Journal Information
Journal ID (publisher-id): chemical
Title: Journal of the Korean Chemical Society
Translated Title (ko): 대한화학회지
ISSN (print): 1017-2548
ISSN (electronic): 2234-8530
Publisher: Korean Chemical Society대한화학회
INTRODUCTION▼
The butenolide ring is important molecular skeleton that is widespread in natural products and complex heterocyclic synthetic compounds.1 Owing to its prevalence and significance, the butenolide scaffold has continuously attracted attention from a medicinal point of view. Therefore, the development of synthetic strategies for useful and more complex molecules containing the butenolide skeleton remains an active area of research in the field of the organic chemistry.2
The vinylogous Mannich-type reaction of imines with trimethylsiloxyfuran is a useful means of for the construction of alkylamine-substituted γ-butenolide derivatives.3 A wide range of metal complex catalysts and organocatalysts has been developed for the catalytic Mannich-type reaction of trimethylsiloxyfuran with imines such as aldimines,3a−c ketimines,3d,3f and isatin-derived ketimines.3e,3g
Recently, we reported the organocatalytic asymmetric aza-Friedel‒Crafts reaction of cyclic N-sulfimines with indoles and pyrroles using a chiral Brønsted acid as an organocatalyst. 4 Phosphoric acid (PA) has recently been recognized as a powerful chiral Brønsted acid catalyst for various asymmetric reactions.5 The enantioselective aza-Friedel‒Crafts reaction of cyclic N-sulfimines with indoles using PA2 as a catalyst at −40 ℃ afforded chiral 3-indolyl sulfamidate derivatives in good yields and with high enantioselectivities (up to 97% ee; Scheme 1(1)). The enantioenriched 3-pyrrolyl sulfamate derivatives were also obtained in the aza-Friedel‒Crafts reaction of cyclic N-sulfimines with pyrroles using PA6 as a catalyst in m-xylene at −40 ℃ (Scheme 1(2)). We were interested in further expanding these addition reactions with cyclic N-sulfimines using chiral PA as the organocatalysts. Thus, we focused our attention on the application of chiral PA catalysts to the vinylogous Mannich-type reaction involving a trimethylsiloxyfuran (Scheme 1(3)). We also report the first direct Mannich-type reaction of cyclic N-sulfimines with pyrazolin-5-one using a PA catalyst to obtain pyrazole containing sulfamidates (Scheme 1(4)).
Pyrazoles and pyrazolones are important classes of five-membered aza-heterocycles that are found in natural products and pharmaceutically relevant molecules.6 The pyrazolone moiety shows significant pharmacological activities in various synthetic compounds. Hence, much effort has been undertaken to develop synthetic methods toward new pyrazoles and pyrazolone-containing heterocyclic compounds.7
EXPERIMENTAL▼
General Procedures
Organic solvents were distilled prior to use. Organic solutions were concentrated under reduced pressure using a rotary evaporator. Chromatographic purification of products was accomplished using forced-flow chromatography on ICN 60 32-64 mesh silica gel 63. Thin-layer chromatography (TLC) was performed on EM Reagents 0.25 mm silica gel 60-F plates. Developed chromatograms were visualized by fluorescence quenching and with anisaldehyde stain. 1H and 13C NMR spectra were recorded (400 MHz for 1H and 100 MHz for 13C), and were internally referenced to residual protio solvent signals. Data for 1H NMR are reported as follows: chemical shift (δ ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet), coupling constant (Hz) and integration. Data for 13C NMR are reported in terms of chemical shift. IR spectra were recorded on an FT-IR spectrometer and are reported in wave numbers. High-resolution mass spectroscopy (HRMS) was performed by electron impact (EI).
General Procedure for the Catalytic Vinylogous Mannich-Type Reaction of Cyclic N-Sulfimines with 2-Trimethylsiloxyfuran
To a solution of cyclic N-sulfimine 1 (0.1 mmol) in toluene (0.5 mL) was added catalyst PA2 (0.01 mmol). The solution was stirred at room temperature for 10 min, and then 2-trimethylsiloyfuran 2 (0.2 mmol) was added in one portion. The reaction mixture was stirred at same temperature until cyclic N-sulfimine 1 was complete consumed, as determined by TLC. Then, the resulting mixture was diluted with water and extracted with CH2Cl2. The combined organic layer was washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The crude residue was purified by flash column chromatography with EtOAc/hexanes as eluent to afford desired product 3.
