Catalytic Palladium-Mediated Bisdiene Carbocyclizations
J. Am. Chem. Soc., Vol. 119, No. 25, 1997 5811
2.00 (dd, 1 H, J ) 11.0, 11.0 Hz), 1.82-1.73 (m, 2 H), 1.34 (dddd, 1
H, J ) 12.5, 12.5, 12.5, 4.4 Hz), 1.14-1.06 (m, 1 H); 13C NMR (50
MHz) δ 143.3 (s), 136.4 (d), 135.6 (d), 133.8 (d), 133.6 (d), 133.0 (s),
129.5 (d), 127.6 (d), 116.7 (t), 50.9 (t), 46.3 (t), 44.6 (d), 39.5 (d),
37.4 (t), 29.6 (t), 21.4 (q); IR (ATR) 1651 (m, CdC), 1640 (m), 1341
(s, SO2), 1162 (s, SO2); Combustion analysis (C19H25NO2S ) 68.84%
C, 7.60% H) found 69.00% C, 7.42% H.
SO2); Combustion analysis (C21H29NO2S ) 70.15% C, 8.13% H) found
70.49% C, 8.27% H.
Cyclization of Bisdiene 24a. To a stirred solution of 24a (250.0
mg, 0.70 mmol) in THF (5 mL) was added Pd(OAc)2 (12.2 mg, 0.05
mmol), Ph3P (26-39 mg, 0.10-0.15 mmol), and Et3N (0.35 mL, 2.5
mmol). The resulting mixture was heated to reflux (20 h) to afford,
after chromatography on silica (95:5 Hex:EtOAc), piperidine 25a (215.0
mg, 86%): 1H NMR (500 MHz) δ 6.10 (dd, 1 H, J ) 15.1, 10.4 Hz),
5.97 (dd, 1 H, J ) 15.1, 10.3 Hz), 5.71 (dt, 1 H, J ) 15.1, 6.4 Hz),
5.58-5.70 (m, 1 H), 5.17 (dd, 1 H, J ) 15.1, 9.0 Hz), 4.98-4.93 (m,
2 H), 3.80-3.76 (m, 1 H), 3.68-3.63 (m, 1 H), 2.42 (s, 3 H), 2.31-
2.06 (m, 5 H), 1.94 (dd, 1 H, J ) 12.1, 12.1 Hz), 1.74-1.61 (m, 2 H),
1.23 (dddd, 1 H, J ) 12.3, 12.3, 12.3, 4.2 Hz), 1.06-1.00 (m, 1 H),
1.00 (t, 3 H, J ) 7.4 Hz); 13C NMR (50 MHz) δ 143.3 (s), 136.0 (d),
135.8 (d), 133.5 (d), 133.1 (s), 130.5 (d), 129.5 (d), 128.6 (d), 127.6
(d), 116.6 (t), 51.2 (t), 46.4 (t), 44.6 (d), 39.6 (d), 37.5 (t), 29.7 (t),
21.4 (q); IR (ATR) 1658 (m, CdC), 1640 (m, CdC), 1342 (s, SO2),
1163 (s, SO2); Combustion analysis (C21H29NO2S ) 70.15% C, 8.13%
H) found 70.49% C, 8.37% H.
