I. Duttagupta et al. / Tetrahedron 68 (2012) 8347e8357
8355
(MþNa)þ calculated for C20H32N2O8Naþ¼451.2056, found
81.08, 77.36, 73.72, 73.15, 72.76, 71.93, 61.46, 61.29, 61.18, 50.41,
49.51, 48.23, 33.60, 32.95, 32.41, 28.12, 28.08, 28.05, 27.80, 26.46,
25.57, 25.26, 25.09, 24.49, 14.04, 13.94, 13.85; HRMS (ESI) (MþNa)þ
calculated for C22H38N2O8Naþ¼481.2526 found 481.2524. Anal.
Calcd for C22H38N2O8: C, 57.62; H, 8.35; N, 6.11. Found: C, 56.21; H,
8.31; N, 5.79.
451.2055.
4.2.11.2. 1,2-Di-tert-butoxycarbonyl-1,4,5,8,-tetrahydro-[1,2]-2H-
diazocine-3,3-dicarboxylic acid diethyl ester 15b. Yield (from 0.08 g,
0.16 mmol of 9b) 69% (0.052 g, 0.11 mmol). 1H NMR (500 MHz,
CDCl3)
d 5.51e5.67 (m, 1H), 5.38e5.46 (m, 1H), 4.60e4.70 (m, 1H),
4.25e4.34 (m, 1H), 4.10e4.25 (m, 3H), 3.66e3.89 (m, 1H),
2.52e2.68 (m, 2H), 2.36e2.41 (m, 1H), 2.16e2.25 (m, 1H), 1.41e1.51
4.2.12.3. 1,2-Di-iso-propoxycarbonyl-[1,2]diazonane-3,3-dicarbo-
xylic acid diethyl ester 16c. Yield (from 0.053 g, 0.12 mmol of 15c)
(m, 18H), 1.23e1.31 (m, 6H); 13C NMR (125 MHz, CDCl3)
d
168.44,
98% (0.052 g, 0.12 mmol). 1H NMR (500 MHz, CDCl3)
d 4.88e4.95
168.28,155.35, 153.41, 127.60, 81.58, 81.12, 72.49, 61.95, 61.69, 47.34,
31.50, 28.50, 28.40, 28.29, 28.06, 21.84, 14.24, 14.15, 14.09; HRMS
(ESI) (MþNa)þ calculated for C22H36N2O8Naþ¼479.2369, found
479.2369.
(m, 2H), 4.20e4.21 (m, 4H), 3.90e4.02 (m, 1H), 3.15 (br s, 1H),
1.86e2.44 (m, 3H), 1.43e1.63 (m, 7H), 1.12e1.26 (m, 18H); 13C NMR
(125 MHz, CDCl3)
d 167.31, 157.05, 154.02, 73.40, 70.95, 69.97,
69.73, 61.64, 61.20, 54.06, 53.60, 53.26, 32.10, 29.49, 28.64, 28.13,
27.50, 27.30, 25.84, 25.16, 21.86, 21.70, 21.54, 20.97, 20.81,
13.82, 13.78; HRMS (ESI) (MþNa)þ calculated for C21H36
N2O8Naþ¼467.2367, found 467.2368. Anal. Calcd for C21H36N2O8 C,
56.74; H, 8.16; N, 6.30. Found: C, 55.52; H, 8.12; N, 6.05.
