Cycloadditions of Halogen-Substituted 2(H)-Pyran-2-ones
CH3), 169.1 (C-3), 138.78 (C-8), 130.0 (C-7), 73.8 (C-1), 64.8
(C-4), 53.2 (CO2CH3), 44.8 (C-6), 34.6 (C-5); IR 3081, 2952,
2922, 2852, 1780, 1738, 1436, 1364, 1306, 1259, 1205, 1116,
1057, 1025, 969, 927, 799, 714 cm-1; m/z 219 (7), 218 (6), 217
(10, MH+), 185 [10, (M+ - OMe)], 172 [25, (M+ - CO2)], 157
[6, (M+ - CO2Me)], 137 [15, (M+ - CO2 - Cl)], 115 (32), 114
(20), 113 [100, (M+ - CO2,CO2Me)], 112 (43), 102 (9), 78 (12),
77 (73), 65 (7), 55 (12), 51 (11); HRMS (ESI) calcd for C9H9-
35ClO4Na 239.00816, found 239.00752.
229 [11, (M+ for 79Br-OMe)], 218 [16, (M+ for 81Br-CO2)], 217
(24), 216 [16, (M+ for 79Br-CO2)], 215 (21), 203 (10), 201 (12),
187 (9), 185 (11), 176 [8, (M+ for 81Br - 86, retro-Diels-Alder)],
174 [9, (M+ for 79Br - 86, retro-Diels-Alder)], 160 (11), 159
[99, (M+ for 81Br-CO2-CO2Me)], 158 (50), 157 [100, (M+ for
79Br-CO2-CO2Me)], 156 (45), 147 (11), 145 (11), 137 (45), 93
(32), 78 (44), 77 (64), 65 (5), 60 (8), 59 (11), 55 (11); HRMS
calcd for C9H979BrO4Na 282.95764, found 282.95723.
Typical Cycloaddition: Reaction of 5-Iodo-2(H)-
pyran-2-one and (2-Chloroethyl) Vinyl Ether. A sealed
pressure tube (purchased from Aldrich Chemical Co. Cat. No.
Z18,109-9) was charged with 5-iodo-2(H)-pyran-2-one (13) (48
mg, 0.216 mmol), (2-chloroethyl) vinyl ether (0.5 mL, 6.1 mmol,
28 equiv), a few crystals of 2,6-di-tert-butyl-4-methylphenol
(acting as an antipolymerization agent), and a small magnetic
stirrer bar. The pressure tube was sealed and then immersed
in an oil bath maintained at 100 °C. After 3 days, the tube
was cooled to room temperature and the contents were
stripped of volatile materials. Proton nuclear magnetic reso-
nance of the crude residue indicated the presence of two
cycloadducts. A pure sample of the mixed isomers was obtained
by silica gel chromatography, using 20% v/v ethyl acetate in
petroleum ether. The combined isolated yield of cycloadducts
was 65 mg, 92%.
Typical Cycloaddition: Reaction of 5-Bromo-2(H)-
pyran-2-one and Methyl Acrylate. A sealed pressure tube
(purchased from Aldrich Chemical Co. Cat. No. Z18, 109-9)
was charged with 5-bromo-2(H)-pyran-2-one (5) (66 mg, 0.38
mmol), methyl acrylate (0.6 mL, 6.7 mmol, 18 equiv), a few
crystals of 2,6-di-tert-butyl-4-methylphenol (acting as an an-
tipolymerization agent) and a small magnetic stirrer bar. The
pressure tube was sealed and immersed in an oil bath
maintained at 100 °C. After 3 days, the tube was cooled to
room temperature and the contents were stripped of volatile
materials. Proton nuclear magnetic resonance of the crude
residue indicated the presence of 3 isomers of cycloadducts.
Silica gel chromatography with 30% v/v ethyl acetate in
petroleum ether afforded pure samples of the 5-endo and 5-exo
cycloadducts as well as a sample of the 6-endo product
contaminated with traces of the 5-endo and 5-exo cycloadducts.
The combined isolated yield of cycloadducts was 93 mg, 94%.
