Y. Li et al. / Tetrahedron 67 (2011) 4002e4008
4007
(dd, J¼6.7, 3.0 Hz, 1H, H-4), 3.23 (dd, J¼11.4, 8.9 Hz, 1H, H-3),
3.16e3.07 (m, 1H, H-30), 3.00 (dd, J¼9.2, 2.7 Hz, 1H, H-3b), 2.92 (dt,
J¼14.7, 4.4 Hz, 2H, H-6a, 70), 2.76e2.64 (m,1H, H-2), 1.23 (d, J¼7.1 Hz,
5.4.6. (3S,3bS,4R,5S,6R,6aR)-5,6-Di-O-isopropylidene-4-benzyloxy-
octahydrocyclopenta[c]pyrazol[1,2-a]-3-phenylpyrazolidin-1-one
25
3dd-S. [
d
a
]
þ73.6 (c 3.81, CHCl3); 1H NMR (400 MHz, CDCl3)
D
3H, eCH3); 13C NMR (101 MHz, CDCl3)
d
176.28, 138.54, 138.12,
7.81e7.02 (m, 10H), 4.76 (d, J¼12.3 Hz, 1H, eCH2OPh), 4.68 (d,
138.07, 128.73, 128.71, 128.57, 128.24, 128.11, 128.01, 127.95, 127.90,
127.85, 127.76, 90.89, 86.58, 84.52, 77.55, 77.23, 76.91, 72.90, 72.61,
72.50, 70.34, 54.67, 48.29, 46.61, 37.25,15.27; HRMS (ES) m/z calcd for
C31H34N2O4 [MþH]þ: 499.2597, found: 499.2594.
J¼5.4 Hz,1H, H-5), 4.54 (d, J¼12.3 Hz,1H, eCH2OPh), 4.21 (d, J¼9.9 Hz,
1H, 3), 4.17 (d, J¼5.4 Hz,1H, H-4), 3.92 (d, J¼6.9 Hz,1H, H-6), 3.87e3.76
(m, 1H, H-7), 3.56 (dd, J¼11.4, 3.6 Hz, 1H, H-70), 3.48 (dt, J¼16.1, 5.8 Hz,
1H, H-6a), 3.27 (d, J¼7.4 Hz,1H, H-3b), 2.99 (dd, J¼16.4, 8.6 Hz,1H, H-2),
2.86 (dd, J¼16.3,10.6 Hz,1H, H-20),1.37 (s, 3H, eCH3),1.15 (s, 3H, eCH3);
13C NMR (101 MHz, CDCl3)
d 166.33, 139.98, 138.01, 128.88, 128.55,
5.4.2. (2R,3bS,4R,5S,6S,6aR)-4,5,6-Tris(benzyloxy)octahydrocyclopenta
25
128.17, 127.83, 127.52, 127.13, 110.97, 85.97, 83.10, 81.49, 77.55, 77.23,
76.91, 76.64, 71.94, 68.53, 48.92, 44.08, 39.48, 26.98, 24.61; HRMS (ES)
m/z calcd for C25H28N2O4 [MþH]þ: 421.2127, found: 421.2124.
[c]pyrazol[1,2-a]-2-methylpyrazolidin-1-one 3ab-R. [
a
]
þ17.4 (c
D
1.15, CHCl3); 1H NMR (400 MHz, CDCl3)
d
7.75e6.97 (m, 15H),
4.76e4.52 (m, 6H, 3ꢂeCH2OPh), 4.17e4.09 (m, 1H, H-4), 3.90 (ddd,
J¼11.1, 9.9, 5.5 Hz, 3H, H-5, 6, 7), 3.77 (t, J¼8.7 Hz,1H, H-3), 3.05 (ddd,
J¼17.4, 10.5, 4.3 Hz, 2H, H-3b, 70), 2.99e2.87 (m, 2H, H-30, 6a), 2.40
(dd, J¼11.9, 9.1 Hz, 1H, H-2), 1.20 (d, J¼7.1 Hz, 3H, eCH3); 13C NMR
5.4.7. (3R,3bS,4R,5S,6R,6aR)-5,6-Di-O-isopropylidene-4-benzyloxy-
octahydrocyclopenta[c]pyrazol[1,2-a]-3-phenylpyrazolidin-1-one
25
(101 MHz, CDCl3)
d
167.85, 138.46, 138.07, 137.89, 128.72, 128.56,
3dd-R. [
d
a
]
D
ꢁ40.0 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3)
128.23, 128.11, 127.99, 127.85, 127.75, 90.47, 85.98, 84.73, 77.55, 77.23,
76.91, 72.87, 72.72, 72.54, 72.40, 60.00, 48.14, 44.32, 41.32, 14.43;
HRMS (ES) m/z calcd for C31H34N2O4 [MþH]þ: 499.2597, found:
499.2594.
