Pd-Catalyzed Coupling to Benzofurans and Isocoumarins
112.4 (d, J ) 181.0 Hz), 113.7, 125.3, 129.9, 131.8 (d, J ) 22.6
Hz), 134.3 (d, J ) 8.3 Hz), 160.1 (d, J ) 15.3 Hz); 31P NMR (160
MHz, CDCl3) δ 12.6; LC/MS (Rt 0.96 min) m/z 309 [M + 1]+.
Anal. Calcd for C16H21O4P: C, 62.33; H, 6.86. Found: C, 62.28;
H, 6.86.
Compound 11: Yield 60% (purity ∼97%) gummy solid; IR
(KBr, cm-1) ν 3468, 3345, 3227, 1609, 1514, 1265, 1182, 1059,
1007; 1H NMR (400 MHz, CDCl3) δ 1.01, 1.13 (2s, 6H), 3.87 (dd
f t, J ∼ 10.2 Hz each, 2H), 4.13 (dd, J ∼ 10.2, 13.3 Hz, 2H),
5.44 (d, J ) 17.2 Hz, 1H), 5.58 (br, J ) 9.2 Hz, dCHcisHtrans, 1H),
5.59 (d, J ) 17.2 Hz, dCHcisHtrans, 1H), 6.64 (d, J ) 8.0 Hz, 2H),
7.15 (d, J ) 8.0 Hz, 2H), 7.40 (not resolved, m, 1H); 13C NMR
(50 MHz, CDCl3) δ 21.4, 21.7, 32.5 (d, J ) 6.0 Hz), 75.6 (d, J )
6.0 Hz), 110.7 (d, J ) 181.9 Hz), 114.5, 125.0, 128.7, 129.9, 132.0,
132.2, 134.4 (d, J ) 9.7 Hz) 147.6, 160.5 (d, J ) 7.2 Hz); 31P
NMR (160 MHz, CDCl3) δ 13.4; LC/MS (Rt 0.71 min) m/z 294
[M + 1]+.
General Procedure for Preparation of 12-15: A 25 mL round-
bottomed flask containing allenylphosphonate 1c (0.300 g, 1.38
mmol), Pd(OAc)2 (0.015 g, 0.069 mmol), PPh3 (0.054 g, 0.207
mmol), iodobenzene (0.339 g, 1.66 mmol), and K2CO3 (0.381 g,
2.76 mmol) was purged with nitrogen gas several times. To the
flask was then added dry DMF (5 mL). The contents were heated
at 80-90 °C for 18-24 h. The reaction mixture was quenched
with water, extracted with ether (3 × 20 mL), dried (Na2SO4),
filtered, and concentrated under vacuum. The residue was subjected
to column chromatography (hexane/EtOAc, 55/45) to afford the
desired product 12. For the preparation of compounds 13-15,
similar molar quantities of the respective allenes were used.
Conditions used for optimization are given in Table 1.
Compound 12: Yield 0.31 g (75%); mp 136-138 °C; IR (KBr,
cm-1) ν 1586, 1476, 1267, 1061, 1007; 1H NMR (400 MHz, CDCl3)
δ 0.82, 1.08 (2s, 6H), 2.04 (s, 3H), 3.60-3.76 (m, 4H), 4.92, 5.36
(2s, 2H), 5.84 (d, J ) 16.0 Hz, 1H), 7.26-7.39 (m, 5H); 13C NMR
(100 MHz, CDCl3) δ 20.6, 21.0, 21.7, 32.2 (d, J ) 6.2 Hz), 75.9
(d, J ) 6.0 Hz), 112.0 (d, J ) 183.1 Hz), 123.3, 127.7, 127.9,
128.4 129.0, 137.4 (d, J ) 8.0 Hz), 144.0 (d, J ) 21.9 Hz), 161.8
(d, J ) 5.6 Hz); 31P NMR (80 MHz, CDCl3) δ 11.5; LC/MS (Rt
0.72 min) m/z 293 [M + 1]+. Anal. Calcd for C16H21O3P: C, 65.75;
H, 7.19. Found: C, 65.58; H, 7.13. An X-ray structure was
performed on this sample.
(80 MHz, CDCl3) δ 12.4; LC/MS (Rt 0.70 min): 308 [M]+. Anal.
Calcd for C16H22NO3P: C, 62.54; H, 7.16; N, 4.56. Found: C,
62.59; H, 7.17; N, 4.52.
