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M. Ikoma et al. / Tetrahedron 64 (2008) 2740e2749
0.9 Hz, 1H), 4.47 (dd, J¼9.2, 4.5 Hz, 1H), 4.46 (d, J¼14.7 Hz,
1H), 4.44 (br d, J¼9.2 Hz, 1H), 4.34 (d, J¼14.7 Hz, 1H), 3.97
(dt, J¼12.0, 5.1 Hz, 3H), 3.78 (s, 3H), 3.63 (dt, J¼12.0, 5.1 Hz,
1H), 3.40 (d, J¼11.1 Hz, 2H), 3.29 (d, J¼11.1 Hz, 2H), 3.14 (br
s, 1H), 2.34 (dd, J¼5.1, 5.1 Hz, 2H); 13C NMR (125 MHz,
CDCl3) d 170.9, 159.2, 138.3, 129.8, 129.5, 127.7, 126.3,
115.0, 114.1, 83.4, 82.9, 82.6, 69.1, 61.2, 57.0, 55.3, 46.0,
30.6; HRMS (ESI, positive) calcd for C20H24NO4 [(MþH)þ]
342.1705, found 342.1705.
7.5 Hz, 1H), 5.29 (d, J¼17.0 Hz, 1H), 4.49 (d, J¼15.0 Hz,
1H), 4.34 (d, J¼15.0 Hz, 1H), 4.15 (dd, J¼17.0, 4.0 Hz, 1H),
4.07 (d, J¼17.0 Hz, 2H), 4.06 (br s, 1H), 3.42 (d, J¼11.0 Hz,
1H), 3.41 (m, 1H), 3.31 (d, J¼11.0 Hz, 1H), 3.30 (m, 1H),
3.16 (s, 1H), 2.75 (m, 1H), 2.66 (m, 1H); 13C NMR (for the
(E)-isomer, 125 MHz, CDCl3) d 170.3, 159.1, 138.6, 131.0,
127.7, 114.9, 114.2, 84.8, 78.7, 73.2, 64.2, 59.8, 57.0, 55.2,
45.9, 35.3, 31.9; HRMS (ESI, positive) calcd for C21H25NO4
[(MþH)þ] 434.0967, found 434.0970.
4.2.20. Heterotricycle 29
By the same procedure for the synthesis of 26, the heterotri-
cycle 29 was synthesized from 24 in 81% yield as a colorless
4.2.23. 2-Acetoxyvinyl heterotricycle 32
By the same procedure for the synthesis of 30, the 2-acetoxy-
vinyl heterotricycle 32 (E/Z¼5:4) was synthesized from 21 in
88% yield accompanied by undesired 26 (10%) as a brown solid:
IR (film) 2935, 1757, 1684, 1513, 1247, 1213, 1088, 1035, 818,
solid: IR (film) 2928, 1699, 1249, 1163, 839, 736, 701 cmꢁ1
;
1H NMR (500 MHz, CDCl3) d 7.29 (br s, 1H), 7.13 (br s,
2H), 6.82 (br s, 2H), 5.91 (dd, J¼11.0, 17.0 Hz, 1H), 5.75 (br
s, 2H), 5.14 (br d, J¼17.0 Hz, 1H), 5.01 (br d, J¼11.0 Hz,
1H), 4.58 (br d, J¼5.0 Hz, 1H), 4.55e4.35 (m, 4H), 4.23 (br
d, J¼18.5 Hz, 1H), 3.77 (br s, 3H), 3.52 (br d, J¼18.5 Hz,
1H), 3.33 (d, J¼4.0 Hz, 1H), 3.30 (br s, 1H), 3.19 (d,
J¼4.0 Hz, 1H), 1.49 (s, 9H); 13C NMR (125 MHz, CDCl3)
d 171.7, 159.1, 154.2, 140.2, 129.6, 129.4, 128.0, 125.7,
114.1, 113.2, 84.8, 84.1, 80.7, 73.3, 58.0 (ꢂ2), 55.2 (ꢂ2),
45.7, 28.3; HRMS (ESI, positive) calcd for C24H31N2O5
[(MþH)þ] 427.2233, found 449.2228.
1
763 cmꢁ1; H NMR (300 MHz, CDCl3) d 7.33 (d, J¼12.2 Hz,
1.3H), 7.16 (d, J¼9.0 Hz, 2H), 7.13 (d, J¼9.0 Hz, 2H), 6.97 (d,
J¼7.0 Hz, 1H), 6.85 (d, J¼9.0 Hz, 2.6H), 6.83 (d, J¼9.0 Hz,
2H), 6.05 (dd, J¼10.8, 3.0 Hz, 2.6H), 5.96 (m, 1H), 5.57 (d,
J¼12.3 Hz, 1.3H), 5.27 (d, J¼7.0 Hz, 1H), 4.51e4.45 (m,
2.3H), 4.37e4.31 (m, 4.6H), 4.19e3.96 (m, 6.9H), 3.78 (s,
3.9H), 3.77 (s, 3H); 13C NMR (125 MHz, CDCl3) d 170.3,
170.2, 167.7, 166.5, 159.2, 159.2, 137.4, 133.1, 131.4, 131.0,
129.6, 129.5, 127.9, 127.6, 122.0, 121.9, 116.5, 115.6, 114.2,
114.1, 85.4, 82.9, 82.5, 78.6, 76.6, 73.4, 72.6, 64.4, 64.1, 60.5,
59.9, 58.6, 57.2, 55.3, 46.1, 46.0, 20.6, 20.5; HRMS (ESI, posi-
tive)calcdforC19H22NO4 [(MþH)þ]386.1604,found386.1602.