Methyl 7-bromo-3-oxo-2-oxabicyclo[2.2.2]oct-7-ene-
7-Iodo-5endo-(2-chloroethoxy)-3-oxo-2-oxabicyclo[2.2.2]-
oct-7-ene and 7-iodo-5exo-(2-chloroethoxy)-3-oxo-2-oxa-
1
bicyclo[2.2.2]oct-7-ene: H NMR 5-endo cycloadduct δ 6.76
5
endo-carboxylate: 1H NMR δ 6.53 (dd, 1H, J1,8 ) 2.4 Hz,
(dd, 1H, J1,8 ) 1.7 Hz, J4,8 ) 6.5 Hz, H-8), 5.17 (dt, 1H, J1,6endo
J4,8 ) 6.5 Hz, H-8), 5.16 (m, 1H, H-1), 3.91 (dd, 1H, J4,5 ) 2.7
Hz, J4,8 ) 6.5 Hz, H-4), 3.72 (s, 3H, CO2CH3), 3.05 (dm, 1H,
≈ J1,8 ) 1.7 Hz, J1,6exo ) 3.8 Hz, H-1), 4.01 (dm, 1H, J5,6exo
)
7.8 Hz, H-5), 3.84 (dd, 1H, J4,5 ) 3.2 Hz, J4,8 ) 6.5 Hz, H-4),
3.69 (m, 2H, OCH2CH2Cl), 3.57 (dd, 2H, J ) 5.6 Hz, 11.1 Hz,
OCH2CH2Cl), 2.51 (ddd, 1H, J1,6exo ) 3.8 Hz, J5,6exo ) 7.8 Hz,
J6exo,6endo ) 14.3 Hz, H-6exo), 1.76 (dm, 1H, J6exo,6endo ) 14.3 Hz,
H-6endo), and 5-exo cycloadduct δ 6.76 (dd, 1H, J1,8 ) 1.9 Hz,
J4,8 ) 6.7 Hz, H-8), 5.14 (m, 1H, H-1), 3.89 (dt, 1H, J4,5 ≈ J5,6exo
J5,6exo ) 9.4 Hz, H-5), 2.50 (ddd, 1H, J1,6exo ) 3.9 Hz, J5,6exo
9.8 Hz, J6exo,6endo ) 14.0 Hz, H-6exo), 2.26 (ddd, 1H, J1,6endo
)
)
1.4 Hz, J5,6endo ) 4.0 Hz, J6exo,6endo ) 14.0 Hz, H-6endo); 13C NMR
δ 171.7 (C-3), 170.8 (CO2CH3), 129.3 (C-8), 122.0 (C-7), 80.9
(C-1), 53.2 (CO2CH3), 45.5 (C-4), 37.2 (C-5), 30.1 (C-6); IR 3005,
2954, 2850, 1766, 1734, 1615, 1436, 1359, 1275, 1235, 1214,
1158, 1073, 1042, 1014, 995, 951, 902, 808, 783, 767, 736, 642,
521 cm-1; m/z 262 (14, M+ for 81Br), 260 (14, M+ for 79Br), 231
[17, (M+ for 81Br-OMe), 229 [18, (M+ for 79Br-OMe)], 218 [16,
(M+ for 81Br-CO2)], 216 [16, (M+ for 79Br-CO2)], 187 (6), 185
(6), 176 [14, (M+ for 81Br - 86, retro-Diels-Alder)], 174 [14,
(M+ for 79Br - 86, retro-Diels-Alder)], 159 [90, (M+ for 81Br-
CO2-CO2Me)], 158 (40), 157 [93, (M+ for 79Br-CO2-CO2Me)],
156 (34), 147 (11), 145 (11), 93 (37), 78 (95), 77 (100), 65 (11),
60 (10), 59 (19), 55 (60); HRMS calcd for C9H979BrO4Na
282.95825, found 282.95796. Anal. Calcd for C9H9BrO4: C,
41.41, H, 3.47. Found: C, 41.61, H, 3.34.