4-(5-Oxo-2H-fur-2-yl)-3,4-dihydro-1,2λ6,3-benzoxathiazine-2,2-dione (3a). White solid; m.p. 157−160 ℃; 1H NMR (400 MHz, CD3OD) δ 7.84 (dd, J = 5.8, 1.5 Hz, 1H), 7.61 (d, J = 7.6 Hz, 1H), 7.43 (td, J = 8.0, 1.1 Hz, 1H), 7.28 (td, J = 7.7, 1.1 Hz, 1H), 7.08 (dd, J = 8.3, 1.0 Hz, 1H), 6.32 (dd, J = 5.8, 2.0 Hz, 1H), 5.68 (dt, J = 7.8, 1.7 Hz, 1H), 4.78 (d, J = 7.8 Hz, 1H); 13C NMR (100 MHz, CD3OD) δ 173.03, 155.00, 151.29, 129.98, 128.16, 124.99, 122.27, 118.76, 118.33, 83.76, 58.13; IR (film) 3331, 3181, 2923, 2851, 1742, 1583, 1454, 1428, 1364, 1105, 1071, 1035 cm−1; HRMS (EI) m/z calcd for [M]+ C11H9NO5S: 267.0201 Found: 267.0231.
6-Methyl-4-(5-oxo-2H-fur-2-yl)-3,4-dihydro-1,2λ6,3-benzoxathiazine-2,2-dione (3b). White solid; m.p. 85−88 ℃; 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 5.5 Hz, 1H), 7.30 (s, 1H), 7.18 (d, J = 8.6 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H), 6.24 (d, J = 4.7 Hz, 1H), 5.92 (d, J = 6.9 Hz, 1H), 5.54 (d, J = 7.1 Hz, 1H), 4.68 (t, J = 7.0 Hz, 1H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 172.90, 154.58, 148.71, 135.90, 131.22, 128.09, 123.14, 118.80, 117.48, 83.91, 58.71, 20.88; IR (film) 3302, 3118, 1747, 1600, 1491, 1431, 1373, 1202, 1176, 1115, 1088, 1044 cm−1; HRMS (EI) m/z calcd for [M]+ C12H11NO5S: 281.0358 Found: 281.0351.
8-Methoxy-4-(5-oxo-2H-fur-2-yl)-3,4-dihydro-1,2λ6,3-benzoxathiazine-2,2-dione (3c). White solid; m.p. 84−87 ℃; 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 5.7 Hz, 1H), 7.17 (t, J = 8.1 Hz, 1H), 7.06 (d, J = 7.8 Hz, 1H), 6.96 (d, J = 8.0 Hz, 1H), 6.23 (d, J = 4.5 Hz, 1H), 6.00 (d, J = 7.1 Hz, 1H), 5.55 (d, J = 7.4 Hz, 1H), 4.74 (t, J = 7.2 Hz, 1H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 172.78, 154.46, 148.80, 140.47, 125.58, 123.18, 118.91, 118.60, 112.85, 83.72, 58.78, 56.30; IR (film) 3215, 2921, 2852, 1789, 1746, 1582, 1479, 1435, 1374, 1317, 1273, 1180, 1156, 1082, 1043 cm−1; HRMS (EI) m/z calcd for [M]+ C12H13NO6S: 297.0307 Found: 297.0307.
6-Fluoro-4-(5-oxo-2H-fur-2-yl)-3,4-dihydro-1,2λ6,3-benzoxathiazine-2,2-dione (3d). White solid; m.p. 161−164 ℃; 1H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 7.81 (dd, J = 5.7, 1.4 Hz, 1H), 7.49 (dd, J = 9.3, 2.9 Hz, 1H), 7.36 (dd, J = 8.0, 2.9 Hz, 1H), 7.30–7.24 (m, 1H), 6.44 (dd, J = 5.7, 1.9 Hz, 1H), 5.75 (d, J = 6.8 Hz, 1H), 5.09 (d, J = 6.7 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ 172.64, 158.83 (d, J1 = 242.0 Hz), 155.41, 147.43, 123.07, 120.92 (d, J3 = 8.9 Hz), 120.84 (d, J3 = 8.5 Hz), 117.66 (d, J2 = 23.8 Hz), 115.41 (d, J2 = 25.7 Hz), 82.88, 57.02; IR (film) 3114, 2924, 2853, 1738, 1598, 1486, 1421, 1374, 1286, 1258, 1194, 1100, 1088, 1012 cm−1; HRMS (EI) m/z calcd for [M]+ C11H8FNO5S: 285.0107 Found: 285.0117.
