The Journal of Organic Chemistry
Page 24 of 30
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1.5 Hz, 1H), 6.17 (dd, J = 16.3, 3.8 Hz, 1H), 5.63 (d, J = 12.8 Hz, 1H), 5.16 (dd, J = 12.9, 10.8 Hz,
1H), 5.00 (d, J = 10.8 Hz, 1H), 4.80 (ddd, J = 9.0, 3.9, 2.2 Hz, 1H), 4.58 – 4.43 (m, 2H), 4.08 (dd, J =
10.6, 8.9 Hz, 1H), 3.89 (d, J = 10.5 Hz, 1H), 1.52 (t, J = 7.2 Hz, 3H). 13C{1H}NMR (125 MHz,
Chloroform-d) δ 175.0, 173.9, 170.0, 167.2, 144.4, 140.3, 138.6, 136.5, 133.8, 132.1, 128.9, 128.5,
128.5, 128.4, 128.1, 127.8, 127.7, 127.5, 127.0, 126.6, 126.5, 125.5, 125.2, 124.8, 110.1, 82.5, 67.6,
64.5, 62.8, 51.5, 51.2, 50.6, 44.5, 14.3. IR (film) νmax 3427, 2926, 2361, 2101, 1712, 1498, 1262, 751
cm-1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C40H35N4O5S 683.2323; Found 683.2300.
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Ethyl (3aS,4R,6S,7R,8R,8aS,8bR)-8-methyl-1,3-dioxo-2,6-diphenyl-7-(1H-pyrazole-1-carbonyl)-
4-((E)-styryl)octahydropyrrolo[3,4-a]pyrrolizine-8a(6H)-carboxylate (9ma): White solid, 80 mg,
65% yield. Rf = 0.45 (20% EtOAc in hexanes). MP: 84−87 °C. dr = 80:20 [α]D23 = +96.30 (CH2Cl2, c
= 0.49 for 92% ee). HPLC(Chiralpak ID , n-hexane/ iso-propanol = 70/30, 1.0 mL/min, 254 nm): tR =
9.54 min (minor), 12.84 min (major).1H NMR (500 MHz, Chloroform-d) δ 7.67 (d, J = 2.8 Hz, 1H),
7.62 (d, J = 1.4 Hz, 1H), 7.41 (dd, J = 8.5, 7.1 Hz, 2H), 7.33 (dd, J = 8.0, 2.1 Hz, 3H), 7.16 – 7.10 (m,
3H), 7.07 – 7.00 (m, 5H), 6.90 – 6.86 (m, 2H), 6.82 (dd, J = 16.3, 2.2 Hz, 1H), 6.21 (dd, J = 2.9, 1.5
Hz, 1H), 6.02 (dd, J = 16.2, 3.9 Hz, 1H), 4.70 (s, 1H), 4.67 (ddd, J = 8.8, 3.9, 2.3 Hz, 1H), 4.34 – 4.23
(m, 2H), 4.20 (dd, J = 12.7, 10.9 Hz, 1H), 3.97 – 3.90 (m, 2H), 3.66 (d, J = 10.5 Hz, 1H), 1.32 – 1.28
(m, 6H). 13C{1H}NMR (125 MHz, Chloroform-d) δ 175.5, 175.0, 170.5, 168.3, 144.0, 140.7, 136.5,
133.3, 132.3, 129.1, 128.5, 128.5, 128.3, 127.9, 127.7, 127.6, 127.4, 126.7, 126.5, 125.3, 109.8, 82.7,
67.2, 65.1, 62.3, 52.8, 50.7, 50.7, 38.3, 14.2, 13.9. IR (film) νmax 3430, 2360, 2101, 1710, 1646, 1495,
1188, 750 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C37H35N4O5 615.2602; Found 615.2615.
