848
C. M. Zammit, M. Wills / Tetrahedron: Asymmetry 24 (2013) 844–852
(C), 138.27 (C), 137.08 (C), 129.10 (2 ꢂ CH), 128.32 (2 ꢂ CH),
127.89 (2 ꢂ CH), 127.63 (2 ꢂ CH), 127.50 (CH), 127.45 (2 ꢂ CH),
127.26 (CH), 127.17 (2 ꢂ CH), 79.64 („CH), 74.62 (C„CH), 69.18
(CH2), 67.78 (CH), 63.13 (CH), 58.17 (CH2), 46.46 (CH2), 21.45
(CH3); ESI-MS m/z (CI) 449 (M++H), 471 (M++Na).
ourless oil; ½a 3D0
ꢃ
¼ þ4:7 (c 0.315, CHCl3); (found (EI): M++H,
580.2758. C34H38N5O2S requires M 580.2741);
m
max/cmꢀ1 (thin
film) 3254 (NH), 2926 and 2858 (CH2), 1600, 1454, 1320 and
1153 (SO2), 811 (p-substituted Ph), 760 and 698 (Ph), 666; dH
(700 MHz, CDCl3) 7.38–7.33 (5H, m, ArH), 7.28–7.26 (2H, m,
ArH), 7.21 (1H, s, CH of triazole), 7.11–7.10 (3H, m, ArH), 7.04–
6.98 (5H, m, ArH), 6.91–6.87 (4H, m, ArH), 6.35 (1H, br s, NH),
5.50 (2H, s, CH2Ph), 4.23 (1H, d, J 9.1, PhCHNHTs), 3.59 (1H, d, J
9.1, PhCHNHCH2), 2.64 (2H, t, J 8.8, CH2C(C)N), 2.43–2.39 (1H, m,
NHCHaHbCH2), 2.32 (3H, s, CH3 of NHTs), 2.32–2.27 (1H, m,
NHCHaHbCH2), 1.66–1.55 (2H, m, NHCH2CH2CH2), 1.48–1.37 (2H,
m, NHCH2CH2CH2); dC (176 MHz, CDCl3) 148.33 (C), 142.65 (C),
139.17 (C), 138.18 (C), 136.97 (C), 134.95 (C), 129.02 (4 ꢂ CH),
128.56 (CH), 128.23 (2 ꢂ CH), 127.98 (2 ꢂ CH), 127.80 (2 ꢂ CH),
127.54 (2 ꢂ CH), 127.40 (CH), 127.36 (2 ꢂ CH), 127.16 (CH),
127.06 (2 ꢂ CH), 120.65 (CH of triazole), 67.69 (CH), 63.04 (CH),
53.96 (CH2), 46.64 (CH2), 29.30 (CH2), 26.78 (CH2), 25.36 (CH2),
21.38 (CH3). ESI-MS m/z (CI) 580 (M++H), 602 (M++Na).
4.7. Synthesis of N-[(R,R)-2-(hex-5-ynylamino)-1,2-diphenyl-
ethyl]-4-methyl benzenesulfonamide 10
To a stirred solution of hexyn-1-ol (1.04 g, 10.6 mmol) and 2,6-
lutidine (2.38 g, 22.2 mmol) in dichloromethane (21 cm3) was
added dropwise trifluoromethanesulfonic anhydride (4.78 g,
16.95 mmol) at 0–5 °C. The solution was then stirred at 5–10 °C
for 1 h, heated to 22 °C and stirred at this temperature for 1.5 h.