6-Chloro-4-(5-oxo-2H-fur-2-yl)-3,4-dihydro-1,2λ6,3-benzoxathiazine-2,2-dione (3e). White solid; m.p. 172−177 ℃; 1H NMR (400 MHz, DMSO-d6) δ 9.24 (s, 1H), 7.85 (d, J = 5.7 Hz, 1H), 7.69 (s, 1H), 7.54 (d, J = 8.6 Hz, 1H), 7.25 (d, J = 8.9 Hz, 1H), 6.44 (d, J = 5.2 Hz, 1H), 5.73 (d, J = 6.9 Hz, 1H), 5.07 (d, J = 7.0 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ 172.60, 155.48, 150.06, 130.59, 129.54, 128.60, 123.09, 121.05, 120.90, 82.87, 57.00; IR (film) 3169, 2918, 2851, 1758, 1748, 1476, 1444, 1290, 1260, 1193, 1166, 1-45, 1024 cm−1; HRMS (EI) m/z calcd for [M]+ C11H8ClNO5S: 299.0019 Found: 299.0014.
6-Bromo-4-(5-oxo-2H-fur-2-yl)-3,4-dihydro-1,2λ6,3-benzoxathiazine-2,2-dione (3f). White solid; m.p. 205−208 ℃; 1H NMR (400 MHz, CD3OD) δ 7.88 (dd, J = 5.8, 1.5 Hz, 1H), 7.80 (d, J = 1.7 Hz, 1H), 7.59 (dd, J = 8.8, 2.0 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 6.36 (dd, J = 5.8, 2.0 Hz, 1H), 5.67 (dt, J = 8.1, 1.8 Hz, 1H), 4.77 (d, J = 8.1 Hz, 1H); 13C NMR (100 MHz, CD3OD) δ 172.81, 154.83, 150.47, 132.99, 131.03, 122.41, 120.93, 120.26, 117.34, 83.42, 57.84; IR (film) 3117, 2920, 2851, 1746, 1474, 1441, 1389, 1376, 1312, 1266, 1170, 1107, 1082, 1046, 1024 cm−1; HRMS (EI) m/z calcd for [M]+ C11H8BrNO5S: 344.9307 Found: 344.9285.
6,8-Dibromo-4-(5-oxo-2H-fur-2-yl)-3,4-dihydro-1,2λ6,3-benzoxathiazine-2,2-dione (3g). White solid; m.p. 92−95 ℃; 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 2.0 Hz, 1H), 7.78 (d, J = 1.5 Hz, 1H), 7.68 (d, J = 1.8 Hz, 1H), 6.32 (dd, J = 5.8, 1.8 Hz, 1H), 6.00 (s, 1H), 5.57 (d, J = 8.0 Hz, 1H), 4.66 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 172.38, 154.21, 147.03, 136.80, 130.06, 123.58, 121.30, 118.58, 113.72, 83.28, 58.86; IR (film) 3095, 2923, 2852, 1787, 1748, 1555, 1444, 1379, 1193, 1159, 1090, 1047, 1021 cm−1; HRMS (EI) m/z calcd for [M]+ C11H7Br2NO5S: 422.8412 Found: 422.8398.
General Procedure for the Catalytic Mannich-Type Reaction of Cyclic N-Sulfimines with pyrazolin-5-one
To a solution of cyclic N-sulfimine 1 (0.1 mmol) in toluene (0.5 mL) was added catalyst PA2 (0.01 mmol). The solution was stirred at room temperature for 10 min, and then 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one 4 (0.2 mmol) was added in one portion. The reaction mixture was stirred at same temperature until cyclic N-sulfimine 1 was complete consumed, as determined by TLC. Then, the resulting mixture was diluted with water and extracted with CH2Cl2. The combined organic layer was washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The crude residue was purified by flash column chromatography with EtOAc/hexanes as eluent to afford desired product 5.