Preparation of 7,7-(Diethylcarboxyl)pentadeca-1,3,9,11-tetraene
(24b). To a mixture of (E)-(3,5-hexadienyl)propanedioic acid diethyl
ester40 (950 mg, 4.0 mmol) and NaH (200 mg, 8 mmol) in THF (75
mL) was added 2,4-octadienyl chloride (600 mg, 4.5 mmol). The
resulting mixture was stirred overnight (12 h), then quenched by the
careful addition of water (50 mL), and concentrated in vacuo. The
residue was extracted with EtOAc (100 mL), and the organic extract
was washed with brine (2 × 50 mL), then dried (Na2SO4), filtered,
and concentrated. Chromatography on silica (95:5 Hex:EtOAc) af-
forded bisdiene 24a (1.160 g, 87%): 1H NMR (360 MHz) δ 6.21-
6.30 (m, 1 H), 5.91-6.06 (m, 3 H), 5.52-5.67 (m, 2 H), 5.30-5.38
(m, 1 H), 4.93-5.09 (m, 2 H), 4.15 (q, J ) 7.1 Hz, 4 H), 2.63 (d, J )
7.6 Hz, 2 H), 1.93-2.03 (m, 6 H), 1.32-1.42 (m, 2 H), 1.21 (t, J ) 7.1
Hz, 6 H), 0.86 (t, J ) 7.4 Hz, 3 H); 13C NMR (50 MHz) δ 171.0 (s),
136.9 (d), 134.5 (d), 133.9 (d), 133.6 (d), 131.4 (d), 129.9 (d), 124.5
(d), 115.2 (t), 61.0 (t), 57.4 (s), 35.9 (t), 34.6 (t), 31.8 (t), 27.0 (t), 22.3
(t), 14.0 (q), 13.6 (q); IR (ATR) 1729 (s, CdO), 1653 (m, CdC), 1602
(w, CdC); HRMS analysis (C21H32O4 ) 348.2321) found m/z 348.2310.
Cyclization of Bisdiene 24b. To a stirred solution of 24b (250.0
mg, 0.74 mmol) in THF (5 mL) was added Pd(OAc)2 (12.2 mg, 0.05
mmol), Ph3P (26-39 mg, 0.10-0.15 mmol), and Et3N (0.35 mL, 2.5
mmol). The resulting mixture was heated to reflux (40 h) to afford,
after chromatography on silica (95:5 Hex:EtOAc), 25b (210 mg,
84%): 1H NMR (500 MHz) δ 6.02 (dd, 1 H, J ) 15.1, 10.3 Hz), 5.99
(ddt, 1 H, J ) 15.1, 10.3, 1.4 Hz), 5.72-5.64 (m, 1 H), 5.63 (dt, 1 H,
J ) 15.1, 7.4 Hz), 5.32 (dd, 1 H, J ) 15.1, 9.1 Hz), 4.96-4.92 (m, 2
H), 4.24-4.20 (m, 2 H), 4.20-4.10 (m, 2 H), 2.37-2.26 (m, 3 H),
2.06 (dq, 2 H, J ) 7.4, 7.4 Hz), 1.93 (dddd, 1 H, J ) 12.3, 12.3, 9.1,
3.6 Hz), 1.78 (dddd, 1 H, J ) 13.8, 3.5, 3.5, 3.5 Hz), 1.72-1.61 (m,
2 H), 1.50 (dd, 1 H, J ) 13.3, 12.3 Hz), 1.25 (t, 3 H, J ) 7.1 Hz), 1.20
(t, 3 H, J ) 7.1 Hz), 1.20-1.10 (m, 1 H), 1.02 (dddd, 1 H, J ) 12.3,
12.3, 12.3, 3.5 Hz), 0.99 (t, 3 H, J ) 7.4 Hz); 13C NMR (50 MHz) δ
172.2 (s), 171.0 (s), 136.7 (d), 134.8 (d), 131.4 (d), 116.0 (t), 61.2 (t),
61.0 (t), 54.8 (s), 42.8 (d), 38.4 (t), 37.8 (t), 30.8 (t), 27.5 (t), 25.5 (t),
14.1 (q), 14.0 (q), 13.5 (q); IR (ATR) 1729 (s, CdO), 1652 (m, CdC),
1640 (m, CdC); HRMS analysis (C21H32O4 ) 348.2301) found m/z
348.2289.
Preparation of 7,7-(Diethylcarboxyl)-1,3,9,11-tridecatetraene (22a).
To a mixture of (E)-(3,5-hexadienyl)propanedioic acid diethyl ester40
(1.780 g, 7.4 mmol) and NaH (300 mg, 12 mmol) in DMSO (60 mL)
was added 2,4-hexadienyl chloride (1.030 g, 8.9 mmol). The resulting
mixture was stirred overnight (12 h), then quenched by the careful
addition of water (50 mL), and extracted with EtOAc (100 mL). The
organic extract washed with saturated aqueous NH4Cl (50 mL) and
brine (2 × 50 mL), then dried (Na2SO4), filtered, and concentrated.
