Cyclization of Trichloroacetimidates
3
(E)-4-(2-Phenylvinyl)-2-(trichloromethyl)-4,5-dihydro-1,3-oxazole CH2], 4.38 (quintet, J = 5.7 Hz, 2 H, CH2O), 4.22 [q, J = 5.4 Hz,
[(E)-3j)]: Compound (E)-3j is a known compound.[8]
1 H, =CH-CH(N=)], 2.32 [octet, 3J = 6.6 Hz, 1 H, CH(CH3)2],
2.06 (m, 1 H, CH2-CH2O), 1.73 (m, 1 H, CH2CH2O-), 1.00 [d, J
3
(Z)-4-(2-Phenylvinyl)-2-(trichloromethyl)-4,5-dihydro-1,3-oxazole
[(Z)-3j)]: Obtained as a mixture with the E isomer. NMR spectra
were recorded of the mixture of E and Z isomers. Colourless oil.
= 6.6 Hz, 6 H, CH(CH3)2] ppm. 13C NMR (100 MHz, CDCl3): δ =
153.42, 139.64, 126.93, 64.98, 52.91, 30.80, 26.65, 22.29, 22.27 ppm.
GC–MS (EI): m/z (%) = 269 (1) [M]+, 253 (1), 234 (100), 226 (33),
198 (19), 166 (26), 156 (15), 124 (26), 117 (34), 108 (40), 93 (74),
81 (44), 67 (20), 53 (33). HRMS (EI): calcd. for C10H15Cl3NO [M
+ H]+ 270.0219; found 270.0155.
1H NMR (200 MHz, CDCl3): δ = 7.2–7.5 (m, 5 H, Ar), 6.74 (d, J
3
3
2
= 11.3 Hz, 1 H, Ph-CH=), 5.68 (dd, J = 11.0, J = 9.5 Hz, 1 H,
Ph-CH=CH), 5.05 [m, 1 H, =CH-CH(N=)CH2O], 4.84 (dd, 3J =
9.5, 2J = 8.1 Hz, 1 H, CH2O), 4.43 (t, 3J, 2J = 8.4 Hz, 1 H,
CH2O) ppm. GC–MS (EI): m/z (%) = 289 (3) [M]+, 255 (27), 224
(18), 182 (49), 154 (12), 142 (18), 128 (56), 115 (100), 104 (23), 91
(42), 77 (34), 63 (26), 51 (33), 39 (26).
(R)-N-(Trichloroacetyl)-[1-(hydroxymethyl)-4-methylpent-2-en-1-yl]-
amine (6): Water (1 mL) was added to the solution of oxazoline
(R)-(E)-3c (103.0 mg; 0.4 mmol) in EtOH (3 mL). The mixture was
heated at reflux for 18 h and then the solvent was removed under
reduced pressure and the residue purified by flash chromatography
on silica gel, eluting with a mixture of EtOAc and light petroleum
ether (1:3) to yield 50 mg (45%) of the amide 6 as a colourless
(E)-4-[2-(9-Anthryl)vinyl]-2-(trichloromethyl)-4,5-dihydro-1,3-ox-
azole [(E)-3k)]: Yellowish crystalline compound. M.p. 103–106 °C.
1H NMR (200 MHz, CDCl3): δ = 8.39 (s, 1 H, Ar), 8.25 (m, 2 H,
3
Ar), 7.99 (m, 2 H, Ar), 7.49 (m, 4 H, Ar), 7.43 (d, J = 16.0 Hz, 1
1
crystalline compound with m.p. 41–42 °C. H NMR (400 MHz,
H, Ar-CH=CH), 6.08 (dd, 3J = 16.0, 3J = 7.0 Hz, 1 H, Ar-
3
3
CDCl3): δ = 7.01 (br. s, 1 H, NH), 5.74 [ddd, J = 15.7, J = 6.3,
3
2
CH=CH), 5.34 [m, 1 H, =CH-, CH(N=)], 4.97 (dd, J = 9.4, J =
8.2 Hz, 1 H, CH2O-), 4.61 (t, 3J, 2J = 8.1 Hz, 1 H, CH2O) ppm.
13C NMR: δ = (100 MHz, CDCl3): 163.57, 135.33, 131.27, 131.18,
129.31, 129.07, 128.64, 126.76, 125.60, 125.57, 125.12, 86.54, 76.21,
68.72 ppm. HRMS (EI): calcd. for C20H15Cl3NO [M + H]+
390.0219; found 390.0405.
