Stille ± Heck Couplings
4035±4046
17.2 ( ), 18.1 (Cq), 25.8 (), 27.6 ( ), 33.4 ( ), 51.7 (), 72.3 (), 120.4 (),
133.3 (Cq), 134.9 (Cq), 144.7 (), 167.2 (Cq); MS (EI): m/z (%): 361/359 (2/2)
2.26 (m, 2H), 2.34 (m, 2H), 4.27 (d, 3J(H,H) 6 Hz, 2H), 5.81 (d,
3J(H,H) 16 Hz, 1H), 5.97 (dt, 3J(H,H) 6, 3J(H,H) 16 Hz, 1H), 7.02 (d,
3J(H,H) 16 Hz, 1H), 7.98 (d, 3J(H,H) 16 Hz, 1H); 13C NMR: d 22.1
[M CH3] , 319/317 (100/98) [M C4H9] ; elemental analysis calcd (%)
for C16H27BrO3Si (375.4): C 51.20, H 7.25; found: C 51.49, H 7.36.
(
), 26.0 ( ), 27.1 ( ), 28.2 (), 29.7 ( ), 64.1 ( ), 80.2 (Cq), 118.2 (),
128.2 (), 129.7 (), 131.3 (Cq), 139.4 (Cq), 140.3 (), 167.3 (Cq); MS (EI):
Methyl (E)-3-{2-[(E)-2-tert-butoxycarbonylethenyl]-3-(tert-butyldimethyl-
silyloxy)cyclohex-1-enyl}acrylate (19): According to GP 1, the bromoenol
m/z (%): 264 (3) [M] , 190 (52) [M C4H10O] , 145 (98) [M
CO2C(CH3)3 H2O] , 57 (84) [C(CH3)3] ; C16H24O3 (264.4).
triflate
7 (121 mg, 0.275 mmol) was treated with Pd(OAc)2 (4.3 mg,
19 mmol), PPh3 (10 mg, 38 mmol), LiCl (35 mg, 0.83 mmol), and methyl
(E)-3-(tributylstannyl)acrylate (155 mg, 0.413 mmol) in DMF (10 mL) for
40 h at 458C (Stille coupling). For the Heck coupling, Pd(OAc)2 (4.3 mg,
19 mmol), PPh3 (10 mg, 38 mmol), NEt3 (77 mL, 0.55 mmol), and tert-
butylacrylate (88 mg, 0.69 mmol) were added, and the reaction mixture was
stirred for 39 h at 908C. Workup A and column chromatography on
aluminum oxide [80 g, 3% H2O, PE/Et2O 10:1 (440 mL), then PE/EtOAc
10:1] yielded the tert-butyl (E)-3-{2-[(E)-2-tert-butoxycarbonylethenyl]-3-
(tert-butyldimethylsilyloxy)cyclohex-1-enyl}acrylate (18a) (Rf 0.31, PE/
Et2O 10:1) as a colorless solid (4 mg, 3%), hexatriene 19 (Rf 0.19, PE/
Et2O 10:1) as a colorless oil (54 mg, 46%) and methyl (E)-3-{2-[(E)-2-
methoxycarbonylethenyl]-3-(tert-butyldimethylsilyloxy)cyclohex-1-enyl}-
acrylate (18b) (Rf 0.10, PE/Et2O 10:1) as a colorless solid (14 mg, 13%).
tert-Butyl (E)-3-(bicyclohexyl-1,1'-dien-2-yl)acrylate (24a): According to
GP 1 the bromoenol triflate 11 (309 mg, 1.00 mmol) was treated with
[Pd2(dba)3] ´ CHCl3 (104 mg, 0.100 mmol), AsPh3 (25 mg, 82 mmol), LiCl
(127 mg, 3.00 mmol), CuI (10 mg, 53 mmol), and tributyl(cyclohex-1-
enyl)stannane (23, 390 mg, 1.05 mmol) in DMF (10 mL) for 4 h at 658C
(Stille coupling). For the Heck coupling, Pd(OAc)2 (16 mg, 71 mmol), PPh3
(55 mg, 0.21 mmol), NEt3 (202 mg, 2.00 mmol), and tert-butyl acrylate
(320 mg, 2.50 mmol) were added, and the reaction mixture was stirred for
39 h at 958C. Due to incomplete conversion and decomposition of the
catalyst a second portion of Pd(OAc)2 (16 mg, 71 mmol) and PPh3 (55 mg,
0.21 mmol) was added, and the reaction mixture was stirred for 45 h at
958C. Workup A and column chromatography on silica gel (60 g, pentane/
Et2O 30:1) afforded 2-bromobicyclohex-1-enyl (25, 133 mg, 55%) (Rf
0.74, pentane) and hexatriene 24a (117 mg, 41%) (Rf 0.46) as colorless
oils.
