The Journal of Organic Chemistry
NOTE
5
1
7
8
1
.3, 2.6 Hz, 1H, H-5b), 2.10 (br s, 1H), 2.91 (ddd, J = 13.4, 5.3, 2.4 Hz,
H, H-6a), 2.98 (ddd, J = 13.4, 11.9, 3.1 Hz, 1H, H-6b), 3.37 (dq, J = 9.0,
(CH
2
), 61.5 (CH
2
), 65.3 (CH
2
), 65.8 (CH
2
), 75.2 (CH, C-4), 118.5
(CH ), 131.8 (CH), 168.5 (C), 169.1 (C), 171.2 (C); IR (neat) 3321,
2979, 2935, 1738, 1649, 1446, 1368, 1273, 1211, 1182, 1103,
1083 cm ; MS (EI) m/z 357 (M ); HRMS m/z M 357.1786 (calcd
for C H NO 357.1788). Anal. Calcd for C H NO : C, 57.13; H,
2
.0 Hz, 1H), 3.58 (dq, J = 9.0, 7.0 Hz, 1H, OCHHCH
3
), 4.12À4.29 (m,
, H-4, H-2); C NMR (100.6 MHz, CDCl ) δ (ppm)
3.9 (CH ), 14.05 (CH ), 14.08 (CH ), 15.4 (CH ), 26.0 (CH ), 40.2
13
À1
+
+
H, CO
2
CH
2
CH
3
3
3
3
3
3
2
17 27
7
17 27
7
(
6
(
1
3
C
CH , C-6), 58.8 (C, C-3), 59.3 (CH, C-2), 61.1 (CH ), 61.2 (CH ),
1.6 (CH ), 65.3 (CH ), 75.3 (CH, C-4), 168.6 (C), 169.2 (C), 171.5
2 2
7.61; N, 3.92. Found: C, 56.77; H, 7.75; N, 3.87.
Data for trans-3d: R = 0.5 (CH Cl :ether = 1:1); colorless oil; for
2
2
2
f
2
2
1
C); IR (neat) 3324. 2979, 2934, 1738, 1466, 1446, 1369, 1269, 1211,
major isomer, H NMR (400 MHz, CDCl ) δ (ppm) 1.13 (t, J = 7.1 Hz,
3
À1
+
+
103, 1080, 1032 cm ; MS (EI) m/z 345 (M ); HRMS m/z M
45.1790 (calcd for 345.1788). Anal. Calcd for
3H), 1.28 (t, J = 7.1 Hz, 3H), 1.29 (J = 7.1 Hz, 3H), 1.72 (dddd, J = 14.3,
C
16
H
27NO
7
3.1, 3.1, 3.1 Hz, 1H, H-5a), 2.00 (dddd, J = 14.3, 12.0, 5.2, 2.6 Hz, 1H,
H-5b), 2.07 (br s, 1H), 2.46 (t, J = 2.5 Hz, 3H), 2.91 (ddd, J = 13.1, 5.2,
2.3 Hz, 1H, H-6a), 2.98 (ddd, J = 13.1, 13.1, 3.2 Hz, 1H, H-6b), 3.38 (dq,
16
H
27NO
7
: C, 55.64; H, 7.88; N, 4.06. Found: C, 55.38; H, 7.95;
N, 4.25.
