R. D. Chambers, M. Parsons, G. Sandford, and R. Bowden, Chem. Commun, vol.11, p.959, 2000.

G. Stavber, M. Zupan, S. Stavber, and . Synlett, , vol.4, p.589, 2009.

J. Graton, G. Compain, F. Besseau, E. Bogdan, J. M. Watts et al., J, vol.2017, issue.12, p.2811

S. Bloom, C. R. Pitts, R. Woltornist, A. Griswold, M. G. Holl et al., Org. Lett, issue.7, p.1722, 2013.

J. Xia, C. Zhu, and C. Chen, J. Am. Chem. Soc, p.17494, 2013.

D. Cantillo, O. De-frutos, J. A. Rinc??n, C. Mateos, and C. O. Kappe, J. Org. Chem, issue.17, p.8486, 2014.

F. Yin, Z. Wang, Z. Li, C. Li, C. Liu et al., J. Am. Chem. Soc, vol.134, p.10401, 2012.

T. J. Barker and D. L. Boger, J. Am. Chem. Soc, vol.2012, issue.33, p.13588

S. Stavber, M. Jereb, and M. Zupan, Synlett, issue.9, p.1375, 1999.

Y. Takeuchi, T. Tarui, and N. Shibata, Org. Lett, vol.2, issue.5, p.639, 2000.

, Synthesis of (E)-N-benzyl-2-fluoro-5-(triphenylsilyl)pent-3-enamide (68) The title compound was prepared from fluoride 29 following procedure B at 40 °C and purified by column chromatography (cyclohexane/EtOAc, 8:2). Brownish solid (400 mg, 83%)

, HRMS (ESI-): m/z: Calcd for C32H31NO3FSi, pp.1427-1428

, Hz, 1H) ; 4.56 (m, 1H) ; 3.87 (m, 2H) ; 2.13 (q, J = 6.6 Hz, 2H) ; 1.37 (s, 9H) ; 1.341.11 (m, 4H) ; 0.92 (s, 9H) ; 0.82 (t, J = 6.9 Hz, 3H). 13 C NMR (75 MHz, CDCl3) ? 196, Synthesis of (R,E)-tert-butyl (1-((tert-butyldiphenylsilyl)oxy, vol.95, pp.1110-1111, 1167.

, HRMS (ESI + ): m/z: Calcd for C32H48NO4Si, pp.1110-1111, 1167.

, J = 6.5 Hz, 3H). 13 C NMR (75 MHz, CDCl3)

, Synthesis of (R,E)-tert-butyl (1-((tert-butyldiphenylsilyl)oxy)-3-oxononadec-4-en-2chromatography (cyclohexane/EtOAc, 95:5). Brownish oil (114 mg, 76%), HRMS (ESI + ): m/z: Calcd for C38H60NO4Si, vol.4292, p.622, 1428.

, 1H) ; 5.54 (s, J = 7.6 Hz, 1H) ; 4.56 (m, 1H) ; 3.87 (m, 2H) ; 2.12 (q, J = 6.9 Hz, 2H) ; 1.37 (s, 9H) ; 1.35-1.09 (m, 24H) ; 0.93 (s, 9H) ; 0.8 (t, J = 6.2 Hz, 3H). 13 C NMR (75 MHz, CDCl3) ? 196

, The title compound was prepared from amine 82 and fluoride 51 following procedure H and purified by column chromatography (cyclohexane/EtOAc, 9:1). Clear oil (138 mg, 69%), p.25

=. , , vol.4

, Hz, 1H) ; 6.01 (m, 1H) ; 5.6 (dt, J = 15.5, 6.8 Hz, 1H) ; 5.56 (m, 2H) ; 5.22 (dd, J = 48.9, 6.6 Hz, 1H), p.2

J. Hz-;-d and . 11, JC-F = 18.88 Hz), 91.3 (d, JC-F = 184.56 Hz), 36 Hz), 135.7 (d, JC-F = 4.87 Hz), 134.1, 132.5 (d, JC-F = 14.87 Hz), 130.2, 128.9, vol.139, pp.1111-1112, 1465.

