Palladium-Catalyzed Carbonylative Coupling Reactions
FULL PAPER
an Agilent HP-5890 instrument with a FID detector, a HP-5 capillary
column (polydimethylsiloxane with 5% phenyl groups, length: 30 m, in-
ternal diameter: 0.32 mm, film thickness: 0.25 mm), and argon as the car-
rier gas. GCMS was carried out on an Agilent HP-5890 instrument with
an Agilent HP-5973 Mass-Selective Detector (EI), a HP-5 capillary
column (polydimethylsiloxane with 5% phenyl groups, length: 30 m, in-
ternal diameter: 0.25 mm, film thickness: 0.25 mm), and helium as the car-
rier gas. MS (ESI) was performed on an Agilent 1969A TOF mass spec-
trometer.
125.1, 99.1, 34.9, 31.1 ppm; GCMS (EI, 70 eV): m/z (%): 304 (100) [M]+,
289 (60), 161 (60), 115 (30), 91 (10).
(E)-3-Benzylidene-5-(naphthalen-1-yl)furan-2ACTHNUTRGNEUG(N 3H)-one:
1H NMR (300 MHz, CDCl3): d=8.30 (d, J=8.6 Hz, 1H), 7.73–7.84 (m,
3H), 7.27–7.58 (m, 9H), 6.85 ppm (d, J=1.0 Hz, 1H); 13C NMR
(75 MHz, CDCl3): d=169.4, 157.3, 136.0, 135.2, 133.9, 131.3, 130.4, 130.3,
130.2, 129.2, 129.0, 127.4, 127.2, 126.4, 126.1, 125.3, 125.2, 104.7 ppm;
GCMS (EI, 70 eV): m/z (%): 298 (100) [M]+, 269 (30), 220 (15), 155 (80),
127 (85).
Typical procedure: PdACHTUNGTRENNUNG(OAc)2 (2 mol%) and TFP (4 mol%) were trans-
(E)-3-Benzylidene-5-(naphthalen-2-yl)furan-2ACTHNUTRGNEUG(N 3H)-one:
1H NMR (300 MHz, CDCl3): d=8.18 (s, 1H), 7.66–7.83 (m, 4H), 7.55–
7.61 (m, 2H), 7.36–7.48 (m, 6H), 6.95 ppm (br s, 1H); 13C NMR
(75 MHz, CDCl3): d=169.4, 157.0, 135.5, 135.2, 134.2, 133.1, 130.4, 130.2,
129.2, 128.9, 128.8, 127.9, 127.6, 127.0, 125.7, 125.5, 125.2, 122.0,
100.5 ppm; GCMS (EI, 70 eV): m/z (%): 298 (85) [M]+, 281 (25), 207
(100), 155 (95), 127 (70), 96 (10).
ferred into a vial (reaction volume: 4 mL) that was equipped with a
septum, a small cannula, and a stirrer bar. After the vial was purged with
argon, iodobenzene (1 mmol), benzyl acetylene (1 mmol), THF (2 mL),
and DiPEA (2 mmol) were injected into the vial by using a syringe.
Then, the vial was placed on an alloy plate that was transferred into an
autoclave (300 mL, 4560 series Parr Instruments) under an argon atmos-
phere. After flushing the autoclave three times with CO, the pressure
was adjusted to 1 bar, and the reaction was performed for 20 h at 258C.
After this time, the pressure was carefully released. Water (6 mL) was
added to the mixture and the solution was extracted 3–5 times with
EtOAc (2–3 mL). The extracts were evaporated by adsorption onto silica
gel and the crude product was purified by column chromatography (n-
heptane to n-heptane/EtOAc, 10:1). The product was obtained as a
yellow solid (248 mg, 98% yield).
