Yamazaki et al.
JOCArticle
Selected HMBC correlations are between δ 4.42 (CHN) and δ
58.4 (C(CO2Et)2), 73.3 (CHOH) and between δ 7.44 (Ar) and δ
73.3 (CHOH). IR (neat) 3497, 3394, 2982, 1738, 1611, 1482,
1570, 1344, 1251, 1156, 1056 cm-1; MS (EI) m/z 393 (Mþ, 24),
320 (22), 292 (21), 246 (31), 202 (100%); HRMS Mþ 393.1786
(calcd for C20H27NO7 393.1788). Anal. Calcd for C20H27NO7:
C, 61.06; H, 6.92; N, 3.56. Found: C, 60.77; H, 6.75; N, 3.59.
6b: Rf = 0.8 (CH2Cl2/ether = 5:1); colorless crystals; mp
(d), 119.0 (d), 126.0 (d), 127.2 (s), 130.5 (s), 140.4 (s), 167.0 (s),
168.2 (s), 168.4 (s), 168.5 (s). Selected HMBC correlations are
between δ 4.45 (CHN) and δ 58.1 (C(CO2Et)2), 73.2 (CHOH)
and between δ 7.52 (Ar) and δ 73.2 (CHOH). IR (KBr) 3505,
3367, 2978, 1744, 1706, 1577, 1473, 1370, 1249, 1153 cm-1; MS
(EI) m/z 451 (Mþ, 18), 350 (70), 304 (66), 260 (100%); HRMS
Mþ 451.1846 (calcd for C22H29NO9 451.1842).
6f: Rf = 0.3 (CH2Cl2); yellow oil; 1H NMR (400 MHz,
CDCl3) δ (ppm) 1.11 (t, J = 7.1 Hz, 3H), 1.34 (t, J = 7.1 Hz,
3H), 1.49 (s, 9H), 4.09 (bs, 1H), 4.17 (q, J = 7.1 Hz, 2H),
4.29-4.35 (m, 2H), 4.39 (s, 1H), 4.76 (bs, 1H), 5.18 (bd, J = 11.2
Hz, 1H), 6.45 (d, J = 8.6 Hz, 1H), 7.13 (dd, J = 8.6, 2.4, 0.7 Hz,
1H), 7.55 (dd, J = 2.4, 1.1 Hz, 1H). Selected NOEs are between
δ 5.18 (CHOH) and δ 4.39 (CHN), 7.55 (Ar). 13C NMR (100.6
MHz, CDCl3) δ (ppm) 13.8 (q), 14.0 (q), 27.8 (q), 57.5 (d), 58.0
(s), 62.1 (t), 62.2 (t), 72.9 (d), 83.5 (s), 109.9 (s), 115.2 (d), 124.5
(s), 128.6 (d), 131.4 (d), 139.5 (s), 168.3 (s), 168.4 (s), 168.5 (s).
Selected HMBC correlations are between δ 4.39 (CHN) and δ
58.0 (C(CO2Et)2), 72.9 (CHOH) and between δ 7.55 (Ar) and δ
72.9 (CHOH). IR (neat) 3491, 3393, 2981, 1738, 1602, 1489,
1370, 1343, 1247, 1156, 1092, 1055 cm-1; MS (EI) m/z 473 (Mþ,
28), 471 (Mþ, 31), 372 (69), 370 (70), 326 (79), 324 (83), 282 (99),
280 (100%); HRMS Mþ 471.0883 (calcd for C20H2679BrNO7
471.0893), 473.0906 (calcd for C20H2681BrNO7 473.0872).
Typical Experimental Procedure (Table 1, entry 2). To a
solution of 1 (278 mg, 1.02 mmol) in 1,2-dichloroethane (1.9
mL) were added 2-amino-5-chlorobenzaldehyde (5b) (156 mg,
1.0 mmol) and Zn(OTf)2 (72 mg, 0.2 mmol). The mixture was
heated at 80 °C and stirred for 19 h. The reaction mixture
was cooled to 0 °C and quenched with water. The mixture was
diluted with dichloromethane, and then saturated aqueous
NaHCO3 was added. The organic phase was extracted with
dichloromethane, dried (Na2SO4), and evaporated in vacuo. The
residue was purified by column chromatography over silica gel
with dichloromethane as eluent to give 7b (318 mg, 90%).
7b: Rf = 0.2 (CH2Cl2); colorless crystals; mp 125-128 °C
(EtOAc); 1H NMR (400 MHz, CDCl3) δ (ppm) 1.03 (t, J = 7.1
Hz, 3H), 1.32 (t, J = 7.1 Hz, 3H), 3.99-4.11 (m, 1H), 4.12-4.19
(m, 1H), 4.27-4.39 (m, 2H), 4.58 (d, J = 3.3 Hz, 1H), 5.09 (bd,
J = 4.2 Hz, 1H), 5.50 (d, J = 1.1 Hz, 1H), 6.56 (d, J = 8.5 Hz,
1H), 7.13 (dd, J = 8.5, 2.4 Hz, 1H), 7.22 (d, J = 2.4 Hz, 1H).