4.2.11.3. 1,2-Di-iso-propoxycarbonyl-1,2,4,5,8,9-hexahydro-[1,2]
diazonine-3,3-dicarboxylic acid diethyl ester 15c. Yield (from
0.096 g, 0.2 mmol of 9c) 63% (0.055 g, 0.126 mmol). 1H NMR
(500 MHz, CDCl3)
d 5.56e5.65 (m, 1H), 5.49e5.56 (m, 0.76H),
5.37e5.46 (m, 0.24H), 4.94e5.07 (m, 1H), 4.84e4.96 (m, 1H),
4.19e4.29 (m, 2H), 4.05e4.18 (m, 2H), 3.98e4.01 (m, 0.78H),
3.74e3.81 (m, 0.22H), 2.99e3.04 (m, 1H), 2.35e2.69 (m, 4H),
2.00e2.20 (m, 1H), 1.84e1.96 (br m, 1H), 1.11e1.32 (m, 18H); 13C
4.2.12.4. 1,2-Di-tert-butoxycarbonyl-[1,2]diazonane-3,3-dicarbo-
xylic acid diethyl ester 16d. Yield (from 0.049 g, 0.10 mmol of 15d)
98% (0.048 g, 0.10 mmol). 1H NMR (500 MHz, CDCl3)
d 4.20e4.30
(m, 4H), 3.80e4.10 (br m, 1H), 3.05e3.25 (br m, 1H), 2.03e2.40 (m,
NMR (125 MHz, CDCl3)
d 168.52, 168.42, 156.91, 156.07, 154.57,
2H), 1.44e1.69 (m, 25H), 1.25e1.33(m, 7H); 13C NMR (125 MHz,
154.38, 129.67, 127.28, 72.98, 70.38, 70.11, 69.89, 62.11, 61.98, 61.82,
61.75, 47.51, 32.34, 31.40, 25.11, 24.83, 22.29, 22.17, 22.10, 22.07,
22.00, 21.81, 14.26, 14.17, 14.09, 14.04; HRMS (ESI) (MþNa)þ calcu-
lated for C21H34N2O8Naþ¼465.2213, found 465.2213.
CDCl3) d 169.06, 168.51, 168.10, 81.32, 73.70, 73.01, 61.67, 61.50,
61.38, 54.77, 54.07, 53.86, 30.50, 29.90, 29.80, 29.46, 29.05, 28.36,
28.36, 28.32, 28.09, 27.93, 27.49, 26.07, 23.89, 23.09, 21.84, 21.13,
20.94, 14.00; HRMS (ESI) (MþNa)þ calculated for C23H40
N2O8Naþ¼495.2682, found 495.2684. Anal. Calcd for C23H40N2O8:
C, 58.46; H, 8.53; N, 5.93. Found: C, 57.30; H, 8.57; N, 5.73.
4.2.11.4. 1,2-Di-tert-butoxycarbonyl-1,2,4,5,8,9-hexahydro-[1,2]
diazonine-3,3-dicarboxylic acid diethyl ester 15d. Yield (from
0.085 g, 0.17 mmol of 9d) 67% (0.056 g, 0.114 mmol). 1H NMR
4.2.13. 3,4-Di-iso-propoxycarbonyl-[3,4]-diaza-bicyclo[6.1.0]
nonane-dicarboxylic acid diethyl ester 17 To a solution of 15a
(24 mg, 0.056 mmol) in diethyl ether (1 ml) was added Pd(OAc)2
(1.3 mg, 10 mol %). The resulting mixture was allowed to stir along
with the dropwise addition of CH2N2 solution in ether. After the
completion of the reaction (TLC), ether was removed and the
compound was purified by silica gel column (10% EA in PE) to yield
the cyclopropane fused ring 17 (24 mg, 97%).
(500 MHz, CDCl3)
d 5.62e5.66 (m, 1H), 5.50e5.62 (m, 1H),
4.09e4.32 (m, 4H), 3.97e4.01 (m, 1H), 3.00 (br m, 1H), 2.59e2.67
(m, 3H), 2.45e2.41 (m, 1H), 2.10e2.16 (m, 1H), 1.87 (br m, 1H),
1.40e1.53 (m, 18H), 1.21e1.35 (m, 6H); 13C NMR (125 MHz, CDCl3)
d
168.74, 168.66, 156.34, 153.68, 129.71, 81.62, 81.16, 81.09, 72.61,
61.99, 61.87, 61.74, 61.68, 53.56, 32.54, 29.83, 28.52, 28.31, 28.09,
25.20, 25.00, 21.88, 14.34, 14.08, 12.26; HRMS (ESI) (MþNa)þ cal-
culated for C23H38N2O8Naþ¼493.2526, found 493.2526.
1H NMR (500 MHz, CDCl3)
d 4.88e4.97 (m, 2H), 4.50e4.65 (m,
1H), 4.11e4.29 (m, 4H), 2.57e2.63 (m, 2H), 2.30e2.50 (m, 1H),
2.00e2.20 (m, 1H), 1.18e1.31 (m, 18H), 1.00e1.15 (br s, 1H),
0.80e1.00 (m, 2H), 0.55e0.75 (m, 1H), ꢂ0.12 to ꢂ0.07 (m, 1H); 13C
4.2.12. Synthesis of 16 To a solution of 15a (40 mg, 0.093 mmol) in
methanol (4 ml) was added 10% Pd/C (6 mg) and the resulting
mixture was then stirred under hydrogen atmosphere (1 atm) for
4 h. The reaction was monitored by TLC and was filtered through
Celite. After purification by silica gel column chromatography (10%
EA in PE) gave the saturated ring.