Chromatography on silica afforded bisdiene 22a (2.200 g, 99%): 1H
NMR (360 MHz) δ 6.26-6.84 (m, 1 H), 5.99-6.12 (m, 3 H), 5.61-
5.72 (m, 2 H), 5.33-5.42 (m, 1 H), 4.97-5.14 (m, 2 H), 4.13-4.22
(m, 4 H), 2.67 (d, J ) 7.6 Hz, 2 H), 1.96-2.06 (m, 4 H), 1.74 (d, J )
6.9 Hz, 3 H), 1.26 (t, J ) 7.1 Hz, 6 H); 13C NMR (50 MHz) δ 171.0
(s), 136.9 (d), 134.3 (d), 133.6 (d), 131.4 (d), 131.1 (d), 128.4 (d),
124.3 (d), 115.2 (t), 61.0 (t), 57.3 (s), 35.9 (t), 31.7 (t), 27.0 (t), 17.9
(q), 14.0 (q); IR (ATR) 1726 (s, br. C)O), 1653 (m, CdC), 1602 (m,
CdC); Combustion analysis (C19H28O4 ) 71.22% C, 8.81% H) found
71.11% C, 8.88% H.
Cyclization of Bisdiene 22a. To a stirred solution of 22a (270.0
mg, 0.84 mmol) in THF (5 mL) was added Pd(OAc)2 (12.2 mg, 0.05
mmol), Ph3P (26-39 mg, 0.10-0.15 mmol), and Et3N (0.35 mL, 2.5
mmol). The resulting mixture was heated to reflux (16 h) to afford,
after chromatography on silica (95:5 Hex:EtOAc), 23 (240 mg, 90%):
1H NMR (360 MHz) δ 6.34-6.24 (ddd, 1 H, J ) 17.0, 10.3, 10.3 Hz),
6.06 (dd, 1 H, J ) 15.1, 10.3 Hz), 5.72-5.66 (m, 1 H), 5.45 (dd, 1 H,
J ) 15, 9.0 Hz), 5.13-4.92 (m, 4 H), 4.22 (q, 1 H, J ) 7.2 Hz), 4.20
(q, 1 H, J ) 7.2 Hz), 4.13 (q, 2 H, J ) 7.2 Hz), 2.37-2.23 (m, 3 H),
1.96 (dddd, 1 H, J ) 12.4, 12.4, 9.0, 3.2 Hz), 1.81-1.48 (m, 5 H),
1.26 (t, 3 H, J ) 7.2 Hz), 1.21 (t, 3 H, J ) 7.2 Hz), 1.16-1.25 (m, 1
H); 13C NMR (50 MHz) δ 172.0 (s), 170.8 (s), 137.7 (d), 137.6 (d),
136.9 (d), 136.4 (d), 131.8 (d), 116.0 (t), 115.4 (t), 61.2 (t), 60.9 (t),
54.7 (s), 42.7 (d), 40.6 (d), 38.3 (t), 37.5 (t), 30.7 (t), 27.4 (t), 14.0 (q),
13.9 (q); IR (neat) 1730 (CdO), 1640 (CdC); HRMS analysis
(C19H28O4 ) 320.1984) found m/z 320.1988.
Preparation of N-(2,4-Octadienyl),N-(3,5-hexadienyl), p-Toluene
Sulfonamide (24a). To a cooled (0 °C) solution of (4E)-1,4-octadien-
3-ol (7.80 g, 61.9 mmol) in CH2Cl2 (100 mL) was added SOCl2 (5.0
mL, 69 mmol). The reaction mixture was warmed to room temperature,
stirred for 3 h, and then partitioned with water (100 mL). The aqueous
layer was extracted with EtOAc (50 mL), and the combined organics
were dried (Na2SO4), filtered, and concentrated. The residue was
distilled (aspirator pressure, 70-80 °C) to afford a mixture of octadienyl
chlorides (7.10 g, 85%) which were used without further purification.