Selected NOEs are between δ 5.09 (NH) and δ 4.58 (CHN), 6.56
(Ar) and between δ 5.50 (CHO) and δ 7.22 (Ar). 13C NMR
(100.6 MHz, CDCl3) δ (ppm) 13.6 (q), 13.9 (q), 56.1 (d), 57.5 (s),
62.3 (t), 63.5 (t), 79.0 (d), 116.1 (d), 121.5 (s), 123.7 (s), 128.2 (d),
130.8 (d), 138.9 (s), 164.0 (s), 166.5 (s), 170.1 (s). Selected HMBC
correlations are between δ 4.58 (CHN) and δ 138.9 (Ar), 79.0
(CHO), between δ 5.50 (CHO) and δ 56.1 (CHN), 121.5 (Ar),
57.5 (C(CO2Et)2), and between δ 7.22 (Ar) and δ 79.0 (CHO). IR
(KBr) 3402, 2991, 1792, 1726, 1488, 1305, 1254, 1234, 1144, 1047
cm-1; MS (EI) m/z 355 (Mþ, 5), 353 (Mþ, 14), 236 (100%);
HRMS Mþ 353.0670 (calcd for C16H1635ClNO6 353.0666), Mþ
355.0635 (calcd for C16H1637ClNO6 355.0637). Anal. Calcd for
C16H16ClNO6: C, 54.32; H, 4.56; N, 3.96. Found: C, 54.18; H,
4.56; N, 4.03.
1
118-119 °C (hexane-EtOAc); H NMR (400 MHz, CDCl3) δ
(ppm) 1.12 (t, J = 7.1 Hz, 3H), 1.34 (t, J = 7.1 Hz, 3H), 1.49 (s,
9H), 4.07-4.10 (broad, 2H), 4.16 (q, J = 7.1 Hz, 2H), 4.29-4.35
(m, 2H), 4.40 (s, 1H), 5.18 (bd, J = 8.1 Hz, 1H), 6.50 (d, J = 8.6
Hz, 1H), 7.01 (ddd, J = 8.6, 2.4, 0.7 Hz, 1H), 7.73 (dd, J = 2.4,
1.1 Hz, 1H). Selected NOEs are between δ 5.18 (CHOH) and δ
4.40 (CHN), 7.73 (Ar). 13C NMR (100.6 MHz, CDCl3) δ (ppm)
13.9 (q), 14.1 (q), 27.9 (q), 57.7 (d), 58.1 (s), 62.2 (t), 62.3 (t), 73.1
(d), 83.6 (s), 114.9 (d), 123.1 (s), 124.1 (s), 125.8 (d), 128.7 (d),
139.1 (s), 168.4 (s), 168.55 (s), 168.59 (s). Selected HMBC
correlations are between
δ 4.40 (CHN) and δ 58.1
(C(CO2Et)2), 73.1 (CHOH) and between δ 7.73 (Ar) and δ
73.1 (CHOH). IR (KBr) 3520, 3355, 2985, 1740, 1608, 1500,
1370, 1266, 1198, 1157 cm-1; MS (EI) m/z 429 (Mþ, 6.9), 427
(Mþ, 18), 326 (18), 280 (26), 236 (100%); HRMS Mþ 427.1399
(calcd for C20H2635ClNO7 427.1398), 429.1373 (calcd for
C20H2637ClNO7 429.1368). Anal. Calcd for C20H26ClNO7: C,
56.14; H, 6.12; N, 3.27. Found: C, 56.14; H, 6.10; N, 3.48.
6c: Rf = 0.3 (CH2Cl2) including a small amount of impurity;
1
pale yellow oil; H NMR (400 MHz, CDCl3) δ (ppm) 1.13 (t,
J = 7.1 Hz, 3H), 1.34 (t, J = 7.1 Hz, 3H), 1.49 (s, 9H), 4.08 (bs,
2H), 4.16 (q, J = 7.1 Hz, 2H), 4.29-4.34 (m, 2H), 4.41 (s, 1H),
5.18 (bs, 1H), 6.56 (d, J = 1.8 Hz, 1H), 6.71 (dd, J = 8.2, 2.0 Hz,
1H), 7.36 (dd, J = 8.2, 1.1 Hz, 1H). Selected NOEs are between
δ 5.18 (CHOH) and δ 4.41 (CHN), 7.36 (Ar). 13C NMR (100.6
MHz, CDCl3) δ (ppm) 13.9 (q), 14.0 (q), 27.8 (q), 57.6 (d), 58.2
(s), 62.15 (t), 62.24 (t), 73.1 (d), 83.6 (s), 113.1 (d), 118.2 (d), 121.1
(s), 127.2 (d), 134.3 (s), 141.5 (s), 168.3 (s), 168.5 (s), 168.6 (s).