(E)-3-Benzylidene-5-(4-methoxyphenyl)furan-2ACTHNUTRGNEUG(N 3H)-one:
1H NMR (300 MHz, CDCl3): d=7.50–7.66 (m, 4H), 7.26–7.42 (m, 4H),
6.84–6.92 (m, 2H), 6.72 (d, J=0.94 Hz, 1H), 3.78 ppm (s, 3H); 13C NMR
(75 MHz, CDCl3): d=169.7, 161.6, 157.0, 135.4, 133.9, 130.0, 129.1, 127.1,
125.7, 120.7, 114.5, 98.0, 55.5 ppm; GCMS (EI, 70 eV): m/z (%): 278 (65)
[M]+, 207 (40), 135 (100), 77 (10).
(E)-3-Benzylidene-5-(4-bromophenyl)furan-2ACTHNUTRGNEUG(N 3H)-one:
1H NMR (300 MHz, CDCl3): d=7.47–7.57 (m, 6H), 7.33–7.41 (m, 4H),
6.86 ppm (d, J=0.9 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=169.1,
155.9, 136.2, 135.1, 132.3, 130.5, 130.2, 129.2, 127.0, 126.8, 125.2, 124.9,
100.4 ppm; GCMS (EI, 70 eV): m/z (%): 328 (80), 327 (80) [M]+, 185
(100), 183 (100), 157 (20), 155 (20), 115 (10), 76 (10).
Computational details: On the basis of our previous computational inves-
tigations into the competitive Heck and carbonylative Heck reaction,[7k]
for geometry optimization and the frequency calculations, we decided to
use the BP86 functional[12] in combination with the all-electron TZVP[13]
basis set for C, H, O, P, and Br and the effective potential LANL2DZ[14]
basis set for Pd. All of the optimized structures were either characterized
by frequency calculations as energy minima without imaginary frequen-
cies or as transition states with only one imaginary frequency; the imagi-
nary model connected the initial and final states. At first, we used trime-
thylphosphine (PMe3) as the ligand and small substrates (CH3Br and
(E)-3-Benzylidene-5-(4-chlorophenyl)furan-2ACTHNUTRGNEUG(N 3H)-one:
1H NMR (300 MHz, CDCl3): d=7.51–7.66 (m, 4H), 7.31–7.44 (m, 6H),
6.85 ppm (d, J=0.98 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=169.1,
155.9, 136.5, 136.1, 135.1, 130.5, 130.2, 129.3, 129.2, 126.6, 125.2,
100.3 ppm; GCMS (EI, 70 eV): m/z (%): 282 (50) [M]+, 207 (35), 139
(100), 111 (30), 75 (10).
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CH3CH2C CH) to map the potential-energy surface, that is, to estimate
(E)-3-Benzylidene-5-(4-fluorophenyl)furan-2ACTHNUTRGNEUG(N 3H)-one:
the more-stable or the most-stable intermediates and the resting states.
On the basis of these results, under the consideration of the more- or
most-favorable potential-energy surface, we used the “real-sized” sub-
1H NMR (300 MHz, CDCl3): d=7.64–7.73 (m, 2H), 7.53–7.57 (m, 2H),
7.34–7.44 (m, 4H), 7.03–7.12 (m, 2H), 6.81 ppm (br s, 1H); 13C NMR
(75 MHz, CDCl3): d=167.5 (d, J=270.63 Hz), 156.0, 135.6, 135.1, 130.4,
130.1, 129.2, 127.5, 127.4, 125.3, 124.4 (d, J=3.82 Hz), 116.2 (d, J=
22.49 Hz), 99.5 ppm (d, J=2.33 Hz); GCMS (EI, 70 eV): m/z (%): 266
(65) [M]+, 207 (15), 123 (100), 95 (40).