To a cooled (-78 °C) solution of (E)-N-(3,5-hexadienyl) p-toluene
sulfonamide (1.310 g, 5.2 mmol) and HMPA (0.25 mL, 13.2 mmol) in
THF (50 mL) was added a solution of n-BuLi (2.50 mL (2.5 M), 6.3
mmol). The resulting mixture was stirred for 0.5 h, and then a solution
of 2,4-octadienyl chloride (0.839 g, 6.2 mmol) in THF (5 mL) was
added. The resulting mixture was slowly warmed to room temperature,
then quenched by the addition of water (50 mL), and concentrated in
vacuo. The residue was extracted with EtOAc (100 mL), and the
organic extract was washed with brine (2 × 50 mL), then dried
(Na2SO4), filtered, and concentrated. Chromatography on silica af-
forded bisdiene 24a (0.750 g, 41%): 1H NMR (360 MHz) δ 7.68 (d,
J ) 8.1 Hz, 2 H), 7.27 (d, J ) 8.1 Hz, 2 H), 6.26 (ddd, J ) 16.9, 10.1,
10.1 Hz, 1 H), 5.91-6.10 (m, 2 H), 5.66 (dt, J ) 14.9, 6.9 Hz, 1 H),
5.55 (dt, J ) 15.3, 7.0 Hz, 1 H), 5.33 (dt, J ) 14.8, 6.8 Hz, 1 H), 5.10
(d, J ) 16.9 Hz, 1 H), 5.00 (d, J ) 10.1 Hz, 1 H), 3.81 (d, J ) 6.9 Hz,
2 H), 3.16 (t, J ) 7.3 Hz, 2 H), 2.41 (s, 3 H), 2.26-2.33 (m, 2 H),
2.00-2.06 (m, 2 H), 1.36-1.42 (m, 2 H), 0.89 (t, J ) 7.3 Hz, 3 H);
13C NMR (50 MHz) δ 142.8 (s), 137.0 (s), 136.6 (d), 135.5 (d), 134.2
(d), 132.9 (d), 130.4 (d), 129.4 (d), 128.9 (d), 126.9 (d), 124.7 (d),
115.6 (t), 49.7 (t), 46.4 (t), 34.4 (t), 31.6 (t), 22.1 (t), 21.2 (q), 13.4
(q); IR (ATR) 1653 (m, CdC), 1599 (m, Ar), 1338 (s, SO2), 1154 (s,
Preparation of (8E)-1,8,10-Undecatrien-3-ol. To a cooled (0 °C)
solution of (6E)-6,8-nonadienal40,42 (4.40 g, 31.9 mmol) in THF (75
mL) was added vinylmagnesium bromide (1.0 M, 35.0 mL, 35.0 mmol).
After 2 h, the mixture was quenched by the addition of water (75 mL)
and partitioned with ether (3 × 100 mL). The combined organic layers
were dried (MgSO4), filtered, and concentrated. Chromatography on
silica (230-400 mesh, 80:20 Hex:EtOAc) afforded the allylic alcohol
(4.21 g, 80%): TLC analysis (80:20 Hex:EtOAc) Rf 0.4; 1H NMR (300
MHz) δ 6.40-6.16 (m, 1 H), 6.11-5.93 (m, 1 H), 5.91-5.67 (m, 2
H), 5.26-4.84 (m, 4 H), 4.17-3.94 (m, 1 H), 2.53-1.93 (m, 2 H),
1.62-1.12 (m, 6 H); 13C NMR (75 MHz) δ 141.2 (d), 137.1 (d), 134.9
(d), 130.9 (d), 114.5 (t), 114.3 (t), 72.8 (d), 36.6 (t), 32.3 (t), 28.9 (t),
24.7 (t); IR (ATR) 3650-3200 (OH, 55); Combustion analysis (C11H18O
) 79.46% C, 10.91% H) found 79.69% C, 10.75% H.
(42) Craig, D.; Geach, N. J.; Pearson, C. J.; Slawin, A. M. Z.; White, A.
J. P.; Williams, D. J. Tetrahedron 1995, 51, 6071-98.