Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000084.xml
Synthesis
DOI: 10.1055/a-2609-9601
DOI: 10.1055/a-2609-9601
paper
Fluorinative Difunctionalization of a Cyclooctene-Fused β-Lactam and Cyclooctene-Fused β-Amino Esters
The authors gratefully acknowledge financial support from the Nemzeti Kutatási Fejlesztési és Innovációs Hivatal (NKFIH/OTKA) (National Research, Development and Innovation Office) of Hungary (FK 145394 and K 142266). We are also grateful for the support provided by the European Union (Project no. RRF-2.3.1-21-2022-00015). This work was supported by the János Bolyai Research Scholarship to M.N. from Magyar Tudományos Akadémia (Hungarian Academy of Sciences).
Abstract
The synthesis of novel arylfluorinated cyclic β-amino acid and β-lactam derivatives is accomplished. Studies on the Pd-catalyzed arylfluorination of the double bond of a cyclooctene-fused azetidine-2-one and various β-amino esters are performed under versatile experimental conditions. The arylfluorinative difunctionalization of a cyclooctene-fused β-lactam, performed with phenylboronic acid in the presence of Selectfluor, palladium diacetate, azacyclic ligands and different solvents, gave a separable mixture of fluorinated and non-fluorinated products. In contrast, arylfluorination of cyclooctane-β-amino esters, performed under similar conditions, proceed with full regio- and stereoselective control, leading to single phenyl-fluorinated products. Possible synthetic pathways for these transformations are also proposed.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2609-9601.
- Supporting Information
Publication History
Received: 11 April 2025
Accepted after revision: 14 May 2025
Accepted Manuscript online:
14 May 2025
Article published online:
11 June 2025
© 2025. Thieme. All rights reserved
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
-
References
- 1a Hangmann WK. J. Med. Chem. 2008; 51: 4359
- 1b O’Hagan D. Chem. Soc. Rev. 2008; 37: 308
- 1c Han J, Remete AM, Dobson LS, Kiss L, Izawa K, Moriwaki H, Soloshonok VA, O’Hagan D. J. Fluorine Chem. 2020; 239: 109639
- 1d Han J, Kiss L, Mei H, Remete AM, Ponikvar-Svet M, Sedgwick DM, Roman R, Fustero S, Moriwaki H, Soloshonok VA. Chem. Rev. 2021; 121: 4678
- 1e Fluorine in Life Sciences: Pharmaceuticals, Medicinal Diagnostics, and Agrochemicals. Haufe G, Leroux FG. Academic Press; London: 2019: 1-90
- 1f Fluorine in Pharmaceutical and Medicinal Chemistry: From Biophysical Aspects to Clinical Applications. Gouverneur V, Müller K. Imperial College Press; London: 2012
- 2a He J, Li Z, Dhawan G, Zhang W, Sorochinsky AE, Butler G, Soloshonok VA, Han J. Chin. Chem. Lett. 2023; 34: 107578
- 2b Sheikhi N, Bahraminejad M, Saeedi M, Mirfazli SS. Eur. J. Med. Chem. 2023; 260: 115758
- 2c Wang Y.-T, Yang P.-C, Zhang Y.-F, Sun J.-F. Eur. J. Med. Chem. 2024; 265: 116124
- 2d Ali S, Zhou J. Eur. J. Med. Chem. 2023; 256: 115476
- 2e Wang Q, Bian Y, Dhawan G, Zhang W, Sorochinsky AE, Makarem A, Soloshonok VA, Han J. Chin. Chem. Lett. 2024; 35: 109780
- 3a
Haufe G.
Chem. Rec. 2023; e202300140
- 3b Mei H, Han J, White S, Graham DJ, Izawa K, Sato T, Fustero S, Meanwell NA, Soloshonok VA. Chem. Eur. J. 2020; 26: 11349
- 3c Remete AM, Nonn M, Fustero S, Fülöp F, Kiss L. Tetrahedron 2018; 74: 6367
- 3d Ni C, Hu J. Chem. Soc. Rev. 2016; 45: 5441
- 3e Hirano K, Saito T, Fujihira Y, Sedgwick DM, Fustero S, Shibata N. J. Org. Chem. 2020; 85: 7976
- 3f Caron S. Org. Process Res. Dev. 2020; 24: 470
- 3g Zhu Y, Han J, Wang J, Shibata N, Sodeoka M, Soloshonok VA, Coelho JA. S, Toste FD. Chem. Rev. 2018; 118: 3887
- 3h Huang M, Zhang C. Org. Lett. 2024; 26: 4158
- 4a Yin G, Mu X, Liu G. Acc. Chem. Res. 2016; 49: 2413
- 4b Liao J, Ouyang L, Lai Y, Luo R. J. Org. Chem. 2020; 85: 5590
- 4c
Aradi K,
Kiss L.
