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, Low actinic glassware and aluminium film were used for all experiments involving compounds bearing the nitroveratryl moiety. Column chromatography (CC): silica gel 60
, Merck silica gel 60 F-254 precoated plates; detection by UV (254 and 365 nm). 1 H NMR spectra were recorded at 300 MHz. 13 C NMR spectra were recorded at 75 MHz with complete proton decoupling; chemical shifts (?) in ppm related to protonated solvent as internal reference ( 1 H: CHCl3 in CDCl3, 7.26 ppm, vol.13
, 13 C: 13 CD3 13 CN in CD3CN)
, Coupling constants J in Hz; current notations are used for multiplicity (s: singlet; bs: broad singlet
, Cyclisation series A. 2-HPC 2-(methylamino)-4-nitrophenol (1)
, 5 mL of dry MeOH under inert atmosphere and in an ice bath were added iodomethane (330 µL, 5.23 mmoles, 1.6 eq.) and triethylamine (750 µL, 5.56 mmoles, 1.7 eq.). The reaction was then heated to 40°C and stirred 3h at room temperature. 330 µL of iodomethane and 750 µL of triethylamine were added again and the solution was stirred 1h more. The solution was concentrated in vacuo and then extracted by K2CO3(aq). The aqueous phase was reacidified by HCl(aq) 1M to pH 7 and extracted by EtOAc; the resulting organic phase was washed by distilled water and brine. The organic phase was dried on MgSO4, vol.3
, ?H (CDCl3) 2.94 (s, 3H), 6.73 (d, 1H, J = 8.5 Hz), vol.7
,
, mmoles, 1 eq.) in 9 mL of dry DMF under inert atmosphere were added iodomethane (203 µL, 3.89 mmoles, 1.2 eq.) and sodium hydrogenocarbonate (326.8 mg, 3.89 mmoles, 1.2 eq.). The reaction was stirred overnight at room temperature. The solution was concentrated in vacuo and then extracted by K2CO3(aq). The aqueous phase was reacidified by HCl(aq) 1M to pH 7 and extracted by EtOAc; the resulting organic phase was washed by distilled water and brine. The organic phase was dried on MgSO4
, ?H (CDCl3) 2.94 (s, 3H), 6.73 (d, 1H, J = 8.5 Hz), vol.7
,
, 5-dimethoxy-2-nitrobenzyl)oxy)-N-methyl-5-nitroaniline
, A solution of I-A-4 (50 mg, 0.11 mmoles, 1 eq.) in 3 mL of a blend of TFA/DCM (1:1) was stirred 2h at room temperature. The mixture was then treated by K2CO3(aq), water and brine, dried on MgSO4, filtered and concentrated under reduced pressure. The product was obtained without purification as a yellow solid
, Rf = 0.11 (40% EtOAc/Cx)
, 77 (s, 1H). ?c (CDCl3), 7.04 (s, 1H), 7.42 (d, 1H, J = 3 Hz), 7.57 (dd, 1H, J = 3/8.8 Hz), vol.7
, 67 mmoles, 1 eq.) in 15mL of toluene were added 3.3-dimethylacrylic acid (367.4 mg, 3.67 mmoles, 1 eq.) and methanesulfonic acid (1.76 g, 18.35 mmoles, 5 eq.). The mixture was heated to 85°C and stirred under argon for 5h and then allowed to cool down to room temperature. The solution was diluted by EtOAc treated by K2CO3(aq), distilled water and brine, dried on MgSO4, filtrated and evaporated under reduced pressure. The residue was finally purified by column chromatography
, To a solution of I-B-1 (630 mg, 2.89 mmol, 1 eq, anhydrous THF (10 mL) in an ice bath was added lithium aluminium hydride (109.7 mg, vol.2, p.89
, °C, and then the suspension was filtered on Celite 535; the resulting filtrate was diluted with EtOAc and treated with 1 M HCl, water and brine; and finally dried on MgSO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel
, Rf = 0.45 (30% EtOAc/Cx)
, )oxy)-2-methylbutan-2-yl, vol.5, p.6
