Expedient Access to Structural Complexity via Radical β-Fragmentation of N–O Bonds

Abstract

Structures containing N–O bonds are well-established precursors of nitrogen- and/or oxygen-centered radicals under visible-light conditions in modern organic synthesis. Whereas both heterolytic and homolytic scissions of N–O bonds have been extensively documented, intrinsic limitations related to substrate structure somewhat restrict their broader application. This paper highlights a novel strategy that synergistically combines a radical-generation process that is independent of the substrate’s redox potential with a radical-induced β-fragmentation of the N–O bond. Subsequent manipulation of the generated nitrogen- or oxygen-centered radicals leads to the successful development of group-transfer carboamination of alkenes, ring-opening functionalization of heterocycles, and efficient trifunctionalization of nonactivated alkenes.

1 Introduction

2 Carboamination of Nonactivated Alkenes

3 Radical-Addition-Induced Ring-Opening Functionalization of 4-Isoxazolines

4 Multisite Functionalization of Alkenes by Merging Cycloaddition and Ring-Opening Functionalization

5 Conclusion

Key words

β-fragmentation - N–O bond scission - radical reactions - halogen-atom transfer - remote functionalization

Publication History

Received: 07 November 2024

Accepted after revision: 17 December 2024

Accepted Manuscript online:
17 December 2024

Article published online:
13 February 2025

• References

• 1a Zard SZ. Chem. Soc. Rev. 2008; 37: 1603
• 1b Xiong T, Zhang Q. Chem. Soc. Rev. 2016; 45: 3069
• 1c Guo J.-J, Hu A, Zuo Z. Tetrahedron Lett. 2018; 59: 2103
• 1d Jia K, Chen Y. Chem. Commun. 2018; 54: 6105
• 1e Chang L, An Q, Duan L, Feng K, Zuo Z. Chem. Rev. 2022; 122: 2429
• 1f Zhu X, Fu H. Chem. Commun. 2021; 57: 9656
• 1g Xiao F, Guo Y, Zeng Y.-F. Adv. Synth. Catal. 2021; 363: 120
• 2a Nakamura I, Terada M. Heterocycles 2014; 89: 845
• 2b Li J, Hu Y, Zhang D, Liu Q, Dong Y, Liu H. Adv. Synth. Catal. 2017; 359: 710
• 2c Lei L, Li C, Mo D. Youji Huaxue 2019; 39: 2989
• 2d Rykaczewski KA, Wearing ER, Blackmun DE, Schindler CS. Nat. Synth. 2022; 1: 24
• 2e Jiang H.-M, Zhao Y.-L, Sun Q, Ouyang X.-H, Li J.-H. Molecules 2023; 28: 1775
• 3a Romero NA, Nicewicz DA. Chem. Rev. 2016; 116: 10075
• 3b Marzo L, Pagire SK, Reiser O, König B. Angew. Chem. Int. Ed. 2018; 57: 10034
• 3c Skubi KL, Blum TR, Yoon TP. Chem. Rev. 2016; 116: 10035
• 3d Shaw MH, Twilton J, MacMillan DW. C. J. Org. Chem. 2016; 81: 6898
• 3e Strieth-Kalthoff F, James MJ, Teders M, Pitzer L, Glorius F. Chem. Soc. Rev. 2018; 47: 7190
• 4a Kärkäs MD. ACS Catal. 2017; 7: 4999
• 4b Chen J.-R, Hu X.-Q, Lu L.-Q, Xiao W.-J. Chem. Soc. Rev. 2016; 45: 2044
• 4c Kwon K, Simons RT, Nandakumar M, Roizen JL. Chem. Rev. 2022; 122: 2353
• 5 Davies J, Morcillo SP, Douglas JJ, Leonori D. Chem. Eur. J. 2018; 24: 12154
• 6 Lee DS, Soni VK, Cho EJ. Acc. Chem. Res. 2022; 55: 2526
• 7a Xu Y, Gao H.-X, Pan C, Shi Y, Zhang C, Huang G, Feng C. Angew. Chem. Int. Ed. 2023; 62: e202310671
• 7b Ge L, Zhang C, Pan C, Wang D.-X, Liu D.-Y, Li Z.-Q, Shem P, Tian L, Feng C. Nat. Commun. 2022; 13: 5938
• 7c Ge L, Wang D.-X, Xing R, Ma D, Walsh PJ, Feng C. Nat. Commun. 2019; 10: 4367
• 7d Tang H.-J, Zhang X, Zhang Y.-F, Feng C. Angew. Chem. Int. Ed. 2020; 59: 5242
• 7e Liu H, Ge L, Wang D.-X, Chen N, Feng C. Angew. Chem. Int. Ed. 2019; 58: 3918
• 7f Cai S.-H, Xie J.-H, Song S, Ye L, Feng C, Loh T.-P. ACS Catal. 2016; 6: 5571
• 7g Li Z.-Q, Zhang C, Feng C. Synlett 2023; 34: 393
• 7h Chen K, Li Z.-Q, Zhu C, Feng C. Trends Chem. 2023; 5: 160
• 8 Jiang H, Studer A. CCS Chem. 2019; 1: 38
• 9a Juliá F, Constantin T, Leonori D. Chem. Rev. 2022; 122: 2292
• 9b Jiang Y, Yin Y, Jiang Z. Chin. J. Org. Chem. 2024; 44: 1733
• 10 Zhang Y, Liu H, Tang L, Tang H.-J, Wang L, Zhu C, Feng C. J. Am. Chem. Soc. 2018; 140: 10695
• 11 Li X, Shui Y, Shen P, Wang Y.-P, Zhang C, Feng C. Chem 2022; 8: 2245
• 12 Liu H, Wang Y.-P, Wang H, Ren K, Liu L, Dang L, Wang C.-Q, Feng C. Angew. Chem. Int. Ed. 2024; 63: e202407928
• 13 Le C, Chen TQ, Liang T, Zhang P, MacMillan DW. C. Science 2018; 360: 1010