, mg, 0.168 mmol, 1 eq, THF. The reaction mixture was cooled down to 0°C and TBAF (1 M in THF, p.1

, Saturated aqueous NH4Cl was then added and the mixture was extracted with EtOAc. Organics were dried over MgSO4 filtered and volatiles were removed under reduced pressure. Purified by column chromatography (cyclohexane/EtOAc, 7:3). White solid (42 mg, 43%). Mp = 88 °C, p.7

, 1H) ; 4 (dd, J = 11.4, 3.3 Hz, 1H), 3.91 (dd, J = 7.3, 3.5 Hz, 1H) ; 3.72 (dd, J = 11.4, 3.1 Hz, 1H) ; 2.70 (brs, 2H) ; 2.08 (m, 4H) ; 1.52-1.10 (m, 46H) ; 0.88 (t, J = 6.4 Hz, 6H). 13 C NMR (75 MHz, CDCl3) ? 169.5 ppm (d, J = 19.8), 139.2 (J = 11

, Rf = 0.28 (cyclohexane/EtOAc, 9:1). 1 H NMR (300 MHz, CDCl3) ? 7.69 ppm

J. Hz-;-d and J. =. =-;-d, HRMS (ESI + ): m/z: Calcd for C39H66NO4Si, vol.129, p.3, 1169.

, Rf = 0.24 (cyclohexane/EtOAc, 8:2). 1 H NMR (300 MHz, CDCl3) ? 7.67 ppm (m, 4H); 7.41 (m, 6H); 3.73 (m, 2H); 3.58 (m, 1H); 2.92 (br.s, 1H); 2.12 (br.s, 2H); 1.55-1.23 (m, 26H); 1.09 (s, 9H); 0.90 (t, J = 5.9 Hz, 3H). 13 C NMR (75 MHz, CDCl3), 25 = +7.3 (c 0.7, CHCl3), vol.8

, Synthesis of (E)-N-benzyl-2-fluorooctadec-3-enamide (91)

, The title compound was prepared from fluoride 51 or 57 following procedure H and purified by column chromatography (cyclohexane/EtOAc, vol.9

, 25 = +16.25 (c 1, CHCl3). 1 H NMR (300 MHz, CDCl3) ? 7.24 ppm, vol.9

. Hz,

3. Hz, 13 C NMR (75 MHz, CDCl3) ? 168.8 ppm (d, JC-F = 20.98 Hz), vol.138

J. Hz-;-d and . 18, HRMS (ESI + ): m/z: Calcd for C25H40NOFNa, vol.87, pp.1026-1027, 1651.

, Chapitre III : ?-aminocarbonyles ?,? insaturés Synthesis of (E)-N

, The title compound was prepared from fluoride 55 following procedure I and purified by column chromatography (CH2Cl2/MeOH 95:5). White solid (147 mg, 95%). Mp = 131 °C

, Hz, 2H), 3.70 (d, J = 13.1, 1H), 3.53 (d, J = 13.1, 1H), 3.09 (m, 1H), 1.69 (m, 1H), 1.16 (m, 2H), 1.22 (m, 4H), 0.82 (t, J = 6.7, 3H). 13 C NMR (75 MHz, CDCl3) ? 165.6,161.9 ppm (d, J C-F = 244.7 Hz), p.282

. Mhz, , vol.1220, p.3281, 1508.

, HRMS (ESI + ): m/z: Calcd for C22H28N2OF

, The title compound was prepared from fluoride 55 following procedure I and purified by column chromatography (CH2Cl2/MeOH 9:1), Mp = 82 °C. Rf = 0.25 (CH2Cl2/MeOH 9:1). 1 H NMR (300 MHz, CDCl3) ? 7.19 ppm

. Hz,

C. Nmr, 75 MHz, CDCl3) ? 165.6 ppm, 145.9, pp.986-987, 1536.

, HRMS (ESI + ): m/z: Calcd for C16H25N2O, p.261, 1960.

, 3.13 (m, 2H), 2.87 (m, 1H), 2.57 (m, 4H), 1.72 (m, 4H), 1.46 (m, 1H), 1.11 (m, 5H), 0.81 (2t, J = 6.3, 3H). 13 C NMR (75 MHz, CDCl3), pp.1210-1211, 1538.