Selected HMBC correlations are between δ 4.41 (CHN) and δ
58.2 (C(CO2Et)2), 73.1 (CHOH) and between δ 7.36 (Ar) and δ
73.1 (CHOH). IR (neat) 3500, 3390, 2981, 1755-1716, 1606,
1579, 1488, 1368, 1159, 1093, 1050 cm-1; MS (EI) m/z 429 (Mþ,
5.6), 427 (Mþ, 16), 326 (57), 280 (55), 236 (63), 57 (100%);
HRMS Mþ 427.1393 (calcd for C20H2635ClNO7 427.1398),
429.1361 (calcd for C20H2637ClNO7 429.1368).
6d: Rf = 0.2 (CH2Cl2/ether = 19:1); colorless viscous oil; 1H
NMR (400 MHz, CDCl3) δ (ppm) 1.08 (t, J = 7.1 Hz, 3H), 1.35
(t, J = 7.1 Hz, 3H), 1.50 (s, 9H), 3.85 (s, 3H), 4.13 (q, J = 7.1 Hz,
2H), 4.30-4.36 (m, 2H), 4.47 (s, 1H), 5.22 (s, 1H), 6.56 (d, J =
8.4 Hz, 1H), 7.76 (dd, J = 8.4, 1.6 Hz, 1H), 8.15 (dd, J = 1.8, 1.3
Hz, 1H). Selected NOEs are between δ 5.22 (CHOH) and δ 4.47
(CHN), 8.15 (Ar). 13C NMR (100.6 MHz, CDCl3) δ (ppm) 13.8
(q), 14.0 (q), 27.8 (q), 51.6 (q), 57.4 (d), 58.0 (s), 62.1 (t), 62.3 (t),
73.1 (d), 83.8 (s), 112.8 (d), 119.4 (s), 121.7 (s), 128.0 (d), 130.8
(d), 144.5 (s), 167.1 (s), 168.1 (s), 168.30 (s), 168.32 (s). Selected
HMBC correlations are between δ 4.47 (CHN) and δ 58.0
(C(CO2Et)2), 73.1 (CHOH) and between δ 8.15 (Ar) and δ
73.1 (CHOH). IR (neat) 3390, 2982, 1738, 1716, 1614, 1514,
1437, 1370, 1241, 1157, 1108, 1056 cm-1; MS (EI) m/z 451 (Mþ,
18), 350 (73), 304 (60), 260 (100%); HRMS Mþ 451.1841 (calcd
for C22H29NO9 451.1842).
7c: Rf = 0.2 (CH2Cl2); colorless crystals; mp 128-130 °C; 1H
NMR (400 MHz, CDCl3) δ (ppm) 1.06 (t, J = 7.1 Hz, 3H), 1.32
(t, J = 7.1 Hz, 3H), 4.00-4.08 (m, 1H), 4.10-4.18 (m, 1H),
4.28-4.40 (m, 2H), 4.58 (d, J = 2.6 Hz, 1H), 4.91 (bs, 1H), 5.53
(d, J = 2.0 Hz, 1H), 6.64 (d, J = 2.0 Hz, 1H), 6.77 (dd, J = 8.1,
2.0 Hz, 1H), 7.16 (d, J = 8.1 Hz, 1H). Selected NOEs are
between δ 4.91 (NH) and δ 4.58 (CHN), 6.64 (Ar) and between δ
5.53 (CHO) and δ 7.16 (Ar). 13C NMR (100.6 MHz, CDCl3) δ
(ppm) 13.7 (q), 14.0 (q), 56.0 (d), 57.7 (s), 62.4 (t), 63.5 (t), 79.1
(d), 114.7 (d), 118.8 (s), 119.5 (d), 129.8 (d), 136.7 (s), 141.3 (s),
164.0 (s), 166.5 (s), 169.9 (s). Selected HMBC correlations are
between δ 4.58 (CHN) and δ 141.3 (Ar), between δ 5.53 (CHO)
and δ 56.0 (CHN), 129.8 (Ar), 57.7 (C(CO2Et)2), and between δ
6e: Rf = 0.4 (CH2Cl2/ether = 19:1); pale yellow crystals; mp
116-118 °C; 1H NMR (400 MHz, CDCl3) δ (ppm) 1.10 (t, J =
7.1 Hz, 3H), 1.34 (t, J = 7.1 Hz, 3H), 1.50 (s, 9H), 3.87 (s, 3H),
4.13 (q, J = 7.1 Hz, 2H), 4.25 (bs, 2H), 4.32 (q, J = 7.1 Hz, 2H),
4.45 (s, 1H), 5.24 (bs, 1H), 7.25 (d, J = 1.6 Hz, 1H), 7.40 (dd, J =
8.1, 1.5 Hz, 1H), 7.52 (d-like, J = 8.1 Hz, 1H). Selected NOEs
are between δ 5.24 (CHOH) and δ 4.45 (CHN), 7.52 (Ar). 13
C
NMR (100.6 MHz, CDCl3) δ (ppm) 13.8 (q), 14.0 (q), 27.8 (q),
52.0 (q), 57.6 (d), 58.1 (s), 62.1 (t), 62.2 (t), 73.2 (d), 83.5 (s), 114.5
J. Org. Chem. Vol. 75, No. 4, 2010 1193