, 7 mL of dry DCM were added tert-Butyldimethylsilyl chloride (265.3 mg, 1.76 mmoles, 1.1 eq.), triethylamine (280 µL, 2.08 mmoles, 1.3 eq.) and a catalytic amount of dimethylaminopyridine. The mixture was stirred overnight at room temperature and then treated by NH4Cl(aq), distilled water and brine. The organic phase was dried on MgSO4, The residue was purified on silica gel
, allyloxy)methyl)-4-nitrobenzene
, g, 32.7 mmoles, 1 eq.). Then, allyl bromide (3.4 mL, 38.2 mmoles, 1.2 eq.) was injected and the resulting suspension was allowed to be warmed to room temperature and stirred overnight. The green suspension was neutralised by NH4Cl(aq), diluted by EtOAc and treated by water and brine. The organic phase was dried by MgSO4, vol.1
, Rf = 0.28 (15% EtOAc/Cx)
, allyloxy)methyl)aniline
, 10 mL of ethanol/water (95:5) was added tin(II) chloride (6.13 g, 32.32 mmoles, 5.5 eq.) under inert atmosphere. The solution was then heated to 70°C for 1h. The resulting mixture was diluted by EtOAc and tin salts were neutralised by a concentrated aqueous solution of K2CO3 and filtrated, The aqueous layer was removed and the organic phase was washed with water and brine. After drying on MgSO4, filtration and evaporation, the residue was purified on silica gel, vol.10, p.30
, EtOAc/Cx) to give the product as a dark solid (580 mg, 61%)
, , vol.27
, Bis-carbonylation of the nitrogen, vol.4
, 463 mmoles, 1 eq.) in 5 mL of dry THF was added 4.5-dimethoxy-2-nitrobenzyl chloroformate (127 mg, 0.463 mmoles, 1 eq.), triethylamine (321 µL, 2.315 mmoles, 5 eq.) and DMAP (catalytic amount). The resulting solution was stirred under argon overnight at room temperature. The organic phase was diluted by DCM and washed by NH4Cl(aq), distilled water and brine. Then, it was dried on MgSO4
, mg, 1.26 mmoles, 1 eq.) in 5 mL of dry THF were injected acetyl chloride (90 µL, 1.26 mmoles, 1 eq.) and pyridine (153 µL, 1.89 mmoles, 1.5 eq.). The resulting suspension was stirred 1h at room temperature and treated by K2CO3(aq), HCl 1M, distilled water and brine
, , vol.27
, mmoles, 1 eq.) in 6.5 mL of dry THF cooled by an ice bath was injected under argon lithium diisopropylamide 2M in hexane (575 µL, 1.15 mmoles, 1 eq.) before acetyl chloride (82 uL, 1.15 mmoles, 1 eq.) was added. The solution began immediately orange and the ice bath was removed as the solution was allowed to warm up and be stirred overnight at room temperature. The mixture was then diluted by EtOAc and treated by NH4Cl(aq), water and brine
, mmoles, 1 eq.) in 6.5 mL of dry THF, cooled to 0°C by an ice bath, was injected lithium diisopropylamide 2M in hexane (575 µL, 1.15 mmoles, 1 eq.) under argon. After 5 min under stirring, 4.5-dimethoxy-2-nitrobenzyl chloroformate (316.6 mg, 1.15 mmoles, 1 eq.) was added. The solution was stirred overnight before being neutralised by NH4Cl(aq), diluted by EtOAc and treated by distilled water and brine. The organic phase was dried on MgSO4, The residue was finally purified on silica gel
, 5-dimethoxy-2-nitrobenzyl acetyl(4-(hydroxymethyl)phenyl)carbamate (18)
, 3 mg, 0.67 mmoles) in 10 mL of dry MeOH/DCM (1:1) was added 100 mg of Amberlyst 15. The suspension was vigorously stirred overnight and then filtrated. The solvent was evaporated and the residue was purified by column chromatography, vol.345, p.30
, EtOAc/Cx) to give the product as a white solid (212 mg, 78%)
, Rf = 0.12 (40% EtOAc/Cx)
, -(((tert-butyldimethylsilyl)oxy)methyl)aniline (19)