, Synthesis of (2S)-methyl 2-((E)-4-(isopropylamino)oct-2-enamido)-(EtOAc), HRMS(ESI + ): m/z: Calcd for C22H33N2O3 [M+H] + : 373.2491 found: 373.2489

. Mhz, , pp.3-6

. Hz, 66 (s, 3H), 3.19 (m, 1H); 3.08 (m, 2H), 2.75 (m, 1H); 1.59-1.09 (m, 6H); 0.96 (m, 6H); 0.81 (m, 3H). 13 C NMR (75 MHz, CDCl3) ? 172, vol.3, p.3288, 1211.

, The title compound was prepared from fluoride 49 following procedure I and purified by column chromatography (CH2Cl2/EtOAc, 5:5 to CH2Cl2, White solid, vol.9

, Rf = 0.30 (CH 2 Cl 2 /MeOH 9:1). 1 H NMR (300 MHz, CDCl3) ? 7.20-6.99 ppm (m, 10H), vol.6

, )-4-(methylamino)oct-2-enamido)-3-phenylpropanoate (102) The title compound was prepared from fluoride 49 following procedure I at 40 °C and purified by column chromatography, HRMS (ESI + ): m/z: Calcd for C26H35N2O3, pp.1209-1210, 1367.

, Mp = 73 °C. 1 H NMR (300 MHz, CDCl3) ? 7.22-7.01 ppm (m, 5H), 6.53 (dd, J = 15.3, 7.8 Hz, 1H), 6.14 (d, J = 7.7 Hz, 1H, NH), vol.5, pp.19-28, 1538.

, Synthesis of (2S)-methyl 4-methyl-2-((E)-4-morpholinooct-2-enamido)pentanoate (103) The title compound was prepared from fluoride 52 following procedure I and purified by column chromatography, HRMS (ESI + ): m/z: Calcd for C19H29N2O3 [M+H] + : 333.2178 found: 333.2188, pp.1212-1213

. Chcl3, Rf = 0.32 (CH2Cl2/EtOAc, 5:5). 1 H NMR (300 MHz, CDCl3) ? 6.73 ppm (dd, J = 15.3, 8.9 Hz, 1H), 6.03 (d, J = 7.5, Hz, 1H, NH), vol.5, p.3306, 1120.

, Synthesis of (E)-4-morpholino-N-(4-(trifluoromethyl)phenyl)oct-2-enamide (104)

, The title compound was prepared from fluoride 53 following procedure I and purified by column chromatography (CH2Cl2/MeOH 9:1). White solid (112 mg, 87%)

, Cl 2 /MeOH 9:1) 1 H NMR (300 MHz, CDCl3) ? 7.58 ppm, ((AB system, J AB =, vol.8, issue.2

, Synthesis of (E)-2-morpholino-N-(4-(trifluoromethyl)phenyl)purified by column chromatography, HRMS (ESI + ): m/z: Calcd for C19H26N2O2F3, p.371, 1946.

, Rf = 0.31 (CH2Cl2/AcOEt, 5:5). 1 H NMR (300 MHz, CDCl3) ? 9.04 ppm (s, 1H) ; 7.56, ((AB system J AB = 8.69 Hz

, C19H25F3N2O2 370.41 g.mol-1 (m, 1H), 2.52-2.48 (m, 4H), 1.67 (m, 1H), p.371, 1320.

, HRMS (ESI +, pp.1118-1119, 1609.

, The title compound was prepared from fluoride 54 following procedure I and purified by column chromatography (CH2Cl2:MeOH, 85/15)

, 84 (dia A) (d, J = 15.5 Hz, 0.5H) and 5.71 (dia B) (d, J = 15.4 Hz, 0.5H), 3.80 (dia A) (q, J = 6.5Hz, 0.5H) and 3.73 (dia B) (q, J = 6, 5H) and 6.49 (dia B) (dd, J = 14.5, 8.5 Hz, 0.5H), 6.52 (dia A+B) (brs, 1H, NH amide), 5.97 (dia A+B) (brs, 1H, NH amide), vol.5

, HRMS (ESI + ): m/z: Calcd for C16H25N2O, p.261, 1602.