NMR (125 MHz, CDCl3)
d 167.55, 167.49, 165.50, 156.66, 154.91,
153.78, 74.17, 73.49, 70.98, 70.31, 70.18, 69.80, 69.33, 62.43, 62.26,
62.14, 61.99, 61.88, 61.76, 48.37, 31.73, 31.50, 30.94, 29.82, 24.22,
23.71, 22.58, 22.48, 22.31, 22.19, 22.15, 22.07, 22.01, 21.95, 15.84,
15.28, 15.05, 14.99, 14.79, 14.53, 14.37, 14.26, 14.19, 14.08, 14.02,
13.97, 13.83, 11.52, 11.26, 10.63, 7.93; HRMS (ESI) (MþNa)þ calcu-
lated for C21H34N2O8Naþ¼465.2213, found 465.2214.
4.2.12.1. 1,2-Di-iso-propoxycarbonyl-[1,2]diazocane-3,3-dicarbo-
xylic acid diethyl ester 16a. Yield (from 15a) 99% (0.39 g,
0.092 mmol). 1H NMR (500 MHz, CDCl3)
d 4.91e4.96 (m, 2H),
4.17e4.29 (m, 4H), 3.95 (br s, 0.64H), 3.76 (br s, 0.36H), 3.10e3.35
(br m, 1H), 2.46 (m, 1H), 1.89e2.05 (m, 1H), 1.71 (br s, 5H), 1.45e1.47
4.2.14. Synthesis of 18 To a stirring solution of 11d (0.104 g,
0.29 mmol) in dry DMF (2 ml) was added NaH (8 mg, 0.35 mmol) at
0 ꢀC and was stirred for 15 min. Allyl bromide (42 mg, 0.35 mmol)
was added at the same temperature. The reaction mixture was then
allowed to stir for another 30 min followed by quenching with
0.1 ml of satd ammonium chloride solution. DMF was removed
under reduced pressure. The reaction mixture was then extracted
with diethyl ether (10 ml), washed with water and brine. Solvent
was removed in vacuo and silica gel column purification (10% EA in
PE) gave N-allylated product.
(m, 1H), 1.20e1.32 (m, 18H); 13C NMR (125 MHz, CDCl3)
d 168.36,
167.45, 157.24, 154.10, 71.17, 70.26, 70.13, 70.06, 61.94, 61.65, 53.52,
49.10, 32.40, 25.93, 25.46, 25.02, 22.15, 22.03, 21.86, 14.17, 14.09;
HRMS (ESI) (MþNa)þ calculated for C20H34N2O8Naþ¼453.2213,
found 453.2213.
4.2.12.2. 1,2-Di-tert-butoxycarbonyl-[1,2]diazocane-3,3-dicarbo-
xylic acid diethyl ester 16b. Yield (from 0.05 g, 0.11 mmol of 15b)
98% (0.049 g, 0.11 mmol). 1H NMR (500 MHz, CDCl3)
d 4.13e4.20 (br
m, 4H), 3.84 (br s, 0.63H), 3.57 (br s, 0.37H), 2.97e3.18 (m, 1H),
2.25e2.27 (br m, 1H), 1.85e1.91 (m, 1H), 1.60 (br s, 3H), 1.32e1.44
4.2.14.1. 2-(N’-Allyl-N,N0-di-tert-butoxycarbonyl-hydrazino)-hex-
5-enoic acid methyl ester 18a. Yield (from 0.104 g, 0.29 mmol of 11d)
(m, 19H), 1.12e1.18 (m, 8H); 13C NMR (125 MHz, CDCl3)
d
168.74,
84% (0.097 g, 0.24 mmol).1H NMR (500 MHz, CDCl3)
d
5.94e6.01 (m,
168.30, 167.96, 167.64, 157.17, 156.29, 155.35, 153.47, 152.99, 152.63,
1H), 5.76e5.81 (m, 1H), 4.97e5.24 (m, 4H), 4.60e4.72 (m, 0.21H),