Synthesis, Table of Contents Synthesis 2021; 53(22): 4297-4307DOI: 10.1055/s-0037-1610774 special topic Special Issue dedicated to Prof. Sarah Reisman, recipient of the 2019 Dr. Margaret Faul Women in Chemistry Award Simple Synthesis of Fluorinated Ene-Ynes via In Situ Generation of Allenes Joseph A. Jaye , Ellen M. Sletten ∗ Recommend Article Abstract Buy Article All articles of this category Abstract Fluorination of small molecules is a key route toward modulating reactivity and bioactivity. The 1,3 ene-yne functionality is an important synthon towards complex products, as well as a common functionality in biologically active molecules. Here, we present a new synthetic route towards fluorinated ene-ynes from simple starting materials. We employ gas chromatography-mass spectrometry analysis to probe the sequential eliminations necessary for this transformation and observe an allene intermediate. The ene-yne products are sufficiently fluorous to enable purification via fluorous extraction. This methodology will allow facile access to functional, fluorous ene-ynes. Key words Key wordsfluorous - ene-yne - allene - sequential elimination Full Text References References 1 Wang J, Sánchez-Roselló M, Aceña JL, Del Pozo C, Sorochinsky AE, Fustero S, Soloshonok VA, Liu H. Chem. Rev. 2014; 114: 2432 2 Gillis EP, Eastman KJ, Hill MD, Donnelly DJ, Meanwell NA. J. Med. Chem. 2015; 58: 8315 3 Nyffeler PT, Durón SG, Burkart MD, Vincent SP, Wong C.-HS. Angew. Chem. Int. Ed. 2005; 44: 192 4 Meyer D, Jangra H, Walther F, Zipse H, Renaud PA. Nat. Commun. 2018; 9: 4888 5 Ma JA, Cahard D. J. Fluorine Chem. 2007; 128: 975 6 Alonso C, Martínez De Marigorta E, Rubiales G, Palacios F. Chem. Rev. 2015; 115: 1847 7 Charpentier J, Früh N, Togni A. Chem. Rev. 2015; 115: 650 8 Liu X, Xu C, Wang M, Liu Q. Chem. Rev. 2015; 115: 683 9 Dolbier WR. Chem. Rev. 1996; 96: 1557 10 Zhang C.-P, Chen Q.-Y, Guo Y, Xiao J.-C, Gu Y.-C. Chem. Soc. Rev. 2012; 41: 4536 11 Zhang W, Huang W, Hu J. Angew. Chem. Int. Ed. 2009; 48: 9858 12 Couve-Bonnaire S, Cahard D, Pannecoucke X. Org. Biomol. Chem. 2007; 5: 1151 13 Tellier F, Sauvêtre R, Normant JF. J. Organomet. Chem. 1989; 364: 17 14 Yoshida M, Yoshikawa S, Fukuhara T, Yoneda N, Hara S. Tetrahedron 2001; 57: 7143 15 Camps F, Fabrias G, Guerrero A. Tetrahedron 1986; 42: 3623 16 Welch JT. Tetrahedron 1987; 43: 3123 17 Camps F, Fabrias G, Gasol V, Guerrero A, Hern R. J. Chem. Ecol. 1988; 14: 1331 18 Kumar R, Zajc B. J. Org. Chem. 2012; 77: 8417 19 Jeanne-Julien L, Masson G, Kouoi R, Regazzetti A, Genta-Jouve G, Gandon V, Roulland E. Org. Lett. 2019; 21: 3136 20 Mei YQ, Liu JT. Tetrahedron 2008; 64: 8801 21 Konno T, Kishi M, Ishihara T, Yamada S. Tetrahedron 2014; 70: 2455 22 Konno T, Kishi M, Ishihara T, Yamada S. J. Fluorine Chem. 2013; 156: 144 23 Dai D.-T, Xu J.-L, Chen Z.-Y, Wang Z.-L, Xu Y.-H. Org. Lett. 2021; 23: 1898 24 Yang C, Liu ZL, Dai DT, Li Q, Ma WW, Zhao M, Xu YH. Org. Lett. 2020; 22: 1360 25 Qi S, Gao S, Xie X, Yang J, Zhang J. Org. Lett. 2020; 22: 5229 26 Shen H, Xiao H, Zhu L, Li C. Synlett 2020; 31: 41 27 Huang J, Jia Y, Li X, Duan J, Jiang Z.-X, Yang Z. Org. Lett. 2021; 23: 2314 28 Fujino T, Hinoue T, Usuki Y, Satoh T. Org. Lett. 2016; 18: 5688 29 Jayaraman A, Lee S. Org. Lett. 2019; 21: 7923 30 Eddarir S, Mestdagh H, Rolando C. Tetrahedron Lett. 1991; 32: 69 31 Wang Y, Xu J, Burton DJ. J. Org. Chem. 2006; 71: 7780 32 Zapata AJ, Gu Y, Hammond GB. J. Org. Chem. 2000; 65: 227 33 Jennings MP, Cork EA, Ramachandran PV. J. Org. Chem. 2000; 65: 8763 34 Slodowicz M, Barata-Vallejo S, Vázquez A, Nudelman NS, Postigo A. J. Fluorine Chem. 2012; 135: 137 35 Rong G, Keese R. Tetrahedron Lett. 1990; 31: 5615 36 Xu T, Cheung CW, Hu X. Angew. Chem. Int. Ed. 2014; 53: 4910 37 Jaye JA, Sletten EM. ACS Macro Lett. 2020; 9: 410 38 Ji Y.-L, Luo J.-J, Lin J.-H, Xiao J.-C, Gu Y.-C. Org. Lett. 2016; 18: 1000 39 Hung MH. Tetrahedron Lett. 1990; 31: 3703 40 Perscheid M, Schollmeyer D, Nubbemeyer U. Eur. J. Org. Chem. 2011; 5250 41 Rocaboy C, Hampel F, Gladysz JA. Org. Lett. 2002; 67: 6863 42 Yang L, Adam C, Cockroft SL. J. Am. Chem. Soc. 2015; 137: 10084 43 Kolb H, Finn MG, Sharlpess BK. Angew. Chem. Int. Ed. 2001; 40: 2004 44 Sinha AK, Equbal D. Asian J. Org. Chem. 2019; 8: 32 45 Ogba OM, Warner NC, O’Leary DJ, Grubbs RH. Chem. Soc. Rev. 2018; 12: 4510 46 Pickens CJ, Johnson SN, Pressnall MM, Leon MA, Berkland CJ. Bioconjugate Chem. 2018; 29: 686 47 Meldal M, Tomøe CW. Chem. Rev. 2008; 108: 2952 48 Pangborn AB, Giardello MA, Grubbs RH, Rosen RK, Timmers FJ. Organometallics 1996; 15: 1518 49 Habib MH, Mallouk TE. J. Fluorine Chem. 1991; 53: 53 50 Umemoto T, Gotoh Y. Bull. Chem. Soc. Jpn. 1986; 59: 439 51 Kharrat S, Laurent P, Blancou H. J. Org. Chem. 2006; 71: 6742 52 Yamazaki T, Yamamoto T, Ichihara R. J. Org. Chem. 2006; 71: 6251 53 Konno T, Chae J, Kanda M, Nagai G, Tamura K, Ishihara T, Yamanaka H. Tetrahedron 2003; 59: 7571 Supplementary Material Supplementary Material Supporting Information