3
3
4J = 1.5 Hz, 1 H, (CH3)2CH-CH=], 5.41 [ddd, J = 15.7, J = 6.3,
4J = 1.5 Hz, 1 H, =CH-CH(N=)], 4.48 [m, 1 H, =CH-CH(N=)],
3
3.76 (m, 2 H, CH2OH), 2.33 [octet, J = 6.7 Hz, 1 H, CH(CH3)2],
1.84 (t, 3J = 5.5 Hz, 1 H, OH), 1.00 [d, 3J = 7.0 Hz, 6 H, CH(CH3)
2] ppm. 13C NMR (100 MHz, CDCl3): δ = 161.56, 141.97, 121.79,
92.66, 64.44, 54.52, 30.88, 22.14, 22.06 ppm. GC–MS (EI): m/z (%)
= 255 (1) [M – H2O]+, 242 (26), 231 (1), 208 (11), 173 (4), 117 (6),
95 (15), 81 (100), 69 (14), 55 (13). HRMS (EI): calcd. for
C9H14Cl3NNaO2 [M + Na]+ 295.9988; found 295.9961. [α]2D0 = –8.1
(c = 1.3, DCM).
(E)-4-(2-Methylprop-1-en-1-yl)-2-(trichloromethyl)-4,5-dihydro-1,3-
oxazole (3l): Colourless oil. 1H NMR (200 MHz, CDCl3): δ = 5.16
[d, 3J = 10.3 Hz, 1 H, (CH3)2C=CH], 5.05 [t, 3J = 8.8 Hz, 1 H,
=CH-CH(N=)], 4.75 (t, 3J, 2J = 8.8 Hz, 1 H, CH2O), 4.19 (t, J, 2J
3
= 8.8 Hz, 1 H, CH2O), 1.75 [s, 3 H, (CH3)2C=], 1.73 [s, 3 H, (CH3)2-
C=] ppm. 13C NMR (100 MHz, CDCl3): δ = 162.84, 137.56,
122.91, 76.67, 64.85, 51.87, 25.71, 18.45 ppm. GC–MS (EI): m/z
(%) = 241 (1) [M]+, 228 (4), 206 (18), 176 (22), 161 (24), 141 (14),
117 (12), 80 (100), 67 (32), 53 (31), 41 (60). Unstable in conditions
used for HRMS determination.
(R)-[1-(Hydroxymethyl)-4-methylpent-2-en-1-yl]amine Hydrochlo-
ride (7): Oxazoline (R)-3c (0.80 g; 3.1 mmol) was dissolved in a
mixture of EtOH (15 mL) and 6 aq. HCl (6 mL). The resulting
mixture was stirred at room temperature for 12 h and the solvents
evaporated. The residue was twice suspended in toluene (15 mL),
the solvent evaporated and then treated with EtOAc (7 mL). The
precipitate was collected on a filter and washed with additional
EtOAc (3 mL). The product was dried in reduced pressure over
P2O5 to give amino alcohol 7 (0.34 g, 65%) as a colourless very
hygroscopic crystalline compound with m.p. 95–97 °C. 1H NMR
(400 MHz, DMSO): δ = 8.12 (br. s, 3 H, NH3+), 5.77 [dd, 3J =
(E)-4-(2-Phenylprop-1-en-1-yl)-2-(trichloromethyl)-4,5-dihydro-1,3-
oxazole [(E)-3m)]: Colourless oil. 1H NMR (400 MHz, CDCl3): δ
3
= 7.2–7.5 (m, 5 H, Ar), 5.75 [d, J = 9.0 Hz, 1 H, Ph(Me)C=CH],
3
3
2
5.28 [q, J = 9.0 Hz, 1 H, =CH-CH(N=)], 4.87 (dd, J = 10.0, J
= 8.2 Hz, 1 H, CH2O), 4.33 (t, 3J, 2J = 8.2 Hz, 1 H, CH2O-), 2.15 (s,
3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 163.26, 142.31,
139.54, 128.31, 127.65, 125.93, 125.63, 77.204, 65.28, 16.75 ppm.
GC–MS (EI): m/z (%) = 303 (8) [M]+, 288 (5), 268 (32), 238 (14),
196 (14), 156 (16), 142 (100), 128 (49), 115 (52), 103 (22), 91 (20),
77 (18), 51 (11). Unstable in conditions used for HRMS determi-
nation.