Compound 16: This compound was prepared by reacting 1b
(0.30 g, 1.48 mmol) with an excess (3 molar equiv) of iodobenzene
by using a procedure similar to that for 8: Yield quantitative; mp
126-128 °C; IR (KBr, cm-1) ν 1615, 1560, 1491, 1343, 1310,
1
1242, 1059, 1009; H NMR (400 MHz, CDCl3) δ 1.05, 1.16 (2s,
6H), 3.92 (dd f t, J ∼ 10.8 Hz each, 2H), 4.18 (dd f t, J ∼ 12.2
Hz each, 2H), 5.62 (d, J ) 17.8 Hz, 1H), 6.60 (d, J ) 16.0 Hz,
1H), 7.26-7.47 (m, 10H), 8.02 (d, J ) 16.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 21.4, 21.7, 32.6 (d, J ) 5.9 Hz), 75.7 (d, J
) 5.9 Hz), 112.8 (d, J ) 180.5 Hz), 126.0, 126.1, 127.6, 128.4,
128.6, 128.7, 128.8, 129.0, 136.1, 139.7, 140.1, 140.3, 160.7 (d, J
) 6.1 Hz); 31P NMR (160 MHz, CDCl3) δ 11.6. X-ray structure
was determined for this compound.
Preparation of 17: A 25 mL round-bottomed flask containing
allenylphosphonate 1c (0.45 g, 2.08 mmol), Pd(OAc)2 (0.023 g,
0.104 mmol), PPh3 (0.082 g, 0.312 mmol), 2-nitroiodobenzene
(0.662 g, 2.49 mmol), and K2CO3 (0.575 g, 4.16 mmol) was purged
with nitrogen gas several times. Dry acetonitrile (10 mL) was then
added, and the contents were heated under reflux for 48 h. TLC
[Rf ) 0.19 (hexane/EtOAc, 50/50)] and 31P NMR showed only 10%
product formation. More Pd(OAc)2 (0.022 g, 0.09 mmol) was added,
and the reaction continued for 48 h more. Then the reaction mixture
was quenched with water, extracted with ether (3 × 20 mL), dried
(Na2SO4), filtered, and concentrated under vacuum. The residue
was subjected to column chromatography (hexane/EtOAc, 50/50)
to afford product 17: Yield 0.47 g (50%) (remaining was unreacted
allene); mp 190-192 °C; IR (KBr, cm-1) ν 1520, 1474, 1343, 1263,
1
1059, 1006, 820; H NMR (400 MHz, CDCl3) δ 0.89, 1.06 (2s,
6H), 2.06 (s, 3H), 3.67-3.99 (m, 4H), 6.12 (d, J ) 15.3 Hz, 1H),
6.37 (s, 1H), 7.26 (d, J ) 6.0 Hz, 1H), 7.43 (t, J ) 7.3 Hz, 1H),
7.60-7.65 (m, 3H), 7.74 (t, J ) 7.3 Hz, 1H), 8.05 (d, J ) 8.0 Hz,
1H), 8.24 (d, J ) 8.0 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 16.0,
21.1, 21.6, 32.4 (d, J ) 6.6 Hz), 75.8 (br), 112.9 (d, J ) 185.6
Hz), 124.9, 128.6, 130.0, 131.5, 131.8, 132.7, 133.2, 133.7, 137.5,
147.5 (d, J ) 15.7 Hz), 159.7; 31P NMR (160 MHz, CDCl3) δ
11.0. Anal. Calcd for C22H23O7N2P: C, 57.64; H, 5.05; N, 6.11.
Found: C, 57.78; H, 5.05; N, 6.11. X-ray structure was determined
for this compound.
Compound 13: Yield 76%; mp 158-159 °C; IR (KBr, cm-1) ν
1582, 1462, 1265, 1111, 1057, 1001; 1H NMR (400 MHz, CDCl3)
δ 0.82, 1.10 (2s, 6H), 2.03 (s, 3H), 2.36 (s, 3H), 3.62-3.76 (m,
4H), 4.95 (s, 1H), 5.34 (s, 1H), 5.81 (d, J ) 16.8 Hz, 1H), 7.15-
7.27 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 20.7, 21.0, 21.4,
21.8, 32.2 (d, J ) 7.0 Hz), 75.8 (d, J ) 6.0 Hz), 111.5 (d, J )
183.0 Hz), 123.0, 128.4, 128.9, 134.4, 138.3, 144.1 (d, J ) 22.0
Hz), 162.3; 31P NMR (160 MHz, CDCl3) δ 12.8. LC/MS (Rt 0.71
min) m/z 307 [M + 1]+. Anal. Calcd for C17H23O3P: C, 66.66; H,
7.52. Found: C, 66.67; H, 7.54.
Preparation of 18: A 25 mL round-bottomed flask containing
allene 2b (0.279 g, 1.94 mmol), Pd(OAc)2 (0.021 g, 0.09 mmol),
PPh3 (0.074 g, 0.29 mmol), iodobenzene (0.475 g, 2.33 mmol),
and K2CO3 (0.525 g, 3.88 mmol) was purged with nitrogen gas
several times. Dry acetonitrile (4 mL) was then added. The contents
were refluxed for 12 h. The reaction mixture was quenched with
water, extracted with ether (3 × 20 mL), dried (Na2SO4), filtered,
and concentrated under vacuum. The residue was subjected to
column chromatography (hexane) to afford the desired product 18.