Ethyl
(3aS,4R,6S,7R,8S,8aS,8bR)-4-((E)-4-bromostyryl)-1,3-dioxo-2,6,8-triphenyl-7-(1H-
pyrazole-1-carbonyl)octahydropyrrolo[3,4-a]pyrrolizine-8a(6H)-carboxylate (9ab): White solid,
95 mg, 63% yield. Rf = 0.44 (20% EtOAc in hexanes). MP: 115−118 °C. dr = 88:12 [α]D24 = +80.81
(CH2Cl2, c = 0.82 for 98% ee). HPLC (Chiralpak ID , n-hexane/ iso-propanol = 70/30, 1.0 mL/min,
254 nm): tR = 11.43 min (minor), 28.47 min (major). 1H NMR (500 MHz, Chloroform-d) δ 7.69 (d, J
= 1.4 Hz, 1H), 7.64 (d, J = 2.8 Hz, 1H), 7.37 (d, J = 7.4 Hz, 2H), 7.32 (dd, J = 8.3, 7.0 Hz, 2H), 7.29 –
7.23 (m, 5H), 7.23 – 7.18 (m, 3H), 7.07 (dd, J = 5.1, 2.0 Hz, 3H), 6.99 – 6.95 (m, 2H), 6.94 – 6.90 (m,
2H), 6.79 (dd, J = 16.4, 2.2 Hz, 1H), 6.25 (dd, J = 2.9, 1.5 Hz, 1H), 6.06 (dd, J = 16.3, 3.9 Hz, 1H),
5.40 (d, J = 12.9 Hz, 1H), 5.19 – 5.10 (m, 1H), 4.88 (d, J = 10.7 Hz, 1H), 4.55 (ddd, J = 9.1, 3.9, 2.2
Hz, 1H), 4.47 – 4.36 (m, 2H), 3.92 (dd, J = 10.5, 8.9 Hz, 1H), 3.67 (d, J = 10.5 Hz, 1H), 1.40 (t, J =
7.1 Hz, 3H). 13C{1H}NMR (125 MHz, Chloroform-d) δ 175.0, 173.7, 170.3, 167.5, 144.3, 140.6,
135.4, 135.1, 132.6, 131.6, 128.9, 128.9, 128.5, 128.4, 128.1, 128.0, 127.9, 127.8, 127.7, 127.5, 126.6,
125.7, 121.6, 110.0, 82.9, 66.9, 64.5, 62.7, 50.8, 50.7, 49.3, 47.8, 14.3. IR (film) νmax 3441, 3058,
2926, 2855, 2122, 1712, 1495, 1264, 743, 622 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd for
C42H36BrN4O5 755.184; Found 755.1887.
Ethyl
(3aS,4R,6S,7R,8S,8aS,8bR)-4-((E)-4-methoxystyryl)-1,3-dioxo-2,6,8-triphenyl-7-(1H-
pyrazole-1-carbonyl)octahydropyrrolo[3,4-a]pyrrolizine-8a(6H)-carboxylate (9ac): White solid,
85 mg, 60% yield. Rf = 0.42 (20% EtOAc in hexanes). MP: 249−252 °C. dr = 87:13 [α]D25 = +107.47
(CH2Cl2, c = 1.15 for 92% ee). HPLC (Chiralpak IA , n-hexane/ iso-propanol = 60/40, 1.0 mL/min,
254 nm): tR = 8.47 min (minor), 21.76 min (major). 1H NMR (500 MHz, Chloroform-d) δ 7.69 (d, J =
1.5 Hz, 1H), 7.64 (d, J = 2.9 Hz, 1H), 7.40 – 7.35 (m, 2H), 7.32 (t, J = 7.7 Hz, 2H), 7.27 – 7.16 (m,
6H), 7.07 (dd, J = 5.0, 1.9 Hz, 3H), 7.03 – 7.00 (m, 2H), 6.99 (dd, J = 6.6, 3.0 Hz, 2H), 6.80 (dd, J =
16.2, 2.2 Hz, 1H), 6.72 – 6.68 (m, 2H), 6.24 (dd, J = 2.9, 1.5 Hz, 1H), 5.93 (dd, J = 16.3, 4.0 Hz, 1H),
5.40 (d, J = 13.0 Hz, 1H), 5.13 (dd, J = 13.0, 10.7 Hz, 1H), 4.94 (d, J = 10.7 Hz, 1H), 4.56 (ddd, J =
9.0, 4.0, 2.2 Hz, 1H), 4.46 – 4.35 (m, 2H), 3.91 (dd, J = 10.6, 9.0 Hz, 1H), 3.70 (s, 3H), 3.65 (d, J =
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