4-(3-Hydroxy-5-methyl-2-phenyl-2H-pyrazol-4-yl)-3,4-dihydro-1,2λ6,3-benzoxathiazine-2,2-dione (5a). White solid; m.p. 124−127 ℃; 1H NMR (400 MHz, DMSO-d6) δ 8.58 (d, J = 6.8 Hz, 1H), 7.76 (d, J = 7.8 Hz, 2H), 7.47 (t, J = 7.5 Hz, 2H), 7.38 (t, J = 7.3 Hz, 1H), 7.28–7.07 (m, 4H), 5.94 (s, 1H), 1.81 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 151.35, 148.46, 138.15, 129.81, 129.44, 128.27, 125.80, 125.72, 122.46, 120.55, 118.73, 100.27, 79.65, 51.66, 13.21; IR (film) 2955, 2924, 2854, 1726, 1594, 1575, 1497, 1482, 1451, 1409, 1371, 1273, 1247, 1191, 1072, 1021 cm−1; HRMS (EI) m/z calcd for [M]+ C17H15N3O4S: 357.0783 Found: 357.0786.
4-(3-Hydroxy-5-methyl-2-phenyl-2H-pyrazol-4-yl)-6-methyl-3,4-dihydro-1,2λ6,3-benzoxathiazine-2,2-dione (5b). White solid; m.p. 148−151 ℃; 1H NMR (400 MHz, CDCl3) δ 7.37–7.06 (m, 6H), 7.00 (d, J = 8.3 Hz, 1H), 6.78 (d, J = 8.3 Hz, 1H), 6.60 (s, 1H), 5.55 (s, 1H), 2.19 (s, 3H), 1.96 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.53, 148.99, 146.17, 135.19, 134.84, 130.34, 128.97, 127.08, 126.72, 120.95, 120.74, 118.27, 100.83, 52.63, 20.81, 10.77; IR (film) 2955, 2924, 2854, 1593, 1567, 1487, 1406, 1369, 1308, 1247, 1205, 1174, 1105, 1028 cm−1; HRMS (EI) m/z calcd for [M]+ C18H17N3O4S: 371.0940 Found: 371.0970.
4-(3-Hydroxy-5-methyl-2-phenyl-2H-pyrazol-4-yl)-7-methyl-3,4-dihydro-1,2λ6,3-benzoxathiazine-2,2-dione (5c). White solid; m.p. 127-131 ℃; 1H NMR (400 MHz, CDCl3) δ 7.39–7.01 (m, 6H), 6.84 (d, J = 7.9 Hz, 1H), 6.73 (s, 1H), 6.66 (d, J = 7.9 Hz, 1H), 5.54 (s, 1H), 2.27 (s, 3H), 1.93 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.43, 150.89, 146.21, 140.24, 134.86, 129.00, 126.76, 126.18, 120.82, 119.14, 118.77, 118.22, 100.79, 52.45, 20.98, 10.75; IR (film) 2954, 2922, 2853, 1594, 1574, 1497, 1409, 1370, 1307, 1250, 1192, 1101, 1023 cm−1; HRMS (EI) m/z calcd for [M]+ C18H17N3O4S: 371.0940 Found: 371.0929.
4-(3-Hydroxy-5-methyl-2-phenyl-2H-pyrazol-4-yl)-8-methoxy-3,4-dihydro-1,2λ6,3-benzoxathiazine-2,2-dione (5d). White solid; m.p. 117−119 ℃; 1H NMR (400 MHz, CDCl3) δ 7.35–7.07 (m, 6H), 6.8 (d, J = 8.5 Hz, 1H), 6.75 (d, J = 7.5 Hz, 1H), 6.28 (s, 1H), 5.51 (s, 1H), 3.64 (s, 3H), 1.93 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.62, 156.58, 146.30, 144.90, 134.87, 129.07, 126.84, 122.37, 120.73, 119.44, 114.05, 112.54, 101.11, 55.74, 52.70, 10.78; IR (film) 2921, 2851, 1595, 1567, 1486, 1413, 1370, 1279, 1202, 1167, 1109, 1026 cm−1; HRMS (EI) m/z calcd for [M]+ C18H17N3O5S: 387.0889 Found: 387.0878.
