Xu et al.
JOCArticle
Allylic Alcohol 16. [R]2D3 -9.3 (c 2.02, MeOH); IR (KBr) 3476,
3372, 2975, 1731, 1505 cm-1; 1H NMR (300 MHz, CD3OD) two
existing rotamers, the main rotamer is shown, δ 8.06 (d, J = 6.9
Hz, 1H), 7.43 (s, 1H), 7.20-7.25 (m, 3H), 6.29 (d, J = 15.6 Hz,
1H), 4.47 (dd, J = 5.4, 9.6Hz, 1H), 3.68 (s, 3H), 3.37 (dd, J = 5.4,
15.0 Hz, 1H), 3.06 (dd, J = 9.6, 15.0 Hz, 1H), 1.65 (s, 9H), 1.44
(s, 6H), 1.36 (s, 9H); 13C NMR (75 MHz, CD3OD) δ 174.6,
158.0, 150.9, 142.5, 137.8, 133.3, 128.6, 126.4, 125.7, 125.4,
122.3, 117.8, 115.4, 84.9, 80.7, 71.7, 55.5, 52.7, 31.1, 29.7, 28.7,
28.4, 28.1; HRMS (ESI) m/z calcd for C27H38N2O7Na (M þ
Na)þ 525.2571, found 525.2576.
(d, J = 8.4 Hz, 2H), 7.64 (d, J = 8.0 Hz, 1H), 7.41 (s, 1H), 7.24
(d, J = 8.4 Hz, 2H), 6.91 (t, J = 8.0 Hz, 1H), 5.42 (dd, J = 4.4,
11.6 Hz, 1H), 4.11 (dd, J = 4.4, 15.2 Hz, 1H), 3.77 (s, 3H), 3.21
(dd, J = 11.6, 15.2 Hz, 1H), 2.32 (s, 3H), 1.26 (s, 18H); 13C NMR
(100 MHz, CDCl3) δ 170.5, 151.5, 145.1, 135.4, 134.7, 131.0,
130.1, 127.3, 126.9, 125.5, 118.1, 113.4, 85.2, 83.0, 58.5, 52.3,
27.6, 25.3, 21.5; HRMS (ESI) m/z calcd for C29H35IN2O8SNa
(M þ Na)þ 721.1051, found 721.1050.
trans-(5S,7R)-1N-Tosyl-6N-Boc-clavicipitic Acid Methyl Ester
21a. [R]2D3 -135 (c 2.00, CHCl3); IR (KBr) 2976, 2926, 1747,
1694, 1599 cm-1 1H NMR (400 MHz, CDCl3) showed the
;
One-Pot Preparation of trans-(5S,7R)-1N,6N-Di-Boc-clavici-
pitic Acid Methyl Ester 17a and cis-(5S,7S)-1N,6N-Di-Boc-
clavicipitic Acid Methyl Ester 17b. A suspension of 14 (198
mg, 0.307 mmol), 2-methyl-3-buten-2-ol (264 mg, 3.07 mmol),
Pd(OAc)2 (7.0 mg, 0.031 mmol), and Ag2CO3 (50.7 mg, 0.184
mmol) in benzene (2.0 mL) was heated at 90 °C for 1.5 h, and
then CH3CN (4.0 mL) was added followed by the addition of
Mg(ClO4)2 (82.2 mg, 0.368 mmol). The resultant reaction mix-
ture was stirred at 90 °C for an additional 3 h and cooled to room
temperature. The insoluble material was filtrated and washed
with EtOAc. The filtrate was evaporated to dryness and sub-
jected to FCC (PE-EtOAc, 10:1), affording the desired trans-
17a (112.3 mg, 75%), [R]D23 -150 (c 1.00, CHCl3), and cis-17b
(23.0 mg, 15%), [R]2D3 103 (c 1.00, CHCl3).