7.49e7.08 (m, 10H), 4.63 (tt, J¼7.0, 5.7 Hz, 3H, H-5, 6, eCH2OPh),
4.52 (t, J¼9.1 Hz, 1H, H-3), 4.41 (d, J¼11.6 Hz, 1H, eCH2OPh), 3.89
(dd, J¼11.3, 4.8 Hz, 1H, H-7), 3.79 (dd, J¼6.5, 4.3 Hz, 1H, H-4), 3.60
(t, J¼7.0 Hz, 1H, H-3b), 3.35 (t, J¼10.7 Hz, 1H, H-7), 3.27 (ddd,
J¼12.3, 11.1, 7.2 Hz, 1H, H-6a), 2.74 (dd, J¼9.1, 1.8 Hz, 2H, H-2, 20),
1.57 (s, 3H, eCH3), 1.33 (s, 3H, eCH3); 13C NMR (101 MHz, CDCl3)
5.4.3. (3R/S,3bS,4R,5S,6S,6aR)-4,5,6-Tris(benzyloxy)octahy-
drocyclopenta[c]pyrazol[1,2-a]-3-methylpyrazolidin-1-one
3ac-RS.
d 167.13, 139.58, 137.34, 128.89, 128.69, 128.52, 128.30, 128.20,
Mixture of 3ac-R and 3ac-S. 1H NMR (400 MHz, CDCl3)
d
7.52e6.95 (m,
127.45, 113.47, 86.75, 81.31, 77.55, 77.23, 76.99, 76.91, 71.65, 69.34,
59.80, 46.95, 42.75, 39.40, 26.95, 25.10; HRMS (ES) m/z calcd for
C25H28N2O4 [MþH]þ: 421.2127, found: 421.2126.
30H), 4.87e4.52 (m, 12H), 4.13 (t, J¼7.3 Hz, 1H), 4.08 (t, J¼7.4 Hz, 1H),
4.00 (dd, J¼10.6, 7.7 Hz, 1H), 3.94 (t, J¼7.3 Hz, 1H), 3.90 (dd, J¼7.0,
3.9 Hz, 1H), 3.88e3.84 (m, 1H), 3.81 (t, J¼6.4 Hz, 1H), 3.65e3.50 (m,
3H), 3.24e3.13 (m, 2H), 3.05 (dd, J¼9.6, 3.8 Hz,1H), 3.00e2.86 (m, 2H),
2.66 (dd, J¼16.5, 8.0 Hz, 1H), 2.52 (dd, J¼16.7, 7.9 Hz, 1H), 2.40 (dd,
J¼16.5, 9.3 Hz,1H), 2.28 (dd, J¼16.7, 9.6 Hz, 1H), 1.25 (d, J¼6.4 Hz, 3H),
5.4.8. (3S,3bS,4R,5S,6R,6aR)-5,6-Di-O-isopropylidene-4-benzyloxy-
octahydrocyclopenta[c]pyrazol[1,2-a]-3-phenylpyrazolidin-1-one
25
3ed-S. [
d
a
]
ꢁ8.2 (c 1.47, CHCl3); 1H NMR (400 MHz, CDCl3)
D
1.21 (d, J¼6.5 Hz, 3H); 13C NMR (101 MHz, CDCl3)
d 168.98, 138.32,
7.62e7.05 (m,10H), 4.72 (dd, J¼15.0, 7.1 Hz, 2H, H-3, eCH2OPh), 4.63
138.20, 137.98, 137.81, 137.60, 128.76, 128.71, 128.60, 128.56, 128.28,
128.13, 128.02, 127.96, 127.86, 90.42, 89.18, 87.21, 86.43, 84.84, 77.55,
77.23, 76.91, 72.88, 72.83, 72.63, 72.40, 72.33, 72.26, 71.42, 63.89, 59.64,
51.83, 47.87, 47.58, 45.36, 41.06, 40.93, 20.41, 17.95; (R/S¼1:1).