6-Fluoro-4-(3-hydroxy-5-methyl-2-phenyl-2H-pyrazol-4-yl)-3,4-dihydro-1,2λ6,3-benzoxathiazine-2,2-dione (5e). White solid; m.p. 198−201 ℃; 1H NMR (400 MHz, DMSO-d6) δ 8.66 (s, 1H), 7.76 (d, J = 7.8 Hz, 2H), 7.63–7.12 (m, 5H), 6.95 (d, J = 7.7 Hz, 1H), 5.91 (s, 1H), 1.88 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 159.13 (d, J1 = 242.2 Hz), 148.44, 147.48, 138.06, 129.43, 125.82, 124.52, 124.47, 121.28, 120.70 (d, J3 = 8.3 Hz), 116.85 (d, J2 = 23.8 Hz), 114.54 (d, J2 = 24.9 Hz), 100.02, 51.68, 13.21; IR (film) 3314, 3077, 2920, 1622, 1594, 1584, 1501, 1488, 1423, 1403, 1370, 1278, 1255, 1210, 1164, 1104, 1034 cm−1; HRMS (EI) m/z calcd for [M]+ C17H14FN3O4S: 375.0689 Found: 375.0691.
6-Chloro-4-(3-hydroxy-5-methyl-2-phenyl-2H-pyrazol-4-yl)-3,4-dihydro-1,2λ6,3-benzoxathiazine-2,2-dione (5f). White solid; m.p. 189−191 ℃; 1H NMR (400 MHz, DMSO-d6) δ 8.72 (s, 1H), 7.74 (dd, J = 8.6, 1.0 Hz, 2H), 7.53–7.34 (m, 3H), 7.25 (dd, J = 15.9, 8.0 Hz, 2H), 7.13 (s, 1H), 5.91 (s, 1H), 1.87 (s, 3H); 13C NMR (100 MHz, DMSOd6) δ 161.53, 149.56, 147.77, 137.47, 129.21, 128.93, 128.85, 127.14, 125.24, 123.95, 120.22, 118.72, 100.80, 50.94, 13.14; IR (film) 3323, 1919, 1851, 1594, 1583, 1500, 1471, 1403, 1364, 1278, 1251, 1212, 1191, 1168, 1107, 1030 cm−1; HRMS (EI) m/z calcd for [M]+ C17H14ClN3O4S: 391.0394 Found: 391.0406.
6-Bromo-4-(3-hydroxy-5-methyl-2-phenyl-2H-pyrazol-4-yl)-3,4-dihydro-1,2λ6,3-benzoxathiazine-2,2-dione (5g). White solid; m.p. 119−122 ℃; 1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 1H),7.76 (d, J = 7.9 Hz, 2H), 7.58 (d, J = 8.1 Hz, 1H), 7.47 (t, J = 7.6 Hz, 2H), 7.25 (d, J = 9.8 Hz, 2H), 7.16 (d, J = 8.7 Hz, 1H), 5.94 (s, 1H), 1.89 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 150.66, 148.24, 138.07, 132.67, 130.60, 129.42, 125.83, 124.89, 121.10, 120.56, 117.42, 99.73, 79.64, 51.45, 12.90; IR (film) 2921, 2852, 1593, 1573, 1497, 1468, 1392, 1372, 1261, 1208, 1188, 1167, 1110, 1078, 1032 cm−1; HRMS (EI) m/z calcd for [M]+ C17H14BrN3O4S: 434.9888 Found: 434.9893.