3
3
3
15.8, J = 6.3 Hz, 1 H, (CH3)2CH-CH=], 5.35 [ddd, J = 15.8, J
= 7.0, 4J = 1.2 Hz, 1 H, =CH-CH(N=)], 3.56 [m, 1 H, =CH-
CH(N=)], 3.51 (dd, 2J = 11.2, 3J = 4.3 Hz, 1 H, CH2OH), 3.43 (dd,
3
2J = 11.2, J = 7.2 Hz, 1 H, CH2OH), 3.33 (br. s, 1 H, OH), 2.24
3
4
[octet of doublets, J = 6.6, J = 1.2 Hz, 1 H, CH(CH3)2], 0.92 [d,
3J = 6.6 Hz, 6 H, CH(CH3)2] ppm. 13C NMR (100 MHz, DMSO):
δ = 142.56, 120.90, 61.81, 54.17, 30.23, 21.73, 21.70 ppm.
C7H16ClNO·H2O (183.68): calcd. C 45.77, H 9.88, N 7.63; found
C 45.43, H 9.46, N 7.63. [α]2D0 = –15.5 (c = 1.5, MeOH).
(Z)-4-(2-Phenylprop-1-en-1-yl)-2-(trichloromethyl)-4,5-dihydro-1,3-
oxazole [(Z)-3m)]: Colourless oil. 1H NMR (400 MHz, CDCl3): δ =
4
7.2–7.5 (m, 5 H, Ph), 5.49 [dd, 3J = 9.0, J = 1.3 Hz, 1 H, Ph(Me)-
3
3
C=CH], 4.86 [q, J = 9.1 Hz, 1 H, =CH-CH(N=)], 4.62 (dd, J =
(S)-(Z)-1-Isopropyl-4-[(p-tolylsulfonylcarbamoyl)oxy]but-2-en-1-yl
Acetate (8): N-Tosylcarbamate 8 was synthesized in analogy to the
synthesis of the known racemic compound.[7f] Colourless amorph-
9.7, 2J = 8.6 Hz, 1 H, CH2O), 4.25 (t, J, 2J = 8.8 Hz, 1 H, CH2O-
3
), 2.10 (d, 4J = 1.3 Hz, 3 H, CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 162.81, 141.97, 140.51, 128.38, 127.74, 127.45, 124.84,
75.57, 65.77, 25.46 ppm. GC–MS (EI): m/z (%) = 303 (5) [M]+, 288
(5), 268 (34), 238 (14), 196 (16), 156 (17), 142 (100), 128 (56), 115
(54), 103 (22), 91 (20), 77 (21), 51 (13). HRMS (EI): calcd. for
C14H15Cl3NNaO2 [M + H2O + Na]+ 343.9982; found 343.9986.
For 2D NOESY, HSQC, HMBC results, see the Supporting Infor-
mation
1
ous solid. H NMR (400 MHz, CDCl3): δ = 7.92 (d, J = 8.1 Hz, 2
3
H, Ar), 7.58 (br. s, 1 H, NHTos), 7.33 (d, J = 8.1 Hz, 2 H, Ar),
3
3
3
5.63 (dt, J = 11.3, J = 6.4 Hz, 1 H, =CH-CH2-O), 5.49 (ddt, J
3
4
3
= 11.3, J = 9.3, J = 1.5 Hz, 1 H, CH=CH-CH2), 5.12 [dd, J =
9.3, J = 7.2 Hz, 1 H, CH(OAc)CH=], 4.79 (ddd, J = 13.3, J =
3
2
3
4
2
3
4
6.4, J = 1.6 Hz, 1 H, CH2O), 4.68 (ddd, J = 13.3, J = 6.5, J =
1.6 Hz, 1 H, CH2-O), 2.44 (s, 3 H, CH3-C4H6), 2.04 [s, 3 H, C(=O)-
CH3], 1.80 [octet, J = 7.0 Hz, 1 H, (CH3)2CH], 0.88 [d, 3J = 7.0 Hz,
(E)-4-(3-Methylbut-1-en-1-yl)-2-(trichloromethyl)-5,6-dihydro-4H-
1,3-oxazine (5): Colourless oil. 1H NMR (400 MHz, CDCl3): δ =
3 H, (CH3)2CH], 0.82 [d, J = 7.0 Hz, 3 H, (CH3)2CH] ppm. 13C
3
3
3
4
5.58 [ddd, J = 15.5, J = 6.3, J = 1.2 Hz, 1 H, (CH3)2CH-CH=], NMR (100 MHz, CDCl3): δ = 170.39, 150.08, 145.04, 135.40,
5.46 [ddd, 3J = 15.5, 3J = 5.5, 4J = 0.8 Hz, 1 H, =CH-CH(N=)- 131.37, 129.56, 128.39, 126.70, 62.63, 31.93, 21.66, 21.06, 18.04,
Eur. J. Org. Chem. 2009, 6407–6412
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6411