presence of two rotamers in a ratio of 1/2, δ 7.87 (d, J = 8.0 Hz,
1H, minor), 7.85 (d, J = 7.6 Hz, 1H, major), 7.75 (d, J = 8.8 Hz,
2H, both), 7.41 (s, 1H, both), 7.20-7.23 (m, 3H, both), 6.99
(d, J = 7.6 Hz, 1H, major), 6.94 (d, J = 6.8 Hz, 1H, minor), 6.36
(d, J = 7.2 Hz, 1H, major), 6.09 (br s, 1H, minor), 5.21 (br s, 1H,
minor), 5.12 (d, J = 6.8 Hz, 1H, major), 4.35 (br s, 1H, minor),
4.30 (dd, J = 2.8, 12.4 Hz, 1H, major), 3.72 (s, 3H, major), 3.71
(s, 3H, minor), 3.38-3.58 (m, 2H, both), 2.32 (s, 3H, major),
2.31 (s, 3H, minor), 1.85 (s, 3H, both), 1.74 (s, 3H, minor), 1.71
(s, 3H, major), 1.38 (s, 9H, major), 1.30 (s, 9H, minor); 13C
NMR (100 MHz, CDCl3) major rotamer shown, δ 171.2, 153.4,
144.8, 140.0, 138.0, 135.9, 135.1, 129.8, 126.8, 124.5, 124.2,
123.5, 123.2, 121.9, 118.4, 111.6, 80.9, 57.0, 55.6, 51.9, 28.2,
28.0, 25.5, 21.4, 18.7; HRMS (ESI) m/z calcd for C29H34N2O6S-
Na (M þ Na)þ 561.2030, found 561.2034.
(2S)-2-(Di-tert-butoxycarbonylamino)-3-(4-nitro-1N-tosyl-in-
dol-3-yl)propionic Acid Methyl Ester 19. To a solution of 11
(1.51 g, 3.26 mmol) in THF (25 mL) was added NaH (163 mg,
4.08 mmol, 60% oil dispersion) at -15 °C, and the mixture was
stirred for 5 min. Then TsCl (652 mg, 3.42 mmol) was added, and
the reaction mixture was stirred at room temperature for
30 min. Saturated NH4Cl, was added to the reaction followed
by extraction with EtOAc. The combined organic phases were
washed with brine and dried over Na2SO4. Purification by FCC
(PE-EtOAc, 4:1) afforded 19 (1.89 g, 94%) as white foam:
[R]2D3 -146 (c 2.00, CHCl3); IR (KBr) 2981, 1790, 1749, 1699,
1529 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 8.4 Hz,
1H), 7.93 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.58 (s,
1H), 7.33 (t, J = 8.4 Hz, 1H), 7.25 (d, J = 8.4 Hz, 2H), 5.21 (dd,
J = 4.8, 11.2 Hz, 1H), 3.76 (dd, J = 4.8, 14.8 Hz, 1H), 3.73
(s, 3H), 3.37 (dd, J = 11.2, 14.8 Hz, 1H), 2.32 (s, 3H), 1.24 (s,
9H); 13C NMR (100 MHz, CDCl3) δ 170.4, 151.6, 145.7, 143.3,
136.9, 134.3, 130.2, 130.1, 126.9, 123.6, 122.9, 120.4, 118.8,
116.3, 82.9, 57.9, 52.2, 27.9, 27.5, 21.4; HRMS (ESI) m/z calcd
for C29H35N3O10SNa (M þ Na)þ 640.1935, found 640.1927.
(2S)-2-(Di-tert-butoxycarbonylamino)-3-(4-iodo-1N-tosyl-indol-
3-yl)propionic Acid Methyl Ester 20. A solution of (2S)-2-(di-
tert-butoxycarbonylamino)-3-(4-amino-1N-tosyl-indol-3-yl)-
propionic acid methyl ester (1.78 g, 3.03 mmol), prepared from
19 following the same procedure as that of 13, was dissolved in
acetonitrile (12 mL) and cooled to 10 °C, and then p-toluene
sulfonic acid monohydrate (1.73 g, 9.09 mmol) was added to the
resultant solution. After 5 min, a solution of NaNO2 (469 mg,
6.80 mmol) and KI (1.29 g, 7.77 mmol) in water (2.5 mL) was
added dropwise, and the mixture was stirred at 10 °C for a
further 10 min, then warmed to room temperature, and stirred
for further 2 h. The reaction mixture was diluted with water and
extracted with EtOAc. The combined organic phases were
washed with satd NaHSO3, satd NaHCO3, and brine sequen-
tially and dried over Na2SO4. The solvent was removed under