1
1
Compound 19: IR (film): nÄ 1721 cm (C O); H NMR: d 0.11 (s, 6H),
0.85 (s, 9H), 1.49 (s, 9H), 1.58 ± 1.96 (m, 4H), 2.12 ± 2.25 (m, 1H), 2.35 ± 2.46
3
1
Compound 24a: IR (film): nÄ 1704 cm (C O); 1H NMR: d 1.41 (s,
(m, 1H), 3.76 (s, 3H), 4.51 (m, 1H), 5.96 (d, J(H,H) 15.8 Hz, 1H), 6.01
(d, 3J(H,H) 15.8 Hz, 1H), 7.65 (d, 3J(H,H) 15.8 Hz, 1H), 7.90 (d,
3J(H,H) 15.8 Hz, 1H); 13C NMR: d 4.8 (), 4.0 (), 16.4 ( ), 18.1
(Cq), 25.7 (), 26.4 ( ), 28.1 (), 31.4 ( ), 51.6 (), 66.0 (), 80.3 (Cq),
119.7 (), 123.9 (), 136.7 (Cq), 139.1 (), 140.2 (Cq), 141.4 (), 166.0 (Cq),
9H), 1.49 ± 1.66 (m, 8H), 1.95 (m, 2H), 2.07 (m, 6H), 5.32 (m, 1H), 5.59 (d,
3J(H,H) 18 Hz, 1H), 7.59 (d, 3J(H,H) 18 Hz, 1H); 13C NMR: d 22.1
(
(
), 22.3 ( ), 22.4 ( ), 22.5 ( ), 22.8 ( ), 25.2 ( ), 26.0 ( ), 28.2 (), 30.6
), 79.5 (Cq), 115.9 (), 126.2 (), 127.3 (Cq), 138.6 (Cq), 144.3 (), 150.6
167.2 (Cq); MS (DCI, NH3): m/z (%): 440 (100) [MNH4] , 291 (72) [M
(Cq), 167.5 (Cq); MS (EI): m/z (%): 288 (2) [M] , 232 (73) [M C4H8] , 187
OSi(CH3)2C4H9] ; C23H38O5Si (422.6).
(100) [M CO2C(CH3)3] , 145 (45) [M CO2C(CH3)3 C3H6] ; elemental
analysis calcd (%) for C19H28O2 (288.4): C 79.12, H 9.78; found: C 78.98, H
9.79.
Compound 18b: M.p. 898C; 1H NMR: d 0.10 (s, 3H), 0.11 (s, 3H), 0.84 (s,
9H), 1.56 ± 1.72 (m, 2H), 1.82 ± 1.94 (m, 2H), 2.13 ± 2.27 (m, 1H), 2.37 ± 2.50
(m, 1H), 3.76 (s, 3H), 3.77 (s, 3H), 4.53 (m, 1H), 6.04 (d, 3J(H,H) 15.7 Hz,
2H), 7.78 (d, 3J(H,H) 15.8 Hz, 1H), 7.91 (d, 3J(H,H) 15.7 Hz, 1H);
elemental analysis calcd (%) for C20H32O5Si (380.6): C 63.12, H 8.48; found:
C 63.44, H 8.52.