In
a separate round-bottomed flask, triethylamine (1.61 g,
15.9 mmol) was added to a solution of (R,R)-TsDPEN (2.32 g,
6.33 mmol) in dichloromethane (10 cm3) at 5 °C. The triflate solu-
tion was then added dropwise to this TsDPEN solution whilst
maintaining the temperature between 0–5 °C. The reaction mix-
ture was warmed to rt and left to stir overnight. The solution
was then diluted with saturated NaHCO3 (50 cm3) and extracted
with dichloromethane (24 cm3). The organic layer was washed fur-
ther with saturated NaHCO3 (3 ꢂ 20 cm3), water (2 ꢂ 50 cm3), sat-
urated NaCl (50 cm3), dried (Na2SO4) and concentrated under
reduced pressure. The residue was purified by flash column chro-
matography (16/84 v/v EtOAc/petroleum ether) to give 10
(1.11 g, 2.49 mmol, 39.3%) as a white solid; Mp 95–97 °C; (found
4.9. Synthesis of N-[(R,R)-2-(1-phenoxymethyl-1H-1,2,3-triazol-
4-yl)methoxy ethylamino)-1,2-diphenylethyl]-4-methylbenzene-
sulfonamide 8
To a stirred solution of [(2-azidoethoxy)methyl]benzene 7
(0.030 g, 0.17 mmol) in tert-butanol:water (8:2 v/v, 1.3 cm3) was
added
N-[(R,R)-2-(prop-2-ynyloxyethylamino)-1,2-diphenyl-
ethyl]-4-methylbenzene sulfonamide 6 (0.076 g, 0.17 mmol). So-
dium ascorbate (3.3 ꢂ 10ꢀ3 g, 0.017 mmol) and copper(II) sulfate
pentahydrate (0.021 g, 0.08 mmol) were added sequentially and
the reaction mixture was stirred at 30 °C for 5 h whilst monitoring
by TLC (Rf product = 0.48, Rf starting alkyne = 0.85; eluent:
EtOAc = 100%; potassium permanganate stain). The pale blue solu-
tion was concentrated under reduced pressure and the oily residue
was dissolved in a mixture of water (2.5 cm3) and ethyl acetate
(3 cm3). The water layer was re-extracted with EtOAc (3 cm3)
and the organic layers combined, washed with 6% (w/v) NaCl solu-
tion, dried (Na2SO4) and concentrated under reduced pressure. The
residue was purified by flash column chromatography using gradi-
ent elution from 70/30 to 75/25 v/v EtOAc/petroleum ether to give
(EI): M++H, 447.2105. C27H31N2O2S requires
¼ ꢀ26:6 (c 0.38, CHCl3);
max/cmꢀ1 (solid) 3281 („CH),
M 447.2101);
½
a 2D4
ꢃ
m
2932 and 2859 (CH2), 2324 (C„C), 1601, 1326 and 1159 (SO2),
1086 (C–O–C), 816 (Ph), 762 and 699 (Ph), 669; dH (400 MHz,
CDCl3) 7.38 (2H, d, J 8.4, ArH), 7.14–6.89 (12H, m, ArH), 6.25 (1H,
br s, NHTs), 4.25 (1H, d, J 8.0, PhCHNHTs), 3.61 (2H, d, J 8.0,
PhCHNHCH2), 2.44–2.37 (1H, m, NHCHaHbCH2), 2.33 (3H, s, CH3
of NTs), 2.33–2.26 (1H, m, NHCHaHbCH2), 2.15–2.12 (2H, m,
CH2C„CH), 1.93 (1H, t,
J 2.6, „CH), 1.56–1.41 (4H, m,
NHCH2CH2CH2), 1.23 (1H, br s, NH); dC (100 MHz, CDCl3) 142.63
(C), 139.19 (C), 138.25 (C), 136.97 (C), 129.01 (2 ꢂ CH), 128.21
(2 ꢂ CH), 127.81 (2 ꢂ CH), 127.48 (2 ꢂ CH), 127.37 (CH), 127.32
(2 ꢂ CH), 127.16 (CH), 127.04 (2 ꢂ CH), 84.12 („CH), 68.47
(C„CH), 67.74 (CH), 63.01 (CH), 46.49 (CH2), 28.95 (CH2), 25.87
(CH2), 21.35 (CH3), 18.14 (CH2). ESI-MS m/z (CI) 447 (M++H), 469
(M++Na).
