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M. Poornachandran, R. Raghunathan / Tetrahedron: Asymmetry 19 (2008) 2177–2183
4.6.5. (3aR,6S,6aR)-cis-1-(4-Bromo)-phenyl-5-tosyl-6-benzyl-
octahydropyrrolo[3,4-b]pyrrole, 8e
2.45 (s, 3H), 2.65–2.79 (m, 3H), 3.05–3.08 (m, 1H), 3.25–3.31 (m,
2H), 3.46–3.49 (m, 1H), 3.66–3.73 (m, 1H), 3.74–3.78 (dd, 2H,
J = 2.9, 9.8 Hz), 4.52 (s, 1H), 6.97–7.74 (m, 13H, Ar-H); 13C NMR
(CDCl3, 100 MHz): d 21.57, 21.89, 27.79, 41.85, 42.37, 46.47,
51.37, 64.04, 65.19, 108.12, 114.98, 126.12, 127.15, 128.46,
129.89, 129.65, 130.86, 133.11, 137.76, 141.87, 143.43, and
144.76; Mass spectrum (EI, 70 eV): m/z, 504.71 (M+). Anal. Calcd
for C29H32N2O2S2: C, 69.01, H, 6.39, N, 5.55. Found: C, 69.07, H,
6.29, N, 5.50.
Colorless solid, 68% (0.348 g); ½a D29
ꢀ
¼ þ29:8 (c 1, CHCl3); Mp:
145–147 °C; IR (KBr): 1337 and 1166 cmꢁ1
;
1H NMR (CDCl3,
400 MHz): d 1.60–1.75 (m, 2H, CH2), 2.33 (s, 3H, Ar-CH3), 2.53–
2.85 (m, 3H), 3.24–3.28 (dd, 1H, J = 2.9, 10.0 Hz), 3.66–3.73 (m,
2H), 3.97–4.00 (dd, 1H, J = 2.9, 10.4 Hz), 5.43 (d, 2H, J = 8.7 Hz),
6.96–7.43 (m, 13H, Ar-H); 13C NMR (CDCl3, 100 MHz): d 21.46,
27.56, 41.49, 42.47, 46.84, 51.83, 64.84, 65.69, 108.18, 114.26,
126.82, 127.95, 128.20, 128.44, 129.65, 130.02, 131.07, 133.10,
137.56, 141.65, 143.04, and 144.30; Mass spectrum (EI, 70 eV):
m/z, 513.16 (M+). Anal. Calcd for C26H27BrN2O2S: C, 61.05, H,
5.32, N, 5.48. Found: C, 61.14, H, 5.24, N, 5.57.
4.7.3. (2S,3aR,4S,6aR,7aR)-cis-2-(p-Methoxy)-phenyl-4-benzyl-
5-N-(p-methyl)-benzenesulfonyl perhydrothiazolo[30,40-2,3]-
pyrrolo[4,5-c]pyrrole, 10c
Brownish viscous liquid, 65% (0.338 g); ½a D29
ꢀ
¼ ꢁ15:8 (c 1,
4.6.6. (3aR,6S,6aR)-cis-1-(4-Fluoro)-phenyl-5-tosyl-6-benzyl-
octahydropyrrolo[3,4-b]pyrrole, 8f
CHCl3); IR (KBr): 1336 and 1168 cmꢁ1 1H NMR (CDCl3,
;
400 MHz): d 1.68–1.73 (m, 1H), 1.80–1.85 (m, 1H), 2.46 (s, 3H),
2.65–2.77 (m, 3H), 3.04–3.07 (m, 1H), 3.20–3.30 (m, 2H), 3.45–
3.49 (m, 1H), 3.67–3.71 (m, 1H), 3.74–3.77 (dd, 2H, J = 2.9,
9.8 Hz), 3.79 (s, 3H, Ar-OMe), 4.54 (s, 1H), 6.98–7.80 (m, 13H, Ar-
H); 13C NMR (CDCl3, 100 MHz): d 21.67, 27.89, 37.67, 41.23,
42.65, 46.38, 51.73, 64.76, 65.91, 108.43, 114.59, 126.41, 127.01,
128.09, 129.98, 129.33, 130.09, 133.52, 137.34, 141.09, 143.09,
and 144.98; Mass spectrum (EI, 70 eV): m/z, 520.77 (M+). Anal.
Calcd for C29H32N2O3S2: C, 66.89, H, 6.19, N, 5.38. Found: C,
66.75, H, 6.27, N, 5.30.