, ) was dissolved in 4 mL of dry THF and put under argon before triethylamine (630 µL, 3.525 mmoles, 5 eq.) and methyl chloroformate (54 µL, 0.705 mmoles, 1 eq.) were injected. The solution turned red immediately and was stirred 30min before being diluted by EtOAc and treated by NH4Cl(aq), water and brine
, 7.36 (d, 2H, J = 9 Hz)
, 3 mg, 0.353 mmoles, 1 eq.) in 2 mL of dry THF were successively injected at 0°C lithium diisopropylamide 1M in THF (352 µL, 0.353 mmoles, 1 eq.) and methyl chloroformate (27 µL, 0.353 mmoles, 1 eq.). The resulting dark solution was stirred 1h, diluted by DCM and then treated by NH4Cl(aq), distilled water and brine. After filtration and concentration, the crude mixture was purified on silica gel, vol.104
, -tertbutyldimethylsilyl)oxy)phenyl)biscarbamate (21)
, mmoles, 1 eq.) in 3 mL of dry THF were successively injected at 0°C lithium diisopropylamide 1M in THF (568 µL, 0.568 mmoles, 1 eq.) and 4.5-dimethoxy-2-nitrobenzyl chloroformate (156.6 mg, 0.568 mmoles, 1 eq.). The resulting dark solution was stirred overnight, diluted by DCM and then treated by NH4Cl(aq), distilled water and brine. After filtration and concentration, the crude mixture was purified on silica gel
, Bis-amides 1. Acylation of protected 4-aminobenzyl alcohol N-(4-((allyloxy)methyl)phenyl)-4-chlorobutanamide (22)
, 3 mL of dry THF were successively injected triethylamine (721 µL, 5.20 mmoles, 5 eq.) and 4-chlorobutyryl chloride (117 µL, 1.04 mmoles, 1 eq.). The mixture was stirred 30 min before being diluted by DCM and treated by K2CO3(aq), NH4Cl(aq), distilled water and brine. The organic phase was dried on MgSO4
, 39 (t, 2H, J = 6/15 Hz), 3.68 (t, 2H, J = 6/15 Hz, ?H (CDCl3) 1.95 (m, 2H), vol.2
, 7.61 (d, 2H, J = 9 Hz)
, mmoles, 1 eq.) in 2 mL of dry THF were successively injected triethylamine (388 µL, 2.80 mmoles, 5 eq.) and 4-chlorobutyryl chloride (63 µL, 0.56 mmoles, 1 eq.). The mixture was stirred 45 min before being diluted by DCM and treated by K2CO3(aq), NH4Cl(aq), distilled water and brine. The organic phase was dried on MgSO4
, Rf = 0.28 (20% EtOAc/Cx) ?H (CDCl3) 1.19 (s, 9H), 1.95 (m, 2H), vol.2
, tert-butyldimethylsilyl)oxy)methyl)phenyl)-4-chlorobutanamide (24)
, mmoles, 1 eq.) in 5 mL of dry THF were successively injected triethylamine (320 µL, 2.32 mmoles, 5 eq.) and 4-chlorobutyryl chloride (52 µL, 0.463 mmoles, 1 eq.). The mixture was stirred 30 min before being diluted by DCM and treated by K2CO3(aq), NH4Cl(aq), distilled water and brine. The organic phase was dried on MgSO4
, (tertof II-A-5 (110 mg, 0.463 mmoles, 1 eq.) in 5 mL of dry THF at 0°C were successively added K2CO3 (320.6 mg, 2.32 mmoles, 5 eq.) and 4-bromobutyryl chloride (54 µL, 0.463 mmoles, 1 eq.). The mixture was stirred 2h min before being diluted by DCM and treated by NH4Cl(aq), distilled water and brine, 5.05 (s, 2H), 7.34 (d, 2H, J = 9 HZ), 7.61 (d, 2H, J = 9Hz
, 5.05 (s, 2H), 7.34 (d, 2H, J = 9 Hz), 7.61 (d, 2H, J = 9 Hz)
, Amination of alkyl chains 1-(4,5-dimethoxy-2-nitrophenyl)-Nmethylmethanamine (26)
, mL, excess) was slowly added. The mixture was stirred 4h and then diluted (EtOAc) and washed with water. The aqueous layer was extracted several time with EtOAc. The combined organic phase was then acidified by HCl 2M. The resulting acid aqueous layer was finally basified by NaOH (5% in water) and extracted by EtOAc. The organic layer was washed by water and brine, dried on MgSO4, 5-dimethoxy-2-nitrobenzyl bromide (500 mg, 1.811 mmoles, 1 eq.) was dissolved in THF and methylamine 40% in water
, Rf = 0.10 (40% EtOAc/Cx)
