160 Letters in Organic Chemistry, 2011, Vol. 8, No. 3
Rodríguez-Lucena et al.
[M+Na]+, 233.5 [M+H]+; HRMS (ESI): [M+Na]+, found
255.041. C8H12N2NaO4S requires 255.042.
3.48 (1H, dd, J 11.7, 4.2 Hz, H-2b), 3.39–3.32 (1H, m, H-
5a), 3.28 (1H, dt, J 9.6, 7.8 Hz, H-5b), 2.43 (3H, s, CH3),
2.14–2.09 (2H, m, H-4); 13C NMR (75.5 MHz, Acetone-d6)
ꢀ144.6, 134.8, 130.6, 128.5, 80.0, 54.5, 46.7, 32.6, 21.4; m/z
(ESI) 343.0 [M+Na]+; HRMS (ESI): [M+Na]+, found
343.036. C11H16N2NaO5S2 requires 343.039.
(±)-(1R*, 6R*)-2,9-Diaza-9-carbobenzoxy-4-oxa-3-thia-
bicyclo[4.3.0]nonane-3,3-dioxide (16)
Compound 8 (722 mg, 2.30 mmol) was treated during 3 h
as described in the general intramolecular C-H amination
procedure using MgO (213 mg, 5.29 mmol), PhI(OAc)2 (815
mg, 2.53 mmol) and Rh2(OAc)4 (51 mg, 0.12 mmol). The
crude mixture was purified by flash chromatography (1:1 ꢀ
2:1 EtOAc/Pet. Ether) to give 16 as a white crystalline solid
(618 mg, 86%); ꢀmax (neat) 3160, 1690, 1424, 1350, 1190
cmꢁ1; 1H NMR (400 MHz, 353 K, DMSO-d6) ꢀ7.52 (1H, bs,
NH), 7.40–7.31 (5H, m, Ph), 5.35 (1H, bd, J 4.8 Hz, H-1),
5.17 (1H, d, J 12.8 Hz, PhCHa), 5.13 (1H, d, J 12.8 Hz,
PhCHb), 4.70 (1H, dd, J 12.0, 3.6 Hz, H-5a), 4.46 (1H, dd, J
12.0, 1.6 Hz, H-5b), 3.53 (1H, td, J 10.4, 2.4 Hz, H-8a), 3.38
(1H, dt, J 10.4, 8.0 Hz, H-8b), 2.42–2.33 (1H, m, H-6), 2.24–
2.13 (1H, m, H-7a), 2.06–1.99 (1H, m, H-7b); 13C NMR
(100.6 MHz, 353 K, DMSO-d6) ꢀ152.7, 136.2, 127.7, 127.2,
126.8, 69.6, 69.5, 65.8, 44.5, 34.5, 23.2; m/z (ESI) 335.1
[M+Na]+; HRMS (ESI): [M+Na]+, found 335.066.
C13H16N2NaO5S requires 355.067.
N-[1-(Hydroxycyclopropyl)-carbonyl]-pyrrolidine (12)
To a solution of carboxylic acid 13 (1.0 g, 9.80 mmol) in
dichloromethane (25 mL), were added pyrrolidine (650 μL,
7.79 mmol), HOBt (1.16 g, 8.58 mmol), N-
methylmorpholine (1.8 mL, 16.37 mmol), and EDCI (2.24 g,
11.7 mmol) at room temperature. The solution was stirred
for 16 h. The reaction was quenched with a solution of
saturated NH4Cl and diluted with water and dichloro-
methane. The mixture was extracted with dichloromethane
three times. The combined organic layer was dried over
MgSO4, filtered and the solvent evaporated. The resulting
residue was purified by flash chromatography (95:5
CH2Cl2/Acetone) to yield 12 as a solid (1.05 g, 87%);1H
NMR (400 MHz, Acetone-d6) ꢀ5.16 (1H, s, OH), 3.85-3.77
(2H, m, H-2), 3.38-3.30 (2H, m, H-5), 1.92-1.84 (2H, m, H-
3), 1.84-1.76 (2H, m, H-4), 1.25-1.17 (2H, m, CH cyclo-
propyl), 0.83-0.75 (2H, m, CH cyclopropyl); 13C NMR (62.9
MHz, Acetone-d6) ꢀ171.2, 56.6, 47.6, 47.3, 27.0, 24.2, 14.7.
(±)-(1R*, 6R*)-2,9-Diaza-4-oxa-3-thia-9-(toluene-4-
sulfonyl)-bicyclo[4.3.0]nonane-3,3-dioxide (17)
N-[1-(Sufamoyloxycyclopropyl)-carbonyl]-pyrrolidine (14)
Compound 9 (100 mg, 0.30 mmol) was treated during 2 h
as described in the general intramolecular C-H amination
procedure using MgO (28 mg, 0.69 mmol), PhI(OAc)2 (106
mg, 0.33 mmol) and Rh2(OAc)4 (7 mg, 15 μmol). The crude
mixture was purified by flash chromatography (1:1
EtOAc/Pet. Ether) to give 17 as a white crystalline solid (82
mg, 83%). As an alternative to flash chromatography, the
compound may be purified by recrystallisation from hot
methanol (62% yield); ꢀmax (neat) 3207, 1426, 1335, 1189,
To a solution of 12 (1.05 g, 6.77 mmol) in N,N-
dimethylacetamide (11 mL), was added sulfamoyl chloride
(2.33 g, 20.17 mmol) at 0 ºC. The reaction was stirred at
room temperature for 16 h. To the reaction mixture was
added water and ethyl acetate. The organic layer was
separated and the aqueous layer extracted twice with ethyl
acetate. The combined organic layer was dried over MgSO4,
filtered and the solvent evaporated under reduced pressure.