4.2.21. Styryl heterotricycle 30
To a stirred solution of the diene 21 (3.0 mg, 9.2 mmol)
in CH2Cl2 (2.5 mL) at rt were added styrene (0.0053 mL,
0.046 mmol) and the second-generation HoveydaeGrubbs
catalyst 25 (0.3 mg, 0.46 mmol).34 After 12 h, the mixture was
concentrated under reduced pressure. The residue was purified
by column chromatography on silica gel (0.5 g, hexane/
EtOAc¼7:3) to give the styryl heterotricycles 30 (E/Z¼6:5,
1.2 mg, 47%) and 26 (0.75 mg, 33%). The styryl heterotricycle
30 is a brown solid: IR (film) 2933, 1684, 1512, 1248, 1090,
753, 695 cmꢁ1; 1H NMR (500 MHz, CDCl3) d 7.31e7.15 (m,
5H), 7.16 (d, J¼9.0 Hz, 2H), 6.86 (d, J¼9.0 Hz, 2H), 6.59 (d,
J¼16.0 Hz, 1H), 6.28 (d, J¼16.0 Hz, 1H), 6.07 (dd, J¼10.3,
3.5 Hz, 1H), 6.02 (dd, J¼11.5, 1.5 Hz, 1H), 4.50 (d,
J¼14.5 Hz, 1H), 4.39 (d, J¼14.5 Hz, 1H), 4.37 (s, 1H), 4.15
(dd, J¼14.0, 3.0 Hz, 1H), 4.06 (t, J¼15.0 Hz, 2H), 3.53 (d,
J¼11.5 Hz, 1H), 3.40 (d, J¼11.5 Hz, 1H), 3.24 (s, 1H); 13C
NMR (125 MHz, CDCl3) d 170.5, 159.2, 136.4, 133.6, 131.2,
130.0, 129.8, 129.5, 128.4, 128.1, 127.7, 126.6, 122.0, 114.2,
85.0, 78.7, 73.3, 64.2, 60.2, 57.5, 55.3, 46.1; HRMS (ESI,
positive) calcd for C25H26NO4 [(MþH)þ] 404.1856, found
404.1868.
4.2.24. Aldehyde 33
To a stirred solution of the vinyl acetate 32 (78.4 mg,
0.20 mmol) in MeOH (2.0 mL) at ꢁ10 ꢀC was added AcCl
(0.0284 mL, 0.40 mmol). After 12 h, saturated aqueous
NaHCO3 (10 mL) was added and the mixture was extracted
with EtOAc (20 mL). The extract was washed with brine
(15 mL), dried over Na2SO4, and concentrated under reduced
pressure. The residue was purified by column chromatography
on silica gel (2 g, hexane/EtOAc¼6:4) to give the intermediary
dimethyl acetal (65.1 mg, 83%) as a colorless solid: IR (film)
2925, 1684, 1516, 1247, 1034, 819, 742 cmꢁ1 1H NMR
;
(300 MHz, CDCl3) d 7.14 (d, J¼8.7 Hz, 2H), 6.86 (d,
J¼8.7 Hz, 2H), 6.04 (dd, J¼10.7, 4.2 Hz, 1H), 5.96
(dd, J¼10.7, 3.5 Hz, 1H), 4.58 (q, J¼3.0 Hz, 1H), 4.49 (d,
J¼14.4 Hz, 1H), 4.32 (br d, J¼4.2 Hz, 1H), 4.29 (d,
J¼14.4 Hz, 1H), 4.32 (s, 1H), 4.29 (d, J¼14.4 Hz, 1H), 4.18
(dd, J¼17.4, 3.5 Hz, 1H), 4.06 (d, J¼17.4 Hz, 1H), 3.99 (br s,
1H), 3.80 (s, 3H), 3.43 (d, J¼11.4 Hz, 1H), 3.30 (d,
J¼11.4 Hz, 1H), 3.28 (s, 3H), 3.24 (s, 3H), 3.17 (s, 1H), 2.17
(dd, J¼14.1, 3.0 Hz, 1H), 1.95 (dd, J¼14.1, 3.0 Hz, 1H); 13C
NMR (125 MHz, CDCl3) d 170.6, 159.1, 131.0, 129.3, 128.0,
122.3, 114.1, 101.9, 83.3, 78.8, 72.8, 62.3, 58.8, 57.8, 55.3,
53.7, 52.3, 45.9, 41.4; HRMS (ESI, positive) calcd for
C21H28NO6 [(MþH)þ] 390.1917, found 390.1917.
4.2.22. 4-Bromo-1-butenyl heterotricycle 31
By the same procedure for the synthesis of 30, the 4-bromo-
1-butenyl heterotricycle 31 (E/Z¼2:1) was synthesized from 21
in 45% yield accompanied by undesired 26 (45%) as brown
solid: IR (film) 2934, 1683, 1513, 1248, 1213, 1085, 1020,
To a stirred solution of the intermediary dimethyl acetal
(65.1 mg, 0.17 mmol) thus obtained above in THF (5.0 mL)
at rt was added hydrochloric acid (1 M, 5.0 mL). After 5 h,
saturated aqueous NaHCO3 (10 mL) was added and the mix-
ture was extracted with EtOAc (20 mL). The extract was dried
1
810 cmꢁ1; H NMR (for the (E)-isomer, 300 MHz, CDCl3)
d 7.13 (d, J¼8.0 Hz, 2H), 6.85 (d, J¼8.0 Hz, 2H), 6.05 (dd,
J¼7.0, 5.5 Hz, 1H), 5.98 (d, J¼7.0 Hz, 1H), 5.69 (dt, J¼17.0,