, CH2Cl2/MeOH, 95:5). 1 H NMR (300 MHz, CDCl3) ? for two dia A+B 8.14 and 7.84 ppm (2s, 1H, NHAr), 7.65-7.44 (m, 4H), 7.21-7.13 (m, 5H), vol.6

, 93 (dia A) (d, J = 15.5 Hz, 0.5H) and 5.84 (dia B) (d, J = 15.4 Hz, 0.5H), 3.75 (dia A) (q, J = 6.5Hz, 0.5H) and 3.65 (dia B) (q, J = 6, 5H) and 6.57 (dia B) (dd, J = 14.5, 8.5 Hz, 0.5H), vol.5

, HRMS (ESI +, pp.1066-1067, 1112.

, The title compound was prepared from fluoride 44 following procedure I and purified by column chromatography (CH2Cl2/MeOH, 95:5). White solid (94 mg, 80%). Mp = 46 °C, p.25

=. , 08 (c 1.2 CHCl 3 ). Rf = 0.55 (CH 2 Cl 2 /MeOH, 95:5). 1 H NMR (300 MHz, CDCl3) ? 7, p.28

, Hz, 6H), 0.86 (t, J = 6.8 Hz, 3H). 13 C NMR (75 MHz, CDCl3) ? 175, p.3319, 1198.

, The title compound was prepared from fluoride 53 following procedure I and purified by column chromatography (CH2Cl2/MeOH 9:1). Clear oil (225 mg, 80%)

, 74 (dia A) (dd, J = 15.2, 8.6 Hz, 0.5H) and 6.64 (dia B) (dd, J = 15.4, 8.5 Hz, 0.5H), 6.05 (dia A) (d, J = 15.2 Hz, 0.5H) and 5.96 (dia B) (d, J = 15, CH2Cl2/MeOH 9:1). 1 H NMR (300 MHz, CDCl3) ? 7.81-7.55 ppm (m, 4H Ar + 1H NH Ar), vol.6

, HRMS (ESI + ): m/z: Calcd for C21H30N2O3F3

, (R)-1-phenylethyl)pyrrolidin-2-yl)acrylamide (117) The title compound was prepared from fluoride 116 following procedure I and purified by column chromatography, 3309, 2928, 1681 cm-1. HRMS (ESI + ): m/z: Calcd for C15H22N2OF

, CH2Cl2/EtOAc, 5:5). 1 H NMR (300 MHz, CDCl3) ? 7.19 ppm

. Hz, MHz, CDCl3) ? 168.47 ppm

, HRMS (ESI + ): m/z: Calcd for C15H21N2O

, 5.24 and 5.08 (dd, J = 49.1, 6.8 Hz, 1H), 3.73 (q, J = 6.5Hz, 1H), 2.50-2.35 (m, 2H), 2.29-2.07 (m, 2H), 1.59 (brs, 1H, NH), 1.42 (m, 4H), 1.34 (d, J = 6.7Hz, 3H). 13 C NMR (75 MHz, CDCl3), NMR (300 MHz, CDCl3) ? 7.34-7.22 ppm (m, 5H), 6.47 (brs, 1H), 6.34 (brs, 1H), 5.94 (m, 1H), 5.55 (m, 1H), pp.1130-1131, 1177.

, Oil (198 mg, 77%). 1 H NMR (300 MHz, CDCl3) ? 7, HRMS (ESI + ): m/z: Calcd for C16H24N2OF [M+H] + : 279.1873 found: 279.1866. chromatography (CH2Cl2/MeOH, vol.10

C. Nmr,

/. Ch2cl2 and . Meoh, 31 Hz, 1H); 7.53 ppm (dd, J = 6.15, 3.31 Hz, 1H) ; 5.70 ppm (m, 1H) ; 5.34 (m, 1H) ; 4.93 (dd, J = 49.67, 6.89 Hz, 1H) ; 2.57 (t, J = 7.3 Hz, 2H) ; 1.84 (m, 2H) ; 1.33 (m, 2H) ; 1.14 (m, 4H), and 2% Et3N). White solid (360 mg, 67%). Rf = 0.13 (CH2Cl2/MeOH, 8:2 and 2% Et3N). 1 H NMR (300 MHz, CDCl3) ? 7.97 ppm (dd, J = 6, vol.8

