Reactivity of Dehydroamino Acids and Dehydrodipeptides
164.24 (C=O), 156.53 (C=O), 125.66 (C), 122.82 (C), 80.73 (s, 3 H, CH3 Tos), 1.58 (d, J = 6.6 Hz, 3 H, CH3), 1.34 (d, J =
[C(CH3)3], 52.49 (OCH3), 44.33 (CH2), 28.21 (CH3 Boc), 25.61 6.6 Hz, 3 H, CH3) ppm. 13C NMR (CDCl3): δ = 173.06 (C=O),
(γCH3) ppm. C12H19BrN2O5 (351.19): calcd. C 41.04, H 5.45, N 172.69 (C=O), 168.07 (C=O), 167.57 (C=O), 144.73 (C), 144.57
7.98; found C 41.52, H 5.37, N 7.98. (Z)-13h: M.p. 83.0–85.0 °C (C), 136.68 (C), 136.36 (C), 129.73 (CH), 129.66 (CH), 127.88
(from diethyl ether/n-hexane). 1H NMR (CDCl3): δ = 7.92 (br. s, 1
H, NH ∆Abu), 5.27 (s, 1 H, NH Gly), 3.88 (d, J = 6.0 Hz, 2 H,
CH2), 3.80 (s, 3 H, CH3 CO2Me), 2.57 (s, 3 H, γCH3), 1.46 (s, 9
H, CH3 Boc) ppm. 13C NMR (CDCl3): δ = 167.94 (C=O), 162.84
(C=O), 156.18 (C=O), 126.51 (C), 124.88 (C), 80.66 [C(CH3)3],
52.63 (OCH3), 44.37 (CH2), 28.24 [C(CH3)3], 24.70 (γCH3) ppm.
C12H19BrN2O5 (351.19): calcd. C 41.04, H 5.45, N 7.98; found C
40.93, H 5.40, N 8.05.
(CH), 127.61 (CH), 78.70 (C), 78.06 (C), 57.12 (CH), 56.52 (CH),
53.92 (OCH3), 53.64 (OCH3), 37.19 (CH2), 35.92 (CH2), 21.58
(CH3 Tos), 18.54 (CH3), 17.09 (CH3) ppm. C14H17BrN2O5S
(405.26): calcd. C 41.49, H 4.23, N 6.91, S 7.91; found C 41.95, H
4.37, N 6.99, S 7.76.
Methyl 2-(1-Bromoethyl)-4-oxo-1-(4-tolylsulfonyl)imidazolidine-2-
carboxylate (14c): The procedure described above was used substi-
tuting compound 9c for 9a to give 14c as a white solid (0.19 g,
94%). M.p. 161.0–162.0 °C (from ethyl acetate/n-hexane). 1H NMR
(CDCl3): δ = 7.66 (d, J = 8.4 Hz, 2 H, ArH), 7.37 (d, J = 8.4 Hz,
2 H, ArH), 6.41 (s, 1 H, NH), 5.32 (q, J = 7.5 Hz, 1 H, CH), 4.15
(d, J = 14.4 Hz, 1 H, CH2), 3.91 (d, J = 14.4 Hz, 1 H, CH2), 3.44
(s, 3 H, CH3 CO2Me), 2.46 (s, 3 H, CH3 Tos), 1.86 (d, J = 7.5 Hz,
3 H, CH3) ppm. 13C NMR (CDCl3): δ = 168.11 (C=O), 166.17
(C=O), 145.04 (C), 133.97 (C), 129.78 (CH), 127.69 (CH), 81.37
(C), 53.08 (OCH3), 50.73 (CH2), 48.80 (CH), 21.58 (CH3 Tos),
18.74 (CH3) ppm. MS (FAB): m/z (%) = 407.02 (40.70), 405.02
(40.99) [M + 1]+, 346.99 (19.76), 344.99 (19.31) [M – CO2Me]+.
HRMS (FAB): calcd. for C14H17BrN2O5S 404.0042 [M + 1]; found
405.0105. C14H17BrN2O5S (405.26): calcd. C 41.49, H 4.23, N 6.91,
S 7.91; found C 41.64, H 4.39, N 6.91, S 8.00.