6,8-Dibromo-4-(3-hydroxy-5-methyl-2-phenyl-2H-pyrazol-4-yl)-3,4-dihydro-1,2λ6,3-benzoxathiazine-2,2-dione (5g). White solid; m.p. 190−192 ℃; 1H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 1H), 7.98 (s, 1H), 7.73 (d, J = 7.9 Hz, 2H), 7.47 (t, J = 7.9 Hz, 2H), 7.26 (dd, J = 14.3, 6.6 Hz, 2H), 5.93 (s, 1H), 1.93 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 148.25, 147.55, 138.15, 135.17, 130.25, 129.44, 126.42, 125.84, 120.90, 120.41, 117.52, 113.03, 100.03, 51.81, 13.48; IR (film) 3256, 2920, 1597, 1572, 1502, 1441, 1411, 1375, 1312, 1252, 1196, 1152, 1109, 1028 cm−1; HRMS (EI) m/z calcd for [M]+ C17H13Br2N3O4S: 512.8994 Found: 512.9003.
RESULTS AND DISCUSSION▼
Based on our previous asymmetric catalytic aza-Friedel-Crafts reaction of cyclic N-sulfimines,4 we first evaluated a chiral PA (Fig. 1) as a catalyst for the asymmetric Mannich-type reaction of benzoxathiazine 2,2-dioxide 1a with 2-trimethyloxyfuran 2. This Mannich-type reaction was conducted in toluene at room temperature in the presence of 10 mol% PA1. The reaction proceeded smoothly to give desired product 3a in 55% yield and with 5:1 dr and 53:47 er (Table 1, entry 1). Encouraged by this result, we continued to test various BINOL-derived PAs (Table 1, entries 2‒11). However, despite of the application of various PA catalysts, asymmetric catalytic reaction did not give satisfactory results. The highest enantioselectivity with 58:42 er was obtained when using PA3 (Table 1, entry 3). However, the Mannich-type reaction of 1a with 2 provided the desired sulfamidate γ-butenolide 3a in good yields and high diastereoselectivities under these reaction conditions. Therefore, we focused on substrate generality with respect to the cyclic N-sulfimine component in this Mannich-type reaction by considering only yields and diastereoselectivities. PA2 was chosen as the catalyst from the viewpoints of reactivity and stereoselectivity.
Table1.
Screen of chiral phosphoric acid catalysts for the asymmetric Mannich reaction of cyclic N-sulfimine 1a with 2-trimethyloxyfuran 2.a
The influence of the electronic and steric properties of the substituents on the phenyl ring of the N-sulfimines were exploited (Scheme 2). Although sulfamidate γ-butenolide products were obtained in good yields, the reaction efficiency and diastereoselectivity were somewhat influenced by the electronic nature, bulkiness, and position of the substituent on the phenyl ring of the N-sulfimines. Cyclic N-sulfimines bearing electron-withdrawing groups were more reactive than those bearing electron-donating groups (Scheme 2, 3b vs. 3d‒3f). Cyclic N-sulfimines bearing an electrondonating group at the 6-position exhibited lower reactivity but higher reaction yield than those bearing electrondonating groups at the 8-position (Scheme 2, 3b vs. 3c). In particular, the cyclic N-sulfimine with a bromine group at the 6-position showed the highest diastereoselectivity (7:1 dr). The presence of an additional halogen group in the phenyl ring led to slightly better reactivity and reaction yield, but did not affect the diastereoselectivity (Scheme 2, 3f vs. 3g).
Next, the Mannich-type reaction of cyclic N-sulfimines with pyrazolin-5-one was attempted. We investigated the scope of the Mannich-type reaction of 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one 4 with various cyclic N-sulfimines 1 in the presence of 10 mol% PA2 in toluene at room temperature. The results are summarized in Scheme 3. Cyclic N-sulfimines bearing a diverse range of electron-donating and electron-withdrawing substituents on the phenyl ring provided the desired sulfamidate products in good to high yields (65‒94%). The presence of an additional halogen substituent in the phenyl ring slightly increased the reactivity in this reaction (Scheme 3, 5g vs. 5h).
CONCLUSION▼
In summary, we have developed a highly efficient Mannich-type reaction of 2-trimethylsiloxyfuran and pyrazolin-5-one with cyclic N-sulfimines using PA as an organocatalyst. The desired sulfamidate γ-butenolide derivatives were obtained in good yields and high diastereoselectivities (up to 90% yield and 7:1 dr). The Mannich-type reaction of pyrazolin-5-one with cyclic N-sulfimine provided access to sulfami-date derivatives in good to high yields (up to 94% yield). Current work is still focused on the asymmetric version of these Mannich-type reaction.