Colorless solid, 71% (0.320 g); ½a D27
ꢀ
¼ þ2:5 (c 1, CHCl3); Mp:
148–150 °C; IR (KBr): 1337 and 1168 cmꢁ1
;
1H NMR (CDCl3, 400
MHz): d 1.64–1.75 (m, 2H, CH2), 2.34 (s, 3H, Ar-CH3), 2.59–2.86
(m, 3H), 3.25–3.28 (dd, 1H, J = 2.6, 10.4 Hz), 3.69–3.73 (m, 2H),
3.99–4.02 (dd, 1H, J = 2.8, 10.4 Hz), 5.51 (d, 2H, J = 8.0 Hz), 6.63–
7.44 (m, 13H, Ar-H); 13C NMR (CDCl3, 100 MHz): d 21.46, 27.55,
30.92, 41.59, 42.48, 47.29, 51.92, 65.05, 65.93, 113.14, 113.22,
114.76, 114.98, 127.07, 128.64, 129.34, 130.08, 133.95, 137.68,
142.01, 142.94, 153.84, and 156.17; Mass spectrum (EI, 70 eV):
m/z, 450.59 (M+). Anal. Calcd for C26H27FN2O2S: C, 69.31, H, 6.04,
N, 6.22. Found: C, 69.43, H, 6.10, N, 6.10.
4.7.4. (2S,3aR,4S,6aR,7aR)-cis-2-(p-Chloro)-4-benzyl-5-N-
(p-methyl)-benzenesulfonyl perhydrothiazolo[30,40-2,3]-
pyrrolo[4,5-c]pyrrole, 10d
4.7. Synthesis of enantiopure perhydrothiazolo[30,40-2,3]-
pyrrolo[4,5-c]pyrroles, 10a–f
Brownish viscous liquid, 70% (0.366 g); ½a D29
ꢀ
¼ ꢁ12:8 (c 1,
CHCl3); IR (KBr): 1338 and 1170 cmꢁ1
;
1H NMR (CDCl3,
A mixture of (S)-2-(N-allyl-N-tosylamino)-3-phenylpropanal 6
(1.0 mmol) and 2-aryl-thiazolidine-4-carboxylic acids 9a–f
(1.5 mmol) in 30 mL of dry toluene was refluxed under Dean–Stark
conditions until the completion of the reaction (2.5–4 h). The reac-
tion mixture was then concentrated under reduced pressure. The
concentrate was extracted with dichloromethane (2 ꢂ 20 mL) and
water (2 ꢂ 20 mL). The organic layer was washed with brine solu-
tion (2 ꢂ 20 mL), dried over anhydrous sodium sulfate, and con-
centrated in vacuum. The residue was then subjected to column
chromatography (silica gel, 100–200 mesh) with hexane–ethyl
acetate (8:2) to obtain the cycloadducts 10a–f, (2R,3aR,4S,6aR,7-
aR)-cis-2-aryl-4-benzyl-5-N-(p-methyl)-benzenesulfonyl-perhy-
drothiazolo[30,40-2,3]pyrrolo[4,5-c]pyrroles.
400 MHz): d 1.68–1.72 (m, 1H), 1.81–1.85 (m, 1H), 2.47 (s, 3H),
2.66–2.78 (m, 3H), 3.05–3.08 (m, 1H), 3.24–3.31 (m, 2H), 3.46–
3.49 (m, 1H), 3.66–3.70 (m, 1H), 3.75–3.79 (dd, 2H, J = 2.9,
9.8 Hz), 4.50 (s, 1H), 6.87–7.79 (m, 13H, Ar-H); 13C NMR (CDCl3,
100 MHz): d 21.89, 27.89, 41.43, 42.49, 46.38, 51.83, 64.23, 65.90,
108.43, 114.44, 126.11, 127.91, 128.09, 129.43, 129.66, 130.09,
133.80, 137.54, 141.69, 143.24, and 144.70; Mass spectrum (EI,
70 eV): m/z, 524.14 (M+). Anal. Calcd for C28H29ClN2O2S2: C,
64.04, H, 5.57, N, 5.33. Found: C, 64.12, H, 5.50, N, 5.41.