Compound 25: 1H NMR: d 1.65 (m, 8H), 2.17 (m, 4H), 2.19 (m, 2H), 2.51
(m, 2H), 5.42 (m, 1H); 13C NMR: d 22.0 ( ), 22.6 ( ), 22.8 ( ), 24.7 ( ),
25.0 ( ), 26.6 ( ), 31.9 ( ), 36.3 ( ), 117.6 (Cq), 124.1 (), 140.0 (Cq), 140.2
(Cq); MS (EI): m/z (%): 242/240 (70/64) [M] , 161 (100) [M Br] ; analysis
Compound 18a: M.p. 548C; 1H NMR: d 0.08 (s, 6H), 0.83 (s, 9H), 1.44 ±
1.65 (m, 2H), 1.47 (s, 18H), 1.78 ± 1.94 (m, 2H), 2.06 ± 2.22 (m, 1H), 2.30 ±
2.42 (m, 1H), 4.48 (m, 1H), 5.91 (d, 3J(H,H) 15.7 Hz, 1H), 5.92 (d,
3J(H,H) 15.8 Hz, 1H), 7.61 (d, 3J(H,H) 15.8 Hz, 1H), 7.79 (d, 3J(H,H)
15.7 Hz, 1H); elemental analysis calcd (%) for C26H44O5Si (464.7): C 67.20,
H 9.54; found: C 67.48, H 9.55.
calcd for C12H17Br: 240.0513 (correct mass according to HRMS).
Methyl (E)-3-[2-(4,5-dihydrofuran-2-yl)cyclohex-1-enyl]acrylate (26b):
According to GP 1 the bromoenol triflate 11 (309 mg, 1.00 mmol) was
treated with [Pd(dba)2] (12 mg, 21 mmol), TFP (10 mg, 43 mmol), ZnCl2
(300 mg, 2.20 mmol), and tributyl(4,5-dihydrofuran-2-yl)stannane (467 mg,
1.30 mmol) in DMF (16 mL) for 19 h at 408C (Stille coupling). For the Heck
coupling, Pd(OAc)2 (16 mg, 71 mmol), PPh3 (55 mg, 0.21 mmol), LiCl
(127 mg, 3.00 mmol), NEt3 (202 mg, 2.00 mmol), and methyl acrylate
(215 mg, 2.50 mmol) were added, and the reaction mixture was stirred for
29 h at 958C. Workup A and column chromatography on aluminum oxide
(100 g, 5% H2O, pentane/Et2O 10:1) afforded hexatriene 26b (Rf 0.25) as
tert-Butyl
(E)-3-{[(E)-2-trimethylsilylethenyl]cyclohex-1-enyl}acrylate
(20a): According to GP 1, the bromoenol triflate 11 (309 mg, 1.00 mmol)
was treated with [Pd(PPh3)4] (58 mg, 50 mmol), LiCl (127 mg, 3.00 mmol),
and tributyl[(E)-2-trimethylsilylethenyl]stannane (408 mg, 1.05 mmol) in
DMF (16 mL) for 20 h at 908C (Stille coupling). For the Heck coupling,
Pd(OAc)2 (16 mg, 71 mmol), PPh3 (55 mg, 0.21 mmol), NEt3 (202 mg,
2.00 mmol), and tert-butyl acrylate (215 mg, 1.68 mmol) were added, and
the reaction mixture was stirred for 24 h at 908C. Workup A and column
chromatography on silica gel (70 g, pentane/Et2O 30:1) afforded the
hexatriene 20a (Rf 0.57) as a colorless solid (234 mg, 76%). M.p. 748C;
1
1
a colorless oil (150 mg, 64%). IR (film): nÄ 1718 cm (C O); H NMR:
d 1.65 (m, 4H), 2.27 (m, 4H), 2.72 (dt, 3J(H,H) 2, 3J(H,H) 9 Hz, 2H),
3.72 (s, 3H), 4.38 (t, 3J(H,H) 9 Hz, 2H), 4.94 (t, 3J(H,H) 2 Hz, 1H), 5.97
(d, 3J(H,H) 17 Hz, 1H), 7.14 (d, 3J(H,H) 17 Hz, 1H); 13C NMR: d
22.0 ( ), 22.1 ( ), 25.9 ( ), 29.0 ( ), 30.5 ( ), 51.4 (), 69.7 ( ), 102.1 (),
115.5 (), 132.2 (Cq), 135.6 (Cq), 144.7 (), 156.1 (Cq), 168.3 (Cq); MS (EI):
1
1
IR (KBr): nÄ 1706 cm (C O); H NMR: d 0.11 (s, 9H), 1.51 (s, 9H),
3
m/z (%): 234 (30) [M] , 175 (100) [M CO2CH3] , 133 (32) [M
1.64 (m, 4H), 2.26 (m, 2H), 2.34 (m, 2H), 5.79 (d, J(H,H) 16 Hz, 1H),
6.11 (d, 3J(H,H) 16 Hz, 1H), 7.29 (d, 3J(H,H) 16 Hz, 1H), 8.07 (d,
3J(H,H) 16 Hz, 1H); 13C NMR: d 1.2 (), 22.1 ( ), 22.2 ( ), 26.2 ( ),
26.6 ( ), 28.2 (), 80.0 (Cq), 118.3 (), 131.3 (), 131.5 (Cq), 139.8 (),
CO2CH3 C3H6] ; anal. calcd for C14H18O3: 234.1255 (correct mass
according to HRMS).