, 61 (s, 1H). methyl 4-((4,5-dimethoxy-2-of II-B-5 (70 mg, 0.309 mmoles, 1 eq.) in 2 mL of dry THF was added potassium iodide (catalytic amount) and were injected under inert atmosphere triethylamine (214 µL, 1.545 mmoles, 5 eq.) and methyl 4-bromobutyrate (117 µL, 0.928 mmoles, 3 eq.). The solution was vigorously stirred overnight, then diluted by EtOAc and treated by water and brine, After drying and concentration, the residue was purified on silica gel, vol.7
, Rf = 0.15 (40% EtOAc/Cx)
, 17 (s, 3H), 2.28 (t, 2H, J = 6/15 Hz), 2.38 (t, 2H, J = 6/15 Hz, ?H (CDCl3) 1.74 (m, 2H), vol.2
, (tert-butyldimethylsilyl)oxy)methyl)phenyl) carbamate (28, -carbamates allyl, p.4
, 1 eq.) in 5mL of dry THF under inert atmosphere and in an ice bath were injected N,N-Diisopropylethylamine (1.8 mL, 10.53 mmoles, 5 eq.) and allyl chloroformate (1.12 mL, 10.53 mmoles, 5 eq.). The bath was removed as precipitation of salts and discoloration of the red solution was observed. After 1h30, the reaction was quenched with an aqueous NH4Cl solution and the mixture was diluted with DCM. The organic phase was then washed with water and brine
, After the base was completely dissolved, 4.5-dimethoxy-2-nitrobenzyl chloroformate (403.2 mg, 1.463 mmoles, 1 eq.) was added. The resulting solution was allowed to come back very slowly at room temperature by letting dry ice sublimate and stirred overnight. The organic phase was diluted by DCM, treated by NH4Cl/water/brine, dried on MgSO4 and evaporated. The resulting powder was purified on silica gel
, Rf = 0.47 (30% EtOAc/Cx)
, N-allyl-N-4,5-dimethoxy-2-nitrobenzyl (4-(hydroxymethyl)phenyl)biscarbamate (30)
, 855 mmoles) was first dissolved in 4mL of DCM and then dry MeOH (4mL) and Amberlyst®15 were added. The suspension was stirred overnight, filtrated and washed several time with acetone. The resulting solution was concentrated and purified
, Rf = 0.11 (40% EtOAc/Cx)
, mmoles, 1 eq.) in 2 mL of dry DMF was added N,N-Diisopropylethylamine (435 µL, 2.565 mmoles, 5 eq.) under argon. The solution was then cooled by an ice bath and methanesulfonyl chloride (200 µL, 2.565 mmoles, 5 eq.) was injected. The mixture was heated to 85°C for 2h before being allowed to cool down to room temperature. The organic phase was diluted by DCM and washed with NH4Cl/water/brine, dried and concentrated
, Rf = 0.21 (30% EtOAc/Cx)
, 5.12 (d, 1H, J= 3 Hz), 5.60 (s, 2H), 5.76 (m, 1H), 6.98 (s, 1H), 7.19 (d, 2H, J = 9 Hz), vol.7
, HRMS, calculated: m/z 465.0986, found: m/z 487.0879
, 1 eq.) was dissolved in 5mL of distilled acetone and heated to reflux before sodium iodide (564 mg, 3.765 mmoles, 10 eq.) was added. After 2h, the solution was diluted by DCM and washed with water and brine. The organic layer was dried and concentrated before being purified on silica gel
, Rf = 0.21 (30% EtOAc/Cx)
, 5.17 (dd, 1H, J= 3/9 Hz), 5.65 (s, 2H), 5.82 (m, 1H), 7.11 (s, 1H), 7.18 (d, 2H, J = 6 Hz), vol.7
, 1 eq.) was dissolved in 5mL of dry acetonitrile and put under inert atmosphere before 7-hydroxy-4-trifluoromethylcoumarin (187.6 mg, 0.815 mmoles, 2.5 eq.) and silver(I) oxide (377.7 mg, 1.630 mmoles, 5 eq.) were added. The suspension was stirred overnight, then filtrated on celite and washed several times with DCM. The resulting organic solution was treated by an aqueous solution of NaHCO3, then water and brine, p.40