1
Data for cis-3a: R = 0.3 (CH Cl :ether = 1:1); colorless oil; H NMR
J = 9.0, 7.1 Hz, 1H), 3.58 (dq, J = 9.0, 7.1 Hz, 1H, OCHHCH ), 4.14 (dd,
f
2
2
3
(
400 MHz, CDCl
3
) δ (ppm) 1.15 (t, J = 7.0 Hz, 3H), 1.258 (t, J = 7.1 Hz,
J = 3.0, 3.0 Hz, 1H, H-4), 4.15À4.29 (m, 5H, CO CH CH , H-2), 4.72
2
2
3
1
3
3
1
2
H), 1.264 (t, J = 7.1 Hz, 3H), 1.31 (J = 7.1 Hz, 3H), 1.75 (dddd, J = 13.0,
0.8, 10.8, 4.6 Hz, 1H), 1.84 (dddd, J = 13.0, 3.8, 3.8, 3.8 Hz, 1H, H-5b),
.11 (br s, 1H), 2.71 (ddd, J = 12.8, 10.8, 3.7 Hz, 1H, H-6a), 3.23 (ddd, J
(d, J = 2.5 Hz, 2H); C NMR (100.6 MHz, CDCl ) δ (ppm) 13.9
3
(CH ), 14.1 (CH ), 15.4 (CH ), 26.0 (CH ), 40.2 (CH , C-6), 52.6
3
3
3
2
2
(CH ), 58.9 (C, C-3), 59.1 (CH, C-2), 61.3 (CH ), 61.7 (CH ), 65.4
2
2
2
=
12.8, 4.1, 4.1 Hz, 1H), 3.46 (dq, J = 9.3, 7.0 Hz, 1H), 3.66 (dq, J = 9.3,
(CH ), 75.1 (CH), 75.2 (CH, C-4), 168.4 (C), 169.0 (C), 170.7 (C); IR
2
7
4
.0 Hz, 1H), 3.76 (s, 1H, H-2), 3.85 (dd, J = 10.8, 4.0 Hz, 1H, H-4),
(neat) 3270, 2979, 2936, 2129, 1743, 1445, 1369, 1269,1209, 1104,
1081 cm ; MS (EI) m/z 355 (M ); HRMS m/z M 355.1624 (calcd
13
À1
+
+
.14À4.32 (m, 6H); C NMR (100.6 MHz, CDCl ) δ (ppm) 14.00
3
(CH
3
), 14.01 (CH
), 61.3 (CH
), 80.8 (CH, C-4), 167.5 (C), 169.6 (C), 170.1 (C); IR (neat)
364, 2979, 1739, 1466, 1445, 1369, 1301, 1260, 1104, 1063,
3
), 14.1 (CH
3
), 15.5 (CH
3
), 28.0 (CH
2
), 42.7 (CH
2
,
for C H NO 355.1635).
1
7
25
7
C-6), 61.2 (CH
2
2
), 61.7 (CH
2
), 63.0 (CH), 63.2 (C, C-3),
Data for trans-3e: R = 0.5 (CH Cl :ether = 1:1); colorless oil; for
f 2 2
1
6
3
1
5.7 (CH
2
major isomer, H NMR (400 MHz, CDCl ) δ (ppm) 1.14 (t, J = 7.1 Hz,
3
3H), 1.27 (t, J = 7.1 Hz, 3H), 1.28 (J = 7.1 Hz, 3H), 1.74 (dddd, J = 14.3,
À1
+
+
037 cm ; MS (EI) m/z 345 (M ); HRMS m/z M 345.1790 (calcd
345.1788).
3.0, 3.0, 3.0 Hz, 1H, H-5a), 1.96 (dddd, J = 14.3, 12.1, 5.1, 2.5 Hz, 1H,
H-5b), 2.08 (br s, 1H), 2.92 (ddd, J = 13.0, 5.1, 2.2 Hz, 1H, H-6a), 3.00
(ddd, J = 13.0, 13.0, 3.1 Hz, 1H, H-6b), 3.38 (dq, J = 9.0, 7.0 Hz, 1H),
for C16H27NO
7
Experimental Procedure (Table 1, Entry 6). To a solution of
(244 mg, 1.0 mmol) in dichloromethane (2 mL) were added 2a (147
1
3.58 (dq, J = 9.0, 7.0 Hz, 1H, OCHHCH
CO CH CH
, H-4), 4.30 (s, 1H, H-2), 4.41À4.57 (m, 2H);
NMR (100.6 MHz, CDCl ) δ (ppm) 13.8 (CH ), 14.0 (CH ), 15.40
(CH ), 26.1 (CH ), 40.1 (CH , C-6), 58.6 (CH, C-2), 59.2 (C, C-3),
60.9 (CH , q, JCF = 37 Hz), 61.4 (CH ), 61.8 (CH ), 65.4 (CH ), 75.3
(CH, C-4), 122.9 (C, q, JCF = 277 Hz), 168.3 (C), 168.7 (C), 170.4 (C);
3
), 4.14À4.29 (m, 5H,
13
mg, 1.0 mmol) and TiCl
mixture was stirred at room temperature for 18 h. The reaction mixture
was quenched with water. The mixture was diluted with dichloro-
methane, and then saturated aqueous NaHCO
phase was extracted with dichloromethane, dried (Na
evaporated in vacuo. The residue was purified by column chromatog-
raphy over silica gel with dichloromethaneÀether as the eluent to give
trans-3a (296 mg, 86%).