tert-Butyl (E)-3-{2-[5,6-dihydro-4H-pyran-2-yl]cyclohex-1-enyl}acrylate
(27a): According to GP 1, the bromoenol triflate 11 (309 mg, 1.00 mmol)
was treated with [Pd(dba)2] (12 mg, 21 mmol), TFP (10 mg, 43 mmol), ZnCl2
(300 mg, 2.20 mmol), and tributyl(5,6-dihydro-4H-pyran-2-yl)stannane
(485 mg, 1.30 mmol) in DMF (16 mL) for 26 h at 258C (Stille coupling).
For the Heck coupling, Pd(OAc)2 (16 mg, 71 mmol), PPh3 (55 mg,
0.21 mmol), LiCl (127 mg, 3.00 mmol), NEt3 (202 mg, 2.00 mmol), and
tert-butyl acrylate (320 mg, 2.50 mmol) were added, and the reaction
mixture was stirred for 35 h at 958C. Workup A and column chromatog-
raphy on aluminum oxide (100 g, 5% H2O, pentane/Et2O 15:1) yielded
hexatriene 27a (Rf 0.26) as a colorless oil (256 mg, 88%). IR (film): nÄ
140.2 (), 141.0 (Cq), 167.1 (Cq); MS (EI): m/z (%): 306 (9) [M] , 205 (21)
[M CO2C4H9] , 73 (100) [Si(CH3)3] , 57 (20) [C4H9] ; elemental analysis
calcd (%) for C18H30O2Si (306.5): C 70.54, H 9.87; found: C 70.89, H 9.58.
tert-Butyl
(E)-3-{2-[(E)-3-hydroxyprop-1-enyl]cyclohex-1-enyl}acrylate
(21a): According to GP 1 the bromoenol triflate 11 (155 mg, 0.500 mmol)
was treated with Pd(OAc)2 (8.0 mg, 36 mmol), PPh3 (27 mg, 0.10 mmol),
LiCl (64 mg, 1.5 mmol), and tributyl[(E)-3-hydroxyprop-1-enyl]stannane
(226 mg, 0.651 mmol) in DMF (8 mL) for 50 h at 658C (Stille coupling). For
the Heck coupling Pd(OAc)2 (8.0 mg, 36 mmol), PPh3 (27 mg, 0.10 mmol),
NEt3 (101 mg, 1.00 mmol), and tert-butyl acrylate (162 mg, 1.26 mmol) were
added, and the reaction mixture was stirred for 24 h at 908C. Workup A and
column chromatography on silica gel (40 g, PE/Et2O 1:1) yielded hexa-
1
1
1705 cm (C O); H NMR: d 1.49 (s, 9H), 1.64 (m, 4H), 1.85 (m, 2H),
2.09 ± 2.22 (m, 4H), 2.30 (m, 2H), 4.03 (m, 2H), 4.66 (t, 3J(H,H) 4 Hz,
1H), 5.71 (d, 3J(H,H) 15 Hz, 1H), 7.85 (d, 3J(H,H) 15 Hz, 1H);
13C NMR: d 20.6 ( ), 22.1 ( ), 22.2 ( ), 22.3 ( ), 25.3 ( ), 28.2 (),
1
triene 21a (Rf 0.42) as a yellow oil (89 mg, 67%). IR (film): nÄ 3429 cm
1
(OH), 1704 (C O); H NMR: d 1.50 (s, 9H), 1.66 (m, 4H), 2.16 (brs, 1H),
Chem. Eur. J. 2001, 7, No. 18
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0718-4043 $ 17.50+.50/0
4043