Boc-Gly-∆Phe(β-Br)-OMe (13j): The same procedure described for
the preparation of 5f was followed substituting 9j (1 mmol, 0.344 g)
for 3f to give 13j as a 1:1 E/Z mixture (0.359 g, 87%) that could
not be separated by column chromatography. 1H NMR (CDCl3): δ
= 8.28 (s, 1 H, NH ∆Phe), 7.90 (s, 1 H, NH ∆Phe), 7.41 (br. s, 5
H, ArH), 7.36 (br. s, 5 H, ArH), 5.36 (br. t, J = 5.7 Hz, 1 H, NH
Gly), 5.16 (br. s, 1 H, NH Gly), 3.93 (d, J = 5.7 Hz, 2 H, CH2),
3.90 (s, 3 H, CH3 CO2Me), 3.72 (d, J = 6.0 Hz, 2 H, CH2), 3.51 (s,
3 H, CH3 CO2Me), 1.48 (s, 9 H, CH3 Boc), 1.34 (s, 9 H, CH3
Boc) ppm. 13C NMR (CDCl3): δ = 167.98 (C=O), 167.27 (C=O),
164.42 (C=O), 163.33 (C=O), 156.26 (C=O), 155.98 (C=O), 137.00
(C), 136.15 (C), 129.68 (CH), 129.40 (CH), 128.98 (CH), 128.83
(CH), 128.51 (C), 128.33 (C), 128.24 (CH), 127.53 (C), 125.88 (C),
80.85 [C(CH3)3], 80.61 [C(CH3)3], 52.72 (OCH3), 52.56 (OCH3),
44.53 (CH2), 44.13 (CH2), 28.27 [C(CH3)3], 28.14 [C(CH3)3] ppm.
C17H21BrN2O5 (413.26): calcd. C 49.41, H 5.12, N 6.78; found C
49.35, H 5.19, N 7.00.
Methyl
2-(1-Bromoethyl)-5-methyl-4-oxo-1-(4-tolylsulfonyl)imid-
azolidine-2-carboxylate (14d): The procedure described above was
used substituting compound 9d for 9a to give 14d as a dia-
stereomeric mixture (0.16 g, 74%). The diastereomers were isolated
by column chromatography through silica using diethyl ether/petro-
leum ether as eluent. Diastereomer 1: m.p. 180.0–181.0 °C. 1H
NMR (CDCl3): δ = 7.72 (d, J = 8.1 Hz, 2 H, ArH), 7.33 (d, J =
8.1 Hz, 2 H, ArH), 6.59 (br. s, 1 H, NH), 5.51 (q, J = 6.6 Hz, 1 H,
CH), 4.37 (q, J = 6.9 Hz, 1 H, CH), 3.57 (s, 3 H, CH3 CO2Me),
2.45 (s, 3 H, CH3 Tos), 1.84 (d, J = 6.6 Hz, 3 H, CH3), 1.42 (d, J
= 6.9 Hz, 3 H, CH3) ppm. 13C NMR (CDCl3): δ = 170.95 (C=O),
167.40 (C=O), 144.62 (C), 137.47 (C), 129.24 (CH), 127.62 (CH),
81.17 (C), 58.59 (CH), 53.25 (OCH3), 50.63 (CH), 21.56 (CH3 Tos),
18.74 (CH3), 17.94 (CH3) ppm. C15H19BrN2O5S (419.29): calcd. C
42.97, H 4.57, N 6.68, S 7.65; found C 43.01, H 4.62, N 6.66, S
Synthesis of 1-(4-Tolylsulfonyl)imidazolidin-4-one Derivatives 14a–
f,k
Methyl 2-(Bromomethyl)-4-oxo-1-(4-tolylsulfonyl)imidazolidine-2-
carboxylate (14a): N-Bromosuccinimide (1.1 equiv., 0.55 mmol)
was added to a solution of Tos-Gly-∆Ala-OMe (9a) (0.5 mmol) in
dichloromethane (0.1 moldm–3). The reaction was stirred at room
temperature for 18 h and then triethylamine (1.1 equiv.) was added.
After 4 h at room temperature, dichloromethane (25 mL) was
added and the organic phase washed with water and brine
(3ϫ10 mL). After drying with MgSO4 the extract was taken to
dryness at reduced pressure to afford compound 14a as a white
solid (0.18 g, 92%). M.p. 150.0–151.0 °C (from ethyl acetate/n-hex-
1
7.47. Diastereomer 2: H NMR (CDCl3): δ = 7.62 (d, J = 8.1 Hz,
1
2 H, ArH), 7.36 (d, J = 8.1 Hz, 2 H, ArH), 6.54 (br. s, 1 H, NH),
5.22 (q, J = 6.6 Hz, 1 H, CH), 4.06 (q, J = 6.9 Hz, 1 H, CH), 3.39
(s, 3 H, CH3 CO2Me), 2.46 (s, 3 H, CH3 Tos), 1.82 (d, J = 6.6 Hz,
3 H, CH3), 1.69 (d, J = 6.9 Hz, 3 H, CH3) ppm. 13C NMR (CDCl3):
δ = 171.43 (C=O), 166.36 (C=O), 145.02 (C), 133.87 (C), 129.74
(CH), 127.91 (CH), 80.63 (C), 58.00 (CH), 48.91 (OCH3), 52.98
(CH), 21.60 (CH3 Tos), 19.36 (CH3), 19.21 (CH3) ppm.