4
(0.330 mL, 567 mg, 3.0 mmol) at 0 °C. The
2
2
3
C
3
3
3
3
2
2
3
was added. The organic
SO ), and
2
2
2
2
2
4
1
9
F NMR (376 MHz, CDCl
3
) δ (ppm) À73.88 (t, JFH = 8.4 Hz); IR
(neat) 3322, 2979, 1741, 1446, 1414, 1369, 1281, 1164, 1105,
À1
+
+
1082 cm ; MS (EI) m/z 399 (M ); HRMS m/z M 399.1502 (calcd
for C16 NO 399.1505). Anal. Calcd for C16 NO : C, 48.12;
H, 6.06; N, 3.51. Found: C, 48.40; H, 6.17; N, 3.56.
Data for cis-3f: R = 0.3 (CH Cl :ether = 1:1); pale yellow crystals;
) δ (ppm) 1.16 (t, J = 7.1
Data for trans-3b: R
f
= 0.6 (CH
2
Cl
2
:ether = 1:1); colorless oil; for
H
24
F
3
7
H
24
F
3
7
1
major isomer, H NMR (400 MHz, CDCl ) δ (ppm) 1.13 (t, J = 7.0 Hz,
3
3
3
H), 1.26 (d, J = 6.2 Hz, 3H), 1.27 (d, J = 6.0 Hz, 3H), 1.28 (t, J = 7.1 Hz,
H), 1.29 (J = 7.1 Hz, 3H), 1.71 (dddd, J = 14.3, 3.2, 3.2, 3.2 Hz, 1H,
f
2
2
1
mp 48À50 °C; H NMR (400 MHz, CDCl
3
H-5a), 2.00 (dddd, J = 14.3, 11.8, 5.1, 2.6 Hz, 1H, H-5b), 2.15 (br s, 1H),
.91 (ddd, J = 13.1, 5.1, 2.4 Hz, 1H, H-6a), 2.98 (ddd, J = 13.1, 13.1, 3.2
Hz, 1H, H-6b), 3.37 (dq, J = 9.1, 7.0 Hz, 1H), 3.58 (dq, J = 9.1, 7.0 Hz,
H, OCHHCH CH CH
), 4.13 (s, 1H, H-2), 4.14À4.30 (m, 5H, CO
H-4), 5.03 (septet, J = 6.2 Hz, 1H); C NMR (100.6 MHz, CDCl ) δ
Hz, 3H), 1.27 (t, J = 7.1 Hz, 3H), 1.31 (J = 7.1 Hz, 3H), 1.46 (s, 9H), 1.76
(dddd, J = 12.8, 11.7, 11.7, 4.7 Hz, 1H), 1.86 (dddd, J = 12.8, 3.5, 3.5, 3.5
Hz, 1H, H-5b), 2.10 (br s, 1H), 2.67 (ddd, J = 12.5, 12.5, 3.5 Hz, 1H,
H-6a), 3.20 (ddd, J = 12.6, 4.6, 2.7 Hz, 1H), 3.43 (dq, J = 9.5, 7.1 Hz,
1H), 3.56 (s, 1H, H-2), 3.67 (dq, J = 9.5, 7.1 Hz, 1H), 3.77 (dd, J = 11.4,
2
1
3
2
2
3
,
13
3
1
3
(
2
(
1
1
ppm) 13.9 (CH
6.0 (CH ), 40.1 (CH
CH ), 61.5 (CH ), 65.3 (CH
69.1 (C), 171.0 (C); IR (neat) 3321, 2979, 1734, 1466, 1446, 1374,
3
), 14.1 (CH
, C-6), 58.9 (C, C-3), 59.3 (CH, C-2), 61.1
), 68.6 (CH), 75.3 (CH, C-4), 168.6 (C),
3
), 15.4 (CH
3
), 21.6 (CH
3
), 21.7 (CH
3
),
4.3 Hz, 1H, H-4), 4.17À4.35 (m, 4H); C NMR (100.6 MHz, CDCl
δ (ppm) 14.0 (CH ), 14.1 (CH ), 15.4 (CH ), 27.9 (CH ), 28.0 (CH
43.2 (CH , C-6), 60.9 (CH ), 61.3 (CH ), 63.4 (C, C-3), 63.9 (CH),
65.7 (CH
IR (KBr) 3363, 2979, 1732, 1474, 1366, 1255, 1166, 1104, 1041 cm
MS (EI) m/z 373 (M ), 374 ((M + H) ); HRMS m/z M 373.2103
3
)
),
2
2
3
3
3
3
2
2
2
2
2
2
2
2
), 81.8 (C), 81.9 (CH, C-4), 167.4 (C), 168.9 (C), 169.5 (C);
À1
+
À1
267, 1212, 1106, 1081 cm ; MS (EI) m/z 359 (M , 15), 316 (64), 272
;
+
+
+
+
(85), 200 (92), 154 (100); HRMS m/z M 359.1943 (calcd for
C H NO 359.1944).