8 (0.064 g, 0.10 mmol, 60.5%) as a colourless oil; ½a D32
¼ þ6:7 (c
ꢃ
0.115, CHCl3); (found (EI): M++H, 626.2801. C35H40N5O4S requires
M, 626.2796); m
max/cmꢀ1 (thin film) 3272 (NH), 2919 and 2866
(CH2), 1720, 1600, 1453, 1319 and 1154 (SO2), 1093, 932, 813 (p-
substituted Ph), 768 and 699 (Ph), 667; dH (400 MHz, CDCl3) 7.71
(1H, s, CH of triazole), 7.37–7.25 (7H, m, ArH), 7.10–7.09 (3H, m,
ArH), 7.01–6.95 (5H, m, ArH), 6.92–6.86 (4H, m, ArH), 4.59 (over-
lapping 2H, s, CH2C(C)N and 2H, t, J 5.2, PhCH2OCH2), 4.52 (2H, s,
PhCH2OCH2), 4.25 (1H, d, J 8.2, PhCHNHTs), 3.87 (2H, t, J 5.2,
PhCH2OCH2CH2), 3.67 (1H, d, J 8.2, PhCHNHCH2), 3.61–3.56 (1H,
qd, NHCH2CHaHbO), 3.51–3.47 (1H, m, NHCH2CHaHbO), 2.68–2.63
(1H, m, NHCHaHbCH2O), 2.52–2.46 (1H, m, NHCHaHbCH2O), 2.31
(3H, s, CH3 of NHTs); dC (100 MHz, CDCl3) 144.88 (C), 142.58 (C),
139.18 (C), 138.21 (C), 137.12 (C), 129.01 (2 ꢂ CH), 128.49
(2 ꢂ CH), 128.21 (2 ꢂ CH), 127.91 (CH), 127.78 (2 ꢂ CH), 127.68
(2 ꢂ CH), 127.54 (overlapping CH and 2 ꢂ CH), 127.53 (2 ꢂ CH),
127.40 (CH), 127.08 (2 ꢂ CH), 123.71 (CH of triazole), 73.25
(CH2), 69.29 (CH2), 68.28 (CH2), 67.55 (CH), 64.32 (CH2), 63.28
(CH), 50.33 (CH2), 46.44 (CH2), 21.38 (CH3); ESI-MS m/z (CI) 626
(M++H), 648 (M++Na).
4.8. Synthesis of N-[(R,R)-2-(1-benzyl-1H-1,2,3-triazol-4-yl)butyl-
amino)-1,2-diphenylethyl]-4-methylbenzene-sulfonamide 9
To a stirred solution of benzyl bromide (0.083 g, 0.48 mmol) in
tert-butanol:water (1:1 v/v, 1.2 cm3) were added N-[(R,R)-2-(hex-
5-ynylamino)-1,2-diphenylethyl]-4-methylbenzene-sulfonamide
10 (0.22 g, 0.49 mmol) and sodium azide (0.033 g, 0.51 mmol). So-
dium ascorbate (9.6 ꢂ 10ꢀ3 g, 0.048 mmol) and copper(II) sulfate
pentahydrate (6.0 ꢂ 10ꢀ3 g, 0.024 mmol) were then added sequen-
tially to this solution the reaction mixture was stirred at 60 °C for
3 h (whilst monitoring by TLC and mass spectrometry). The resul-
tant brown solution was quenched with cold water (1.8 cm3) and
10% aqueous ammonia solution (0.4 cm3); the mixture was then
stirred for 15 min. The mixture was concentrated under reduced
pressure to remove tert-butanol and the residue was dissolved in
a solution of water (5 cm3) and EtOAc (6 cm3). The water layer
was re-extracted with ethyl acetate (5 cm3) and the organic layers
combined, washed with water (10 cm3), dried (MgSO4) and con-
centrated under reduced pressure. The residue was purified by
flash column chromatography using gradient elution from 70/30
to 80/20 v/v EtOAc/petroleum ether (silica column pre-treated
with 1% triethylamine) to give 9 (0.19 g, 0.33 mmol, 66.6%) as a col-
4.10. Synthesis of HEMA/MMA copolymers 12a–c
The synthesis of polymer 12b is provided as a representative
procedure for the polymerisation of HEMA and MMA with 4,40-azo-
bis(4-cyanovaleric acid) as the initiator and CoBF as the catalyst.
MMA and HEMA were purified by being passed through basic alu-