, Rf = 0.15 (CH2Cl2/MeOH 1:1). 1 H NMR (300 MHz, CDCl3) ? 6.82 ppm (dd, J = 15.4, 59. Hz, 1H) ; 6.13 (br.s, 1H), The title compound was prepared from fluoride 127 following procedure I and purified by column chromatography (EtOAc)

, HRMS (ESI + ): m/z: Calcd for C9H17N2O

, 20 mmol, 4 eq.) in diethyl ether (1 M) was added 5-Bromopent-1-en (2.027, 17.10 mmol, 2 eq.). the reaction was allowed to warm up to rt and stirred for 1 hour. The stirring was then stopped and after 30 min, liquid layer was added via syringe dropwise onto a solution of sulfinimide, vol.34

, Upon completion, the reaction was warmed up to r.t., sat. NH4Cl was added and the aqueous layer was extracted 3 times with CH2Cl2. organic layers were gathered, dried over MgSO4, filtered and volatiles were removed under reduced pressure. Crude mixture was purified by column chromatography (cyclohexane/EtOAc, 8:2) Clear oil (1.84 g, 88%), CH2Cl2 (5 M) at-55 °C. The reaction was then warmed up to-10 °C and stirred for 4 h

, 1H); 1.99 (q, J = 6.8 Hz, 2H); 1.56-1.24 (m, 8H); 1.14 (s, 9H); 0.83 (t, HRMS (ESI + ): m/z: Calcd, pp.1049-1050, 2869.

, Rf = 0.15 (CH2Cl2/EtOAc, 5:5). 1 H NMR (300 MHz, CDCl3) ? 6.73 ppm (m, 1H), The title compound was prepared from fluoride 25 following procedure B at 40 °C and purified by column chromatography (CH2Cl2/EtOAc, 5:5 then CH2Cl2/MeOH, vol.9

, Hz

, HRMS (ESI + ): m/z: Calcd for C15H30N2O2SF, p.321, 1682.

, To a flask containing fluoride 131 (160 mg, 0.50 mmol, 1 eq.diethylether and filtered yielding compound 133 (120 mg, 0.47 mmol, 95%), clear oil

, 1 H NMR (300 MHz, CDCl3) ? 6.67 ppm (br.s, 1H); 6.49 (br.s, 1H); 5.97 (m, 1H), vol.8

, 91 Hz), 138.4 (dd, J = 11, 1.1 Hz), vol.122

. Hz,

, HRMS (ESI + ): m/z: Calcd for C11H22N2OF, pp.1679-1680, 2872.

, The title compound was prepared from fluoride 133 following procedure I and purified by column chromatography (EtOAc)

. Mhz, 1H); 6.30 (br.s, 1H); 6.17 (br.s, 1H); 6.07 (d, J = 15.7 Hz, 1H); 4.06 (br.s, 1H); 3.37 (m, 1H); 2.65 (m, 1H); 1.93-1.68 (m, 3H), vol.1, p.1397, 1608.

, Une réaction de fluoration électrophile d'allylsilanes a été développé afin d'accéder à des motifs ?fluroénamides hautement fonctionnalisés. Ces ?-fluroénamides peuvent être de types variés : benzylamines, anilines, ou alkyles? Un accent particulier a été mis sur des dérivés d'acides aminés pouvant ainsi servir de peptido-mimétiques

S. Dans-un, accéder à une plus grande variété moléculaire, la réactivité de ces motifs fluorés allyliques vis-à-vis des réactions de métathèses croisées, très peu étudiée, a été investiguée. La faisabilité de ces deux méthodologies a été démontrée par la synthèse d'une molécule cible originale

L. Fluor, Une réaction d'amination catalytiques sur les dérivés ?-fluroénamides fonctionnalisés a été développée, permettant l'incorporation de nucléophiles aminés variés. Cette réaction permet de produire des motifs ?-aminomides-?,?-insaturés, principalement utilisé pour ses propriétés physico-chimiques et pharmacocinétiques a ici pu être exploité pour sa réactivité

, Mots-clés: fluorure allylique, fluoration éléctrophile, métathèse croisée, amination