, 45%) as an off-white solid. For physical chemistry experiments, another purification was done by HPLC using 80 to 90% gradient of CH3CN/water/0.1% TFA, Waters XBridge® Prep C18 5µm OBD? 30 x 150mm Column, the ether 28 was obtained (96.7 mg
, Rf = 0.29 (40% EtOAc/Cx)
, 10 (s, 2H), 5.60 (s, 2H), 5.76 (m, 1H), 6.56 (s, 1H), 6.88 (d, 1H, J = 3 Hz), 6.93 (dd, 1H, J = 3/9 Hz), 7.07 (s, 1H), 7.23 (d, 2H, J = 9 Hz), 7.43 (d, 2H, J = 9 Hz), 7.59 (dd, 1H, J = 3/9 Hz), vol.5
, :1) before palladium (II) acetate (0.1 mg, 0.0004 mmoles, 2 moles%), triphenylphosphine m-trisulfonate (0.4 mg, 0.0008 mmoles, 4 moles%) and diethylamine (4 µL, 0.04 mmoles, 2.2 eq.) were added. The solution was stirred 1h, then diluted by DCM and treated by water and brine. After drying on MgSO4, evaporation and purification on silica gel (0 to 100% DCM/EtOAc), the monocarbamate 28 was obtained (9.3 mg, 91%) as an slightly yellow solid. For physical chemistry experiments, Compound II-C-6 (12 mg, 0.018 mmoles, 1 eq.) was dissolved in 5mL of a blend of acetonitrile and water, vol.4
, Rf = 0.29 (40% EtOAc/Cx)
, 04 (s, 2H), 5.53 (s, 2H), 6.55 (s, 1H), 6.76 (bs, 1H), 6.86 (d, 1H, vol.5
, -oxo-4-(trifluoromethyl)-2H-chromen-7-yl)oxy)methyl)phenyl)carbamate (35), p.4
, After no more starting material was observed by TLC, the solution was diluted by DCM and then washed by water and brine. After drying on MgSO4, evaporation and purification on silica gel (0 to 40% EtOAc/Cx), the mono carbamate 28 was obtained (13 mg, 86%) as an off-white solid. For physical chemistry experiments, another purification was done by HPLC using 80 to 90%, Compound II-C-6 (23 mg, 0.035 mmoles, 1 eq.) was dissolved in 20mL of a blend of acetonitrile and water, vol.4
, Rf = 0.29 (40% EtOAc/Cx)
, 91 (s, 2H), 5.02 (dd, 1H, J = 3/12 Hz), 5.14 (dd, 1H, J = 3/18 Hz), 5.77 (m,1H), 6.44 (s, 1H), 6.80 (dd, 2H, J = 3/9 Hz), 7.18 (d, 2H, J = 9 Hz), 7.27 (d, 2H, J = 9 Hz), vol.4
, Tri-branched phenols A
, ) was dissolved in 1 mL of dry THF and put under argon in an ice bath. Then triethylamine (450 µL, 3.244 mmoles, 5 eq.) and acetyl chloride (230 µL, 3.244 mmoles, 5 eq.) were injected. A precipitate of triethylammonium chloride appeared instantly and the reaction was quenched by introduction of NH4Cl(aq). The organic phase was diluted by EtOAc and washed by water and brine. The EtOAc solution was dried on MgSO4
, -(hydroxymethyl)benzene-1,3,5-triyl triacetate (37)
, 1 eq.) was dissolved in dry MeOH (1 mL) and put in an ice bath before sodium borohydride (36.8 mg, 0.974 mmoles, 1.5 eq.) was introduced. After 15 min of stirring, NH4Cl(aq) was injected carefully. The solution was diluted by EtOAc and washed several time with water and brine. The organic phase was then dried on MgSO4
, Rf = 0.19 (40% EtOAc/Cx)
, (tert-butyldimethylsilyl)oxy)methyl)benzene-1,3,5-triyl triacetate (38, p.2
, 1 eq.) in solution in 2 mL of dry DCM was strirred under argon and then tert-Butyldimethylsilyl chloride (97 mg, 0.649 mmoles, 1 eq.) and imidazole (53 mg, 0.779 mmoles, 1.2 eq.) were added. The resulting suspension was stirred vigorously for 3h. The organic phase was washed by water and brine, dried on MgSO4, filtrated and evaporated. The residue was finally purified by column chromatography, Alcohol
, 3-dithian-2-yl)benzene-1,3,5-triyl triacetate (39)
, mg, 1.298 mmoles, 1 eq.) in 5 mL of DCM was introduced I2 (33 mg, 0.13 mmoles, 0.1 eq.). The resulting solution was stirred at room temperature before 1.3-propanedithiol (140 µL, 1.428 mmoles, 1.1 eq.) was injected under argon. After 1h30 min of stirring, the reaction was quenched by Na2S2O3(aq) and treated by water and brine. The organic phase was dried on MgSO4, The crude residue was purified on silica gel