The residue was purified by flash chromatography (99:1 ꢀ
90:10 CH2Cl2/Acetone) to afford 14 as a solid (1.34 g,
1
1161 cmꢁ1; H NMR (300 MHz, DMSO-d6) ꢀ7.86 (1H, d, J
7.5 Hz, NH), 7.75, 7.44 (4H, 2d, J 8.1, p-Tol), 5.22 (1H, dd,
J 7.5, 4.5 Hz, H-1), 4.58 (1H, dd, J 12.3, 3.3 Hz, H-5a), 4.15
(1H, d, J 12.3 Hz, H-5b), 3.40 (1H, t, J 9.3 Hz, H-8a), 3.09
(1H, dt, J 9.3, 7.5 Hz, H-8b), 2.40 (3H, s, CH3), 2.22–2.09
(1H, m, H-7a), 1.98–1.80 (2H, m, H-6, H-7b); 13C NMR
(75.5 MHz, DMSO-d6) ꢀ143.7, 134.9, 129.9, 127.2, 71.9,
69.6, 46.5, 35.1, 23.9, 21.0; m/z (ESI) 355.0 [M+Na]+;
HRMS (ESI): [M+Na]+, found 355.035. C12H16N2NaO5S2
requires 355.039.
1
84%);ꢀmax (neat) 3406, 1633, 1462, 1373, 1136 cmꢁ1; H
NMR (400 MHz, Acetone-d6) ꢀ6.93 (2H, s, NH2), 3.72 (2H,
t, J 6.4 Hz, H-2), 3.36 (2H, t, J 6.8 Hz, H-5), 1.95-1.87 (2H,
m, H-3), 1.85-1.77 (2H, m, H-4), 1.41-1.33 (2H, m, CH
cyclopropyl), 1.28-1.20 (2H, m, CH cyclopropyl); 13C NMR
(62.9 MHz, Acetone-d6) ꢀ166.4, 63.3, 47.3, 47.2, 26.7, 24.1,
11.7; m/z (ESI) 257.5 [M+Na]+, 235.0 [M+H]+; HRMS
(ESI): [M+Na]+, found 257.057. C8H14N2NaO4S requires
257.057.
(1R, 5R)-4,6-Diaza-2-oxa-3-thia-6-(toluene-4-sulfonyl)-
bicyclo[3.3.0]octane-3,3-dioxide (18)
(±)-Spiro[cyclopropane-1,4’(5’H)-[1H]pyrrolo[2,1-d][1,2,3,
5]oxathiadiazepin]-5’-one, tetrahydro-2’,2-dioxide (15)
Compound 11 (364 mg, 1.14 mmol) was treated during
1.5 h as described in the general intramolecular C-H
amination procedure using MgO (105 mg, 2.61 mmol),
PhI(OAc)2 (403 mg, 1.25 mmol) and Rh2(OAc)4 (25 mg, 57
μmol). The crude mixture was purified by flash
chromatography (2:1 EtOAc/Pet. Ether) to give 18 as a white
solid (346 mg, 95%); [ꢁ]D20-107.5 (c 1.0, Acetone); ꢀmax
Compound 14 (270 mg, 1.15 mmol) was treated during
16 h as described in the general intramolecular C-H
amination procedure using MgO (107 mg, 2.65 mmol),
PhI(OAc)2 (420 mg, 1.30 mmol) and Rh2(OAc)4 (25 mg, 57
μmol). The crude mixture was purified by flash
chromatography (2:8 CH3CN/CH2Cl2) to give 15 as a solid
(230 mg, 86%);ꢀmax (neat) 3442, 1628, 1466, 1373, 1192,
1
(neat) 3234, 1337, 1195, 1154 cmꢁ1; H NMR (300 MHz,
1
1148 cmꢁ1; H NMR (400 MHz, Acetone-d6) ꢀ8.06 (1H, s,
Acetone-d6) ꢀ7.81 (2H, d, J 8.1, p-Tol), 7.72 (1H, bd, J 5.4
Hz, NH), 7.42 (2H, d, J 8.1, p-Tol), 5.95 (1H, bt, J 5.4 Hz,
H-5), 5.51 (1H, t, J 5.4 Hz, H-1), 3.65 (1H, ddd, J 10.5, 8.1,
1.5 Hz, H-7a), 3.48 (1H, td, J 10.5, 5.7 Hz, H-7b), 2.43 (3H,
s, CH3), 2.22 (1H, bdd, J 14.4, 5.7 Hz, H-8a), 2.17–2.08 (1H,
m, H-8b); 13C NMR (75.5 MHz, Acetone-d6) ꢀ144.8, 137.4,
NH), 5.47 (1H, t, J 6.0 Hz, H-2), 3.55-3.46 (2H, m, H-5),
2.43-2.35 (1H, m, H-3a), 2.02-1.85 (3H, m, H-3b, H-4),
1.60-1.47 (2H, m, CH cyclopropyl), 1.37-1.27 (2H, m, CH
cyclopropyl); 13C NMR (62.9 MHz, Acetone-d6) ꢀ166.8,
68.5, 64.1, 48.0, 33.5, 21.7, 15.6, 14.8; m/z (ESI) 255.5