It was finally purified (∼95% purity) by vacuum distillation (oil
bath temperature ∼80 °C/0.5 mm): Yield 0.298 g (70%); IR (neat,
Compound 14: Yield 77%; mp 128-130 °C; IR (KBr, cm-1) ν
1
cm-1) ν 1672, 1602, 1491, 1445, 1367, 1074, 897, 756, 696; H
1
1613, 1580, 1466, 1265, 1175, 1061, 1007; H NMR (400 MHz,
NMR (400 MHz, CDCl3) δ 2.16 (s, 3H), 4.72 (s, 1H), 5.14 (s,
1H), 6.74 (s, 1H), 6.90-7.37 (m, 10H); 13C NMR (50 MHz, CDCl3)
δ 21.1, 117.5, 126.6, 127.0, 127.1, 127.9, 128.5, 129.6, 130.0, 137.2,
139.9, 143.6, 145.4 [lit16: 1H NMR (CDC13) δ 2.16 (s, 3H), 4.80
(s, 1H), 5.21 (s, 1H), 6.87 (s, 1H), 6.90-7.20 (m, 10H); 13C NMR
(CDCl3) δ 21.08, 117.44, 126.57, 126.99, 127.09, 127.83, 128.24,
128.47, 129.01, 129.52, 129.96, 131.61]; GC-MS (Rt 4.09 min;
column temperature 200 °C) m/z 220 [M]+.
CDCl3) δ 0.82, 1.10 (2s, 6H), 2.02 (s, 3H), 3.62-3.76 (m, 4H),
3.82 (s, 3H), 4.97 (s, 1H), 5.34 (s, 1H), 5.78 (d, J ) 16.6 Hz, 1H),
6.88 (d, J ) 8.6 Hz, 2H), 7.26 (d, J ) 8.6 Hz, 2H); 13C NMR (50
MHz, CDCl3) δ 20.8, 21.0, 21.8, 32.2 (d, J ) 7.3 Hz), 55.1, 75.8
(d, J ) 5.8 Hz), 111.4 (d, J ) 180.7 Hz), 113.2, 122.4, 130.5,
143.5, 144.0, 159.9, 162.0; 31P NMR (160 MHz, CDCl3) δ 13.0.
LC/MS (Rt 0.69 min) m/z 323 [M + 1]+. Anal. Calcd for
C17H23O4P: C, 63.35; H, 7.14. Found: C, 63.42; H, 7.15.
Compound 15: Yield 70%; mp 158-160 °C; IR (KBr, cm-1) ν
Preparation of 19: This compound was prepared by using a
procedure similar to that for 18 by the use of 2d (0.108 g, 0.77
mmol). The compound was purified by column chromatography
1
3453, 3360, 3242, 1611, 1574, 1248, 1173, 1057, 1005; H NMR
(400 MHz, CDCl3) δ 0.82, 1.14 (2s, 6H), 2.01 (s, 3H), 3.63-3.75
(m, 4H), 5.05 (s, 1H), 5.32 (s, 1H), 5.72 (d, J ) 16.7 Hz, 1H),
6.66 and 7.16 (2d, J ) 7.9 Hz each, 4H); 13C NMR (50 MHz,
CDCl3) δ 21.0, 21.8 (2s, CH3 and another CH3, merged with δ
20.9), 32.2 (br), 75.8 (d, J ) 5.8 Hz), 110.3 (d, J ) 181.8 Hz),
114.2, 121.8, 130.5, 144.9 (d, J ) 22.3 Hz), 147.1, 162.4; 31P NMR
(hexane) to afford 19: Yield 0.132 g (80%) (oil); IR (KBr, cm-1
)
ν 1726, 1711, 1597, 1445, 1370, 1262, 1161, 1038; 1H NMR (400
MHz, CDCl3) δ 1.06 (t, J ) 7.1 Hz, 3H), 2.06 (s, 3H), 4.00 (q, J
) 7.1 Hz, 2H), 4.87 (s, 1H), 5.36 (s, 1H), 6.08 (s, 1H), 7.11-7.37
(m, 5H); 13C NMR (50 MHz, CDCl3) δ 14.0, 20.6, 59.9, 117.2,
J. Org. Chem, Vol. 71, No. 24, 2006 9135