(dd, J¼6.5, 3.4 Hz,1H, H-4), 4.47 (d, J¼12.1 Hz, 1H, eCH2OPh), 4.44 (d,
J¼6.7 Hz,1H, H-5), 3.95 (dd, J¼6.5, 3.3 Hz,1H, H-3b), 3.66 (dd, J¼11.8,
5.3 Hz, 1H, H-7), 3.54e3.41 (m, 1H, H-70), 3.38 (d, J¼6.9 Hz, 1H, H-6),
3.36e3.30 (m, 1H, H-6a), 3.13 (dd, J¼16.6, 8.7 Hz, 1H, H-2), 2.94 (dd,
J¼16.7, 8.7 Hz,1H, H-20),1.37(s,3H, eCH3),1.24(s, 3H, eCH3); 13CNMR
5.4.4. (3S,3bS,4R,5S,6S,6aR)-4,5,6-Tris(benzyloxy)octahydrocyclopenta
(101 MHz, CDCl3)
d 167.49, 137.74, 129.09, 128.63, 128.05, 127.99,
25
[c]pyrazol[1,2-a]-3-phenylpyrazolidin-1-one 3ad-S. [
a
]
þ28.6 (c
D
127.85, 112.37, 85.39, 83.08, 78.73, 77.55, 77.23, 76.91, 72.22, 67.82,
61.10, 50.06, 41.94, 39.81, 27.12, 24.85; HRMS (ES) m/z calcd for
C25H28N2O4 [MþH]þ: 421.2127, found: 421.2124.
1.12, CHCl3); 1H NMR (400 MHz, CDCl3)
d
7.60e6.81 (m, 20H), 4.77
(d, J¼11.6 Hz, 1H, eCH2OPh), 4.67 (d, J¼11.6 Hz, 1H, eCH2OPh),
4.64 (d, J¼11.7 Hz, 1H, eCH2OPh), 4.58e4.52 (m, 3H, H-3,
eCH2OPh), 4.50 (d, J¼11.6 Hz, 1H, eCH2OPh), 4.01 (t, J¼7.0 Hz, 1H,
H-5), 3.87 (t, J¼7.2 Hz, 1H, H-4), 3.78 (dd, J¼6.2, 5.0 Hz, 1H, H-6),
3.63 (dd, J¼8.9, 7.1 Hz, 1H, H-3b), 3.49e3.37 (m, 2H, H-7, 70), 2.94
(dt, J¼13.5, 4.6 Hz, 1H, H-6a), 2.82 (dd, J¼16.8, 9.1 Hz, 1H, H-2),
2.69 (dd, J¼16.8, 8.5 Hz, 1H, H-2); 13C NMR (101 MHz, CDCl3)
5.4.9. (3R,3bS,4R,5S,6R,6aR)-5,6-Di-O-isopropylidene-4-benzyloxy-
octahydro2c5yclopenta[c]pyrazol[1,2-a]-3-phenylpyrazolidin-1-one
3ed-R. [
a
]
þ115.3 (c 2.36, CHCl3); 1H NMR (400 MHz, CDCl3)
D
d
7.57e7.21 (m, 10H), 4.76 (d, J¼12.3 Hz, 1H, eCH2OPh), 4.69 (dd,
J¼5.4, 1.2 Hz, 1H, H-4), 4.54 (d, J¼12.3 Hz, 1H, eCH2OPh), 4.24e4.16
(m, 2H, H-3, 5), 3.92 (dd, J¼6.9, 1.3 Hz, 1H, H-3b), 3.81 (dd, J¼11.3,
9.1 Hz, 1H, H-7), 3.56 (dd, J¼11.4, 3.6 Hz, 1H, H-70), 3.49 (ddd, J¼16.1,
7.3, 3.9 Hz, 1H, H-6a), 3.27 (d, J¼7.4 Hz, 1H, H-6), 2.99 (dd, J¼16.4,