) 3.3 Hz, 3.3 Hz, J5,6endo ) 8.8 Hz, H-5), 3.75 (dd, 1H, J4,5
3.3 Hz, J4,8 ) 6.7 Hz, H-4), 3.68-3.60 (m, 4H, OCH2CH2Cl),
2.30 (ddd, 1H, J1,6endo ) 1.5 Hz, J5,6endo ) 8.8 Hz, J6exo,6endo
)
)
14.1 Hz, H-6endo), 1.96 (dt, 1H, J1,6exo ≈ J5,6exo ) 3.4 Hz, J6exo,6endo
) 14.1 Hz, H-6exo); 13C NMR 5-endo cycloadduct δ 170.1 (C-3),
136.5 (C-8), 90.6 (C-7), 83.7 (C-1), 71.9 (C-5), 69.8 (OCH2CH2-
Cl), 50.1 (C-4), 43.0 (OCH2CH2Cl), 34.9 (C-6), and 5-exo
cycloadduct δ 170.1 (C-3), 136.4 (C-8), 94.4 (C-7), 83.8 (C-1),
73.5 (C-5), 69.8 (OCH2CH2Cl), 49.9 (C-4), 42.8 (OCH2CH2Cl),
33.7 (C-6); IR 3076, 2956, 2924, 2863, 1761, 1684, 1601, 1460,
1430, 1355, 1301, 1260, 1169, 1113, 1025, 1008, 990, 917, 874,
800, 762, 738, 666, 638, 623 cm-1; m/z 330 (10), 328 (27, M+),
223 (13), 222 [100, (M+ - 106, retro Diels-Alder)], 194 (33),
109(12), 108 (36), 107 (31), 106 [87, (M+ - 222, retro-Diels-
Alder)], 95 (10), 78 (17), 77 (8), 66 (7), 65 (11), 63 (29), 62 (6),
57 (6); HRMS calcd for C9H1035ClIO3Na 350.925536, found
350.92643.
Methyl 7-bromo-3-oxo-2-oxabicyclo[2.2.2]oct-7-ene-
6
endo-carboxylate: 1H NMR δ 6.68 (dd, 1H, J1,8 ) 2.6 Hz,
J4,8 ) 6.8 Hz, H-8), 5.42 (dd, 1H, J1,8 ) 2.6 Hz, J1,6 ) 3.9 Hz,
H-1), 3.74 (s, 3H, CO2CH3), 3.56 (dm, 1H, J4,8 ) 6.8 Hz, H-4),
3.42 (ddd, 1H, J1,6 ) 3.9 Hz, J5endo,6 ) 5.9 Hz, J5exo,6 ) 9.0 Hz,
H-6), 2.11-2.20 (m, 2H, H-5); 13C NMR δ 171.4 (C-3), 170.4
(CO2CH3), 132.7 (C-8), 119.1 (C-7), 80.8 (C-1), 53.0 (CO2CH3),
43.6 (C-4), 42.8 (C-6), 23.8 (C-5).
Acknowledgment. We thank the Council for As-
sisting Refugee Academics (CARA) for financial support
(to A.N.).
Methyl 7-bromo-3-oxo-2-oxabicyclo[2.2.2]oct-7-ene-
5
exo-carboxylate: 1H NMR δ 6.66 (dd, 1H, J1,8 ) 2.5 Hz, J4,8
) 6.9 Hz, H-8), 5.20 (m, 1H, H-1), 3.81 (dd, J4,5 ) 2.3 Hz, J4,8
) 6.9 Hz, H-4), 3.76 (s, 3H, CO2CH3), 2.83 (ddd, 1H, J4,5 ) 2.3
Hz, J5,6exo ) 5.3 Hz, J5,6endo ) 10.8 Hz, H-5), 2.52 (ddd, 1H,
J1,6exo ) 3.9 Hz, J5,6exo ) 5.3 Hz, J6endo,6exo ) 14.0 Hz, H-6exo),
Supporting Information Available: Experimental pro-
cedures and characterization of all previously unreported
compounds; drawings, crystal data, and coordinates of all
crystal structures in pdb format; and coordinates of all
transition states in pdb format and absolute energies of all
transition states. This material is available free of charge via
2.19 (ddd, 1H, J1,6endo ) 1.7 Hz, J5,6endo ) 10.8 Hz, J6endo,6exo
)
14.0 Hz, H-6endo); 13C NMR δ 170.4 (CO2CH3), 168.9 (C-3), 130.5
(C-8), 123.5 (C-7), 80.8 (C-1), 53.4 (CO2CH3), 45.8 (C-4), 39.3
(C-5), 29.7 (C-6); IR 2978, 2924, 2846, 1773, 1734, 1437, 1353,
1265, 1207, 1132, 1009, 801, 737 cm-1; m/z 263 (49, MH+ for
81Br), 261 (49, MH+ for 79Br), 231 [11, (M+ for 81Br-OMe)],
JO048213K
J. Org. Chem, Vol. 70, No. 4, 2005 1133