C15H19BrN2O5S (419.29): calcd. C 42.97, H 4.57, N 6.68, S 7.65;
found C 42.61, H 4.59, N 6.60, S 7.30.
ane). H NMR (CDCl3): δ = 7.75 (d, J = 8.1 Hz, 1 H, ArH), 7.35
(d, J = 8.1 Hz, 1 H, ArH), 7.27 (br. s, 1 H, NH), 4.23 (d, J =
12.0 Hz, 1 H, CH2), 4.13 (d, J = 12.0 Hz, 1 H, CH2), 4.06 (d, J =
14.1 Hz, 1 H, CH2), 3.89 (d, J = 14.1 Hz, 1 H, CH2), 3.77 (s, 3 H,
CH3 CO2Me), 2.46 (s, 3 H, CH3 Tos) ppm. 13C NMR (CDCl3): δ =
169.64 (C=O), 167.28 (C=O), 144.77 (C), 135.07 (C), 129.76 (CH),
127.50 (CH), 78.98 (C), 53.72 (OCH3), 36.49 (CH2), 21.57 (CH3
Tos) ppm. MS (FAB): m/z (%) = 392.97 (26.21) and 390.97 (27.24)
[M + 1]+, 332.94 (12.46), 330.95 (12.41) [M – CO2Me]+. HRMS
(FAB): calcd. for C13H15BrN2O5S 389.9885 [M + 1]; found
390.9952. C13H15BrN2O5S (391.24): calcd. C 39.91, H 3.86, N 7.16,
S 8.20; found C 39.66, H 4.00, N 7.03, S 8.00.
Methyl 2-[Bromo(phenyl)methyl]-4-oxo-1-(4-tolylsulfonyl)imidazol-
idine-2-carboxylate (14e): The procedure described above was used
substituting compound 9e for 9a to give 14e as a diastereomeric
mixture (0.20 g, 86%). 1H NMR (CDCl3): δ = 7.80–7.29 (m, 20 H,
ArH + NH), 7.08 (s, 1 H, NH), 6.37 (s, 1 H, CH), 6.19 (s, 1 H,
CH), 4.20 (d, J = 14.1 Hz, 1 H, CH2), 3.98 (d, J = 14.1 Hz, 1 H,
CH2), 3.69 (d, J = 14.7 Hz, 1 H, CH2), 3.60 (s, 3 H, CH3 CO2Me),
3.42 (s, 3 H, CH3 CO2Me), 3.12 (d, J = 14.7 Hz, 1 H, CH2), 2.45
(s, 3 H, CH3 Tos), 2.42 (s, 3 H, CH3 Tos) ppm. 13C NMR (CDCl3):
δ = 169.02 (C=O), 168.56 (C=O), 166.11 (C=O), 165.14 (C=O),
144.80 (C), 144.67 (C), 135.73 (C), 134.99 (C), 134.83 (C), 134.46
Methyl
2-(Bromomethyl)-5-methyl-4-oxo-1-(4-tolylsulfonyl)imid-
azolidine-2-carboxylate (14b): The procedure described above was
used substituting compound 9b for 9a to give 14b (0.357 mg, 88%)
as a diastereomeric mixture. 1H NMR (CDCl3): δ = 7.78 (d, J =
8.1 Hz, 2 H, ArH), 7.67 (s, 1 H, NH), 7.34 (d, J = 8.1 Hz, 2 H,
ArH), 4.36 (q, J = 6.6 Hz, 1H, CH), 4.33 (d, J = 12.0 Hz, 1 H,
CH2), 4.19 (d, J = 12.3 Hz, 1 H, CH2), 4.15 (d, J = 12.0 Hz, 1 H,
CH2), 4.12 (d, J = 12.3 Hz, 1 H, CH2), 4.07 (q, J = 6.6 Hz, 1 H,
CH), 3.82 (s, 3 H, CH3 CO2Me), 3.80 (s, 3 H, CH3 CO2Me), 2.45 (C), 130.98 (CH), 130.04 (CH), 129.67 (CH), 129.42 (CH), 128.62
Eur. J. Org. Chem. 2007, 5934–5949
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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