8.6 Hz,1H, H-2), 2.87 (dd, J¼16.4,10.5 Hz,1H, H-20),1.38 (s, 3H, eCH3),
d
165.07, 137.89, 137.46, 137.33, 129.35, 129.35, 128.85, 128.69,
128.69, 128.49, 128.39, 128.39, 128.24, 128.15, 128.00, 127.75, 88.11,
86.11, 86.06, 77.55, 77.23, 76.91, 72.90, 72.42, 71.96, 66.43, 47.59,
46.13, 46.10, 39.25; HRMS (ES) m/z calcd for C36H36N2O4 [MþH]þ:
561.2753, found: 561.2747.
1.16 (s, 3H, eCH3); 13C NMR (101 MHz, CDCl3)
d 166.73,140.16,138.09,
128.94, 128.61, 128.22, 127.89, 127.58, 127.18, 111.05, 86.08, 83.25,
81.60, 77.55, 77.23, 76.91, 76.69, 72.04, 68.48, 48.98, 44.06, 39.58,
27.05, 24.68; HRMS (ES) m/z calcd for C25H28N2O4 [MþH]þ: 421.2127,
found: 421.2126.
5.4.5. (3R,3bS,4R,5S,6S,6aR)-4,5,6-Tris(benzyloxy)octahydrocyclopenta
25
[c]pyrazol[1,2-a]-3-phenylpyrazolidin-1-one 3ad-R. [
a
]
ꢁ65.0 (c
D
0.80, CHCl3); 1H NMR (400 MHz, CDCl3)
d
7.46 (dd, J¼7.8, 1.5 Hz, 2H),
7.38e7.14 (m,17H), 6.96 (dd, J¼6.6, 3.0 Hz, 2H), 4.59 (ddd, J¼29.9, 21.8,
11.7 Hz, 4H, 2ꢂeCH2OPh), 4.15 (dd, J¼11.0, 8.4 Hz,1H, H-3), 4.08e3.93
(m,5H,H-4,5,6, eCH2OPh), 3.67 (dd, J¼5.6,2.5 Hz,1H, H-7), 3.19e3.07
(m, 3H, H-3b, 6a, 70), 2.96(dd, J¼16.4, 8.4 Hz,1H, H-2), 2.85 (dd, J¼16.3,
5.5. Preparation of compound (3bS,4R,5S,6S,6aR)-4,5,6-tris(hydr
oxy)octahydrocyclopenta[c]pyrazol[1,2-a]pyrazolidin-1-one 4aa
11.1 Hz, 1H, H-20); 13C NMR (101 MHz, CDCl3)
d 165.55, 138.25, 138.07,
137.91, 129.06, 128.76, 128.57, 128.48, 128.16, 127.97, 127.92, 127.70,
127.46, 90.99, 86.49, 84.80, 77.55, 77.23, 76.91, 72.77, 72.59, 72.34,
69.43, 53.62, 48.65, 44.50; HRMS (ES) m/z calcd for C36H36N2O4
[MþH]þ: 561.2753, found: 561.2740.
A suspension of 3aa (0.2 mmol, 97 mg) and Pd/C (10 mg) in MeOH
(2 mL) was stirred at rt under 0.4 MPa H2 atmosphere for 2 h. The re-
action mixture was filtered and concentrated to give the crude 4aa
(42 mg). Then the crude product was subjected to chromatography on