4.7.5. (2R,3aR,4S,6aR,7aR)-cis-2-(p-Bromo)-phenyl-4-benzyl-5-
N-(p-methyl)-benzenesulfonyl perhydrothiazolo[30,40-2,3]-
pyrrolo[4,5-c]pyrrole, 10e
Colorless solid, 69% (0.393 g); ½a D29
ꢀ
¼ ꢁ13:8 (c 1, CHCl3); Mp:
4.7.1. (2S,3aR,4S,6aR,7aR)-cis-2-Phenyl-4-benzyl-5-N-
(p-methyl)-benzenesulfonyl perhydrothiazolo[30,40-2,3]-
pyrrolo[4,5-c]pyrrole, 10a
162–164 °C; IR (KBr): 1339 and 1166 cmꢁ1 1H NMR (CDCl3,
;
400 MHz): d 1.69–1.72 (m, 1H), 1.80–1.85 (m, 1H), 2.45 (s, 3H),
2.64–2.79 (m, 3H), 3.06–3.08 (m, 1H), 3.24–3.30 (m, 2H), 3.47–
3.49 (m, 1H), 3.66–3.71 (m, 1H), 3.75–3.78 (dd, 2H, J = 2.9,
9.8 Hz), 4.53 (s, 1H), 6.66–7.74 (m, 13H, Ar-H); 13C NMR (CDCl3,
100 MHz): d 21.69, 34.07, 39.23, 40.36, 41.48, 54.23, 67.71, 68.70,
72.73, 74.72, 120.55, 126.71, 127.74, 128.12, 128.62, 129.62,
130.81, 134.42, 137.81, 141.92, and 143.22; Mass spectrum (EI,
70 eV): m/z, 570.08 (M+). Anal. Calcd for C28H29BrN2O2S2: C,
59.04, H, 5.13, N, 4.92. Found: C, 59.12, H, 5.05, N, 5.00.
Brownish viscous liquid, 68% (0.333 g); ½a D29
¼ ꢁ10:6 (c 1,
ꢀ
CHCl3); IR (KBr): 1335 and 1165 cmꢁ1
;
1H NMR (CDCl3,
400 MHz): d 1.68–1.70 (m, 1H), 1.87–1.85 (m, 1H), 2.43 (s, 3H),
2.66–2.76 (m, 3H), 3.07–3.10 (m, 1H), 3.25–3.30 (m, 2H), 3.47–
3.49 (m, 1H), 3.69–3.72 (m, 1H), 3.74–3.78 (dd, 2H, J = 2.9,
9.8 Hz), 4.54 (s, 1H), 6.74–7.73 (m, 14H, Ar-H); 13C NMR (CDCl3,
100 MHz): d 21.89, 27.37, 41.77, 42.07, 46.14, 51.93, 64.81, 65.09,
108.68, 114.08, 126.02, 127.05, 128.67, 129.53, 129.08, 130.02,
133.19, 137.06, 141.25, 143.54, and 144.16; Mass spectrum (EI,
70 eV): m/z, 490.54 (M+). Anal. Calcd for C28H30N2O2S2: C, 68.54,
H, 6.16, N, 5.71. Found: C, 68.47, H, 6.08, N, 5.77.
4.7.6. (2S,3aR,4S,6aR,7aR)-cis-2-(p-Fluoro)phenyl-4-benzyl-5-N-
(p-methyl)-benzenesulfonyl perhydrothiazolo[30,40-2,3]-
pyrrolo[4,5-c]pyrrole, 10f
Brownish viscous liquid, 66% (0.335 g); ½a D29
ꢀ
¼ ꢁ15:6 (c 1,
4.7.2. (2S,3aR,4S,6aR,7aR)-cis-2-(p-Methyl)-phenyl-4-benzyl-5-
N-(p-methyl)-benzenesulfonyl perhydrothiazolo[30,40-2,3]-
pyrrolo[4,5-c]pyrrole, 10b
CHCl3); IR (KBr): 1338 and 1170 cmꢁ1 1H NMR (CDCl3,
;
400 MHz): d 1.68–1.72 (m, 1H), 1.79–1.85 (m, 1H), 2.46 (s, 3H),
2.63–2.78 (m, 3H), 3.07–3.09 (m, 1H), 3.23–3.32 (m, 2H), 3.47–
3.55 (m, 1H), 3.66–3.71 (m, 1H), 3.74–3.79 (dd, 2H, J = 2.9,
9.8 Hz), 4.55 (s, 1H), 6.64–7.68 (m, 13H, Ar-H); 13C NMR (CDCl3,
100 MHz): d 21.37, 27.16, 41.88, 42.54, 46.98, 51.87, 64.00, 65.21,
Brownish viscous liquid, 67% (0.338 g); ½a D29
ꢀ
¼ ꢁ14:8 (c 1,
CHCl3); IR (KBr): 1335 and 1170 cmꢁ1
;
1H NMR (CDCl3,
400 MHz): d 1.69–1.73 (m, 1H), 1.79–1.84 (m, 1H), 2.43 (s, 3H),