reduced pressure, and the residue was dissolved in acetonitrile
(15 mL), followed by addition of Boc2O (331 mg, 1.52 mmol)
and DMAP (17 mg, 0.14 mmol). The resultant reaction mix-
ture was stirred at room temperature overnight. The solvent
was removed under reduced pressure. Purification by FCC
(PE-EtOAc, 5:1) afforded 20 (1.41 g, 66%) as white foam:
[R]2D3 -72 (c 1.00, CHCl3); IR (KBr) 2982, 1744, 1709 cm-1; 1H
NMR (400 MHz, CDCl3) δ 7.90 (d, J = 8.0 Hz, 1H), 7.72
cis-(5S,7S)-1N-Tosyl-6N-Boc-clavicipitic Acid Methyl Ester
21b. [R]2D3 þ63 (c 2.00, CHCl3); IR (KBr) 2975, 2929, 1756, 1736,
1692, 1599 cm-1 1H NMR (400 MHz, CDCl3) showed the
;
presence of two rotamers in a ratio of 1/1, δ7.74-7.83 (m, 3Hꢀ 2),
7.36 (d, J = 7.2 Hz, 1H ꢀ 2), 7.16-7.23 (m, 3H ꢀ 2), 7.05
(d, J = 7.2 Hz, 1H), 6.93 (d, J = 7.2 Hz, 1H), 6.36 (d, J = 7.6 Hz,
1H), 5.95 (d, J = 8.0 Hz, 1H), 5.32 (d, J = 8.0 Hz, 1H), 5.28
(d, J = 7.6 Hz, 1H), 5.15 (dd, J = 6.8, 12.0 Hz, 1H), 4.70
(dd, J = 5.2, 12.4 Hz, 1H), 3.72 (s, 3H), 3.69 (s, 3H), 3.47-3.54
(m, 1H ꢀ 2), 3.34 (dd, J = 7.2, 16.4 Hz, 1H), 3.24 (dd, J = 5.2,
16.0 Hz, 1H), 2.33 (s, 3H), 2.32 (s, 3H), 1.84 (s, 3H), 1.83 (s, 3H),
1.68 (s, 3H ꢀ 2), 1.32 (s, 9H), 1.21 (s, 9H); 13C NMR (100 MHz,
CDCl3) both rotamers shown, δ 172.8, 172.5, 155.4, 154.7,
144.9, 144.8, 139.9, 139.3, 138.2, 137.6, 135.6, 135.4, 135.3,
135.2, 129.85, 129.80, 128.7, 128.5, 126.8, 126.7, 124.9, 124.4,
124.0, 122.6, 122.5, 122.0, 121.3, 120.8, 118.55, 118.49, 112.2,
80.6, 80.4, 59.8, 57.5, 57.0, 55.7, 52.1, 51.9, 28.1, 28.0, 27.1, 26.7,
25.5, 25.4, 21.4, 18.8, 18.6; HRMS (ESI) m/z calcd for
C29H34N2O6SNa (M þ Na)þ 561.2030, found 561.2037.
trans-(5S,7R)-1N,6N-Di-Boc-clavicipitic Acid 24a. To a stir-
ring solution of 17a (102 mg, 0.21 mmol) in 2.8 mL of THF/H2O
(3:1) was added LiOH H2O (26.5 mg, 0.63 mmol). Then the
3
reaction was stirred at room temperature for 24 h until the
starting material was consumed. An additional 2.0 mL of H2O
was added, and the pH was adjusted to 6-7 by adding 5% HCl.
The reaction mixture was extracted with EtOAc, and the
combined organic layers were washed with brine and dried over
Na2SO4. The solvent was removed under reduced pressure to
give crude 24a as white amorphous powder: 1H NMR (400
MHz, DMSO-d6) showed the presence of two rotamers in a ratio
of 3/1, δ 8.29 (s, CO2H), 7.96 (d, J = 8.4 Hz, 1H, major), 7.93 (d,
J = 8.4 Hz, 1H, minor), 7.54 (s, 1H, major), 7.51 (s, 1H, minor),
7.22 (t, J = 8.4 Hz, 1H, major), 7.21 (t, J = 8.4 Hz, 1H, minor),
6.93 (d, J = 8.4 Hz, 1H, major), 6.91 (d, J = 8.4 Hz, 1H, minor),
6.29 (d, J = 7.6 Hz, 1H, major), 6.08 (br s, 1H, minor), 5.37 (br s,
1H, minor), 5.26 (d, J = 7.2 Hz, 1H, major), 4.46 (br s, 1H,
minor), 4.36 (dd, J = 2.8, 12.0 Hz, 1H, major), 3.25-3.45 (m,
2H, both), 1.81 (s, 3H, both), 1.72 (s, 3H, minor), 1.69 (s, 3H,
major), 1.59 (s, 9H, both), 1.32 (s, 9H, major), 1.25 (s, 9H,
minor); 13C NMR (100 MHz, CDCl3), major rotamer shown, δ
172.0, 153.2, 148.8, 137.5, 137.4, 135.8, 126.6, 124.1, 123.4,
121.2, 116.8, 112.8, 83.5, 80.0, 79.2, 56.5, 55.3, 27.8, 27.7, 25.4,
7634 J. Org. Chem. Vol. 75, No. 22, 2010