, Yang S, Wang H, Huang Z.-S, Li Q. Org. Lett. 2021; 23: 3088
11b Feng S.-X, Yang S, Tu F.-H, Lin P.-P, Huang L.-L, Wang H, Huang Z.-S, Li Q. J. Org. Chem. 2021; 86: 6800
11c Yang S, Liu X.-B, Feng S.-X, Li Y, Tu F.-H, Huang B, Huang L.-L, Huang Z.-S, Wang H, Li Q. Org. Chem. Front. 2022; 9: 4447
11d Yang S, Wu J.-Y, Lin S, Pu M, Huang Z.-S, Wang H, Li Q. Chem. Asian J. 2023; 18: e202300476

12 Huang L.-L, Lin P.-P, Li Y.-X, Feng S.-X, Tu F.-H, Yang S, Zhao G.-Y, Huang Z.-S, Wang H, Li Q. Org. Lett. 2022; 24: 3389
13 Zhang G, Wang Y, Xu J, Sun J, Sun F, Zhang Y, Zhang C, Du Y. Chem. Sci. 2020; 11: 947

Supplementary Material

Supporting Information