Chem. Eur. J. 2023; e202203499
- 4d Aradi K, Kiss L. Synthesis 2023; 55: 1834
- 4e Remete AM, Nonn M, Novák TT, Csányi D, Kiss L. Chem. Asian J. 2022; 17: e202200395
- 4f Remete AM, Nonn M, Volk B, Kiss L. Synthesis 2022; 54: 3753
- 4g Nonn M, Paizs C, Kiss L. Chem. Rec. 2022; 22: e202200130
- 4h Suarez CC, Colomer I. Chem. Sci. 2023; 14: 12083
- 4i Gauthier R, Paquin JF. Chem. Eur. J. 2023; 29: e202301896
- 4j Qian BY, Zhang W, Lin JH, Cao W, Xiao JC. Chem. Asian J. 2022; 17: e202200184
- 4k Wang X, Lei J, Liu Y, Ye Y, Li J, Sun K. Org. Chem. Front. 2021; 8: 2079
- 5a Remete AM, Nonn M, Kiss L. Chem. Eur. J. 2022; 28: e202202076
- 5b Novák TT, Nguyen TC. T, Gömöry Á, Hornyánszky G, Remete AM, Kiss L. J. Fluorine Chem. 2024; 273: 110239
- 5c Nonn M, Drahos L, Kiss L. ChemistrySelect 2023; 8: e202303898
- 5d He Y, Yang Y, Thornbury RT, Toste FD. J. Am. Chem. Soc. 2015; 137: 12207
- 5e Gong J, Wang Q, Zhu J. Angew. Chem. Int. Ed. 2022; 61: e202211470
- 5f Cao J, Wu H, Wang Q, Zhu J. Nat. Chem. 2021; 13: 671
- 6a Reshma, Sitanshu, Bhalla J. Tetrahedron 2024; 167: 134230
- 6b Skibinska M, Warowicka A, Koroniak H, Cytlak T, Crousse B. Org. Lett. 2024; 26: 692
- 6c Nonn M, Kiss L. Asian J. Org. Chem. 2023; 12: e202300526
- 6d Sanmartin AS, Ardil LA. Org. Biomol. Chem. 2023; 21: 3296
- 6e Carosso S, Liu R, Miller PA, Hecker SJ, Glinka T, Miller MJ. J. Med. Chem. 2017; 60: 8933
- 6f Decuyper L, Jukic M, Sosic I, Amoroso AM, Verlaine O, Joris B, Gobec S, D’hooghe M. Chem. Asian J. 2020; 15: 51
- 6g Fu D.-J, Zhang Y.-F, Chang AQ, Li J. Eur. J. Med. Chem. 2020; 201: 112510
- 6h Hosseyni S, Jarrahpour A. Org. Biomol. Chem. 2018; 16: 6840
- 7a Kiss L, Fülöp F. Chem. Rev. 2014; 114: 1116
- 7b Liu J, Han J, Izawa K, Sato T, White S, Meanwell NA, Soloshonok VA. Eur. J. Med. Chem. 2020; 208: 112736
- 7c Wang S, Ying Z, Huang Y, Li Y, Hu M, Kang K, Wang H, Shao J, Wu G, Yu Y, Du Y, Chen W. Eur. J. Med. Chem. 2023; 250: 115185
- 7d Watson RJ, Bamborough P, Barnett H, Chung C, Davis R, Gordon L, Grandi P, Petretich M, Phillipou A, Prinjha RK, Rioja I, Soden P, Werner T, Demont EH. J. Med. Chem. 2020; 63: 9045
- 7e Granberg KH, Sakamaki S, Fuchigami R, Niwa Y, Fujio M, Kato H, Bergstrom F, Larsson N, Persson M, Villar IC, Fujita T, Sugikawa E, Althage M, Yano N, Yokoyama Y, Kimura J, Lal M, Mochida H. J. Med. Chem. 2024; 67: 4442
- 7f Richard-Bildstein S, Aissaoui H, Pothier J, Schafer G, Gnerre C, Lindenberg E, Lehembre F, Pouzol L, Guerry P. J. Med. Chem. 2020; 63: 15864
- 7g Cooper M, Llinas A, Hansen P, Caffrey M, Ray A, Sjodin S, Shamovsk I, Wada H, Jensen TJ, Sivars U, Hultin L, Andersson U, Lundqvist S, Gedda K, Jinton L, Krutrok N, Lewis R, Jansson P, Gardelli C. J. Med. Chem. 2020; 63: 9705
- 7h Kiss L, Mándity IM, Fülöp F. Amino Acids 2017; 49: 1441
- 7i Semghouli A, Nonn M, Remete AM, Fustero S, Kiss L. Chem. Rec. 2023; 23: e202300279
- 8a Zhang DW, Zhao X, Hou JL, Li ZT. Chem. Rev. 2012; 112: 5271
- 8b Morimoto J, Kim J, Kuroda D, Nagatoishi S, Tsumoto K, Sando S. J. Am. Chem. Soc. 2020; 142: 2277
- 8c Mándity IM, Monsignori A, Fülöp L, Forró E, Fülöp F. Chem. Eur. J. 2014; 20: 4591
- 8d Tan G, Das M, Keum H, Bellotti P, Daniliuc C, Glorius F. Nat. Chem. 2022; 14: 1174
- 8e Ruffoni A, Ferri N, Bernini SK, Ricci C, Coesini A, Maffucci I, Clerici F, Contini A. J. Med. Chem. 2014; 57: 2953
- 9a Zhou M, Feng Z, Zhang X. Chem. Commun. 2023; 59: 1434
- 9b Bonetti A, Pellegrino S, Das P, Yuran S, Bucci R, Ferri N, Meneghetti F, Castellano C, Reches M, Gelmi ML. Org. Lett. 2015; 17: 4468
- 9c Brittain WD. G, Lloyd CM, Cobb SL. J. Fluorine Chem. 2020; 239: 109630
- 9d Leppkes J, Hohmann T, Koksch B. J. Fluorine Chem. 2020; 232: 109453
- 9e
Huhmann S,
Koksch B.
Eur. J. Org. Chem. 2018; 3667
- 10 Pracht P, Bohle F, Grimme S. Phys. Chem. Chem. Phys. 2020; 22: 7169
- 11 Neese F. WIREs Comput. Mol. Sci. 2012; 2: 73