, Rf = 0.48 (30% EtOAc/Cx)
, 34 (s, 6H), 2.46 (m, 4H), 2.63 (s, 3H), 4.89 (s, 1H), 6.87 (s, 2H). 2-(1,3-dithian-2-yl)benzene-1, ?H (CDCl3) 2.03 (m, 2H), vol.2, p.5
, 1 eq.) was dissolved in a suspension of K2CO3 in dry MeOH (5 mL) and stirred 2h at room temperature. The solution was then acidified by NH4Cl and diluted by EtOAc. The organic phase was washed by water and brine, dried on MgSO4, filtrated and concentrated under vacuum. The triphenol was finally purified by column chromatography, Dithiane III-A-4 (480 mg, 1.298 mmoles
, Rf = 0.30 (40% EtOAc/Cx)
, Ether derivatives of phenols 2,4,6-tris(benzyloxy)benzaldehyde (41)
, ) was dissolved in 10 mL of dry DMF before potassium iodide (catalytic quantity) and cesium carbonate (2.1 g, 6.424 mmoles, 3.3 eq.) were added. The mixture was stirred under argon and heated to 80°C as benzyl bromide (763 µL, 6.424 mmoles, 3.3 eq.) was injected. The solution was stirred 48h more, diluted by DCM, and treated successively by an aqueous solution of NaOH (5%), water and brine, The organic phase was dried on MgSO4
, Rf = 0.51 (30% EtOAc/Cx)
, ?H (CDCl3) 5.07 (s, 2H), 5.15 (s, 4H), vol.6
, 649 mmoles, 1 eq.) in 2 mL of dry DMF were added cesium carbonate (697.6 mg, 2.141 mmoles, 3.3 eq.) and allyl bromide (185 µL, 2.141 mmoles, 3.3 eq.). The suspension was vigorously stirred overnight at room temperature and then diluted by DCM. The resulting organic phase was treated by NH4Cl(aq), water and brine, dried on MgSO4, The crude residue was purified on silica gel
,
, ,4,6-tris(allyloxy)phenyl)methanol (43)
, Sodium borohydride (23.8 mg, 0.630 mmoles, 1.5 eq.) was added portion wise. The ice bath was removed and the suspension was allowed to be stirred at room temperature for 1h. The excess of sodium borohydride was neutralised by NH4Cl(aq) at 0°C, the resulting solution diluted by EtOAc and the organic layer treated by water and brine, After drying (MgSO4)
, ) was suspended in 5 mL of dry DCM and put in an ice bath. N,N-diisopropylethylamine (1.1 mL, 6.490 mmoles, 5 eq.) and methoxymethyl chloride (493 µL, 6.490 mmoles, 5 eq.) are then injected slowly under inert atmosphere. After 2h the solution was perfectly clear and showed no more starting material on TLC. The organic phase was treated by NH4Cl(aq), water and brine before being drying on MgSO4. After filtration, evaporation and purification on silica gel
, After 15 min, NH4Cl(aq) was introduced to quench the reaction and EtOAc was added to dilute the organic phase. The organic solution was treated by water and brine. After filtration, evaporation and purification on silica gel, Compound III-B-4 (357 mg, 1.247 mmoles, 1 eq.) was solubilised in 2.5 mL of dry THF, put in an ice bath and under argon
, Rf = 0.10 (50% EtOAc/Cx)
, Compound III-B-5 was added to a suspension of sodium hydride (60% in oil; 42 mg, 1.041 mmoles, 1.5 eq.) in 5 mL of dry THF under argon at 0°C. After 1h of stirring at this temperature, allyl bromide (90 µL, 1.041 mmoles, 1.5 eq.) was injected. The ice bath was removed and the mixture was stirred overnight at room temperature. The excess of sodium hydride was neutralised by NH4Cl(aq), the organic phase was diluted by DCM and washed several times with water and brine. After drying, filtration and concentration, the residue was purified on silica gel