(calcd for C18
H
31NO
7
373.2101). Anal. Calcd for C18
H
31NO
7
: C,
1
7
29
7
Data for trans-3c: R
f
= 0.5 (CH
pale yellow oil; H NMR (400 MHz, CDCl
Hz, 3H), 1.27 (t, J = 7.1 Hz, 3H), 1.28 (J = 7.1 Hz, 3H), 1.72 (dddd, J =
2
Cl
2
:ether = 1:1); for major isomer,
57.89; H, 8.37; N, 3.75. Found: C, 57.93; H, 8.52; N, 3.61.
1
1
) δ (ppm) 1.13 (t, J = 7.1
Data for trans-3g: R
NMR (400 MHz, CDCl
f
= 0.3 (ether:MeOH = 4:1); colorless oil; H
) δ (ppm) 1.27 (t, J = 7.1 Hz, 3H), 1.285 (t, J =
3
3
1
1
2
1
1
5
1
4.3, 3.1, 3.1, 3.1 Hz, 1H, H-5a), 2.01 (dddd, J = 14.3, 11.9, 5.2, 2.6 Hz,
H, H-5b), 2.13 (br s, 1H), 2.91 (ddd, J = 13.1, 5.2, 2.2 Hz, 1H, H-6a),
.98 (ddd, J = 13.1, 13.1, 3.2 Hz, 1H, H-6b), 3.38 (dq, J = 9.0, 7.1 Hz,
7.1 Hz, 3H), 1.286 (t, J = 7.1 Hz, 3H), 1.74 (dddd, J = 14.1, 4.1, 4.1, 4.1
Hz, 1H, H-5a), 1.97 (dddd, J = 14.1, 10.9, 4.8, 3.0 Hz, 1H, H-5b), 2.30
(br s, 2H), 2.88 (ddd, J = 13.5, 4.3, 4.3 Hz, 1H, H-6a), 3.00 (ddd, J = 13.5,
10.8, 3.5 Hz, 1H, H-6b), 3.43À3.48 (m, 1H), 3.63À3.76 (m, 3H,
3
H), 3.59 (dq, J = 9.0, 7.1 Hz, 1H, OCHHCH ), 4.14 (dd, J = 2.6, 2.6 Hz,
1
3
H, H-4), 4.15À4.29 (m, 4H), 4.21 (s, 1H, H-2), 4.58À4.68 (m, 2H),
OCHHCH
NMR (100.6 MHz, CDCl
(CH ), 26.1 (CH ), 39.9 (CH
61.4 (CH ), 61.68 (CH ), 61.71 (CH
C-4), 168.5 (C), 169.2 (C), 171.1 (C); IR (neat) 3368, 2981, 2938,
2
OH), 4.13À4.30 (m, 8H, CO
) δ (ppm) 13.8 (CH
, C-6), 58.9 (C, C-3), 59.4 (CH, C-2),
 2), 71.0 (CH ), 75.3 (CH,
2
CH
2
CH
3
, H-2, H-4);
C
.23 (dddd, J = 10.4, 1.3, 1.3, 1.3 Hz, 1H), 5.35 (dddd, J = 17.2, 1.5, 1.5,
3
), 13.96 (CH
3
), 14.02
3
1
3
.5 Hz, 1H), 5.93 (dddd, J = 17.2, 10.4, 5.8, 5.8 Hz, 1H); C NMR
100.6 MHz, CDCl ) δ (ppm) 13.8 (CH ), 14.0 (CH ), 15.4 (CH ),
5.9 (CH ), 40.1 (CH , C-6), 58.7 (C, C-3), 59.2 (CH, C-2), 61.1
3
2
2
(
2
3
3
3
3
2
2
2
2
2
2
6
435
dx.doi.org/10.1021/jo201011n |J. Org. Chem. 2011, 76, 6432–6437