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strates (PhBr and PhCH2C CH) for our calculations to estimate the dif-
ference between aliphatic and benzylic alkynes. We also used the real-
size tri-tert-butylphosphine (PtBu3), tricyclohexylphosphine (PCy3), triACTHNUGRTNEUNG(2-
furyl)phosphine (TFP, PFu3), and triphenylphosphine (PPh3) ligands to
calculate the barriers to the rate-determining step (Scheme 4). Because
the preferred reaction cycle does not directly involve PhBr or PhI
(Scheme 4), we used PhI as our starting substrate. For discussion and
comparison, we used the Gibbs free energies (DG) at 298 K (unless oth-
erwise noted). We also carried out self-consistent reaction-field (SCRF)
computations by using the polarizable continuum model (PCM[15]) with
water as a polar solvent to estimate the influence of the solvent on the
reaction energies. These results show that such a polar solvent does not
affect the barrier for the rate-determining step (less than 1 kcalmolÀ1).
The Gaussian 03 program package was used for all calculations.[16]
(E)-4-(4-Benzylidene-5-oxo-4,5-dihydrofuran-2-yl)benzonitrile:
1H NMR (300 MHz, CDCl3): d=7.77 (d, J=8.8 Hz, 2H), 7.66 (d, J=
8.8 Hz, 2H), 7.55–7.61 (m, 2H), 7.49 (br s, 1H), 7.39–7.44 (m, 3H),
7.02 ppm (d, J=1.0 Hz, 1H); GCMS (EI, 70 eV): m/z (%): 273 (80)
[M]+, 207 (10), 130 (100), 115 (15), 102 (20).
(E)-5-(4-Acetylphenyl)-3-benzylidenefuran-2ACTHNUTRGNEUG(N 3H)-one:
1H NMR (300 MHz, CDCl3): d=7.92–8.01 (m, 3H), 7.77 (d, J=8.7 Hz,
2H), 7.56–7.61 (d, 2H), 7.38–7.46 (m, 3H), 7.00 (d, J=1.1 Hz, 1H),
2.56 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): d=d 197.4, 169.1, 155.9,
138.0, 137.4, 135.0, 132.1, 130.8, 130.3, 129.3, 128.9, 125.5, 125.1, 102.3,
26.9 ppm; GCMS (EI, 70 eV): m/z (%): 290 (80) [M]+, 207 (70), 147
(100), 115 (10), 91 (10).
(E)-3-Benzylidene-5-phenylfuran-2ACTHNURGTNE(UNG 3H)-one:
1H NMR (300 MHz, CDCl3): d=7.75–7.81 (m, 2H), 7.62–7.67 (m, 2H),
7.42–7.52 (m, 7H), 6.95 ppm (d, J=0.98 Hz, 1H); 13C NMR (75 MHz,
CDCl3): d=169.3, 156.8, 135.4, 135.0, 130.4, 130.2, 130.0, 129.0, 128.8,
127.9, 125.3, 125.2, 99.8 ppm; GCMS (EI, 70 eV): m/z (%): 248 (60)
[M]+, 105 (100), 77 (25).
(E)-3-Benzylidene-5-(thiophen-3-yl)furan-2ACTHNUTRGNEUG(N 3H)-one:
1H NMR (300 MHz, CDCl3): d=7.64 (dd, J1 =2.63 Hz, J2 =1.52 Hz, 1H),
7.48–7.54 (m, 2H), 7.27–7.39 (m, 6H), 6.63 ppm (d, J=0.76 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=169.3, 153.3, 135.1, 135.0, 130.2, 130.1,
129.9, 129.0, 127.2, 125.1, 124.4, 99.4 ppm; GCMS (EI, 70 eV): m/z (%):
(E)-3-Benzylidene-5-p-tolylfuran-2ACTHNURGTNE(UNG 3H)-one:
1H NMR (300 MHz, CDCl3): d=7.45–7.58 (m, 4H), 7.23–7.39 (m, 4H),
7.12 (d, J=8.14 Hz, 2H), 6.74 (br s, 1H), 2.27 ppm (s, 3H); 13C NMR
(75 MHz, CDCl3): d=169.4, 157.0, 140.9, 135.1, 134.6, 130.0, 129.9, 129.5,
128.9, 125.4, 125.21, 125.18, 98.9, 21.5 ppm; GCMS (EI, 70 eV): m/z (%):
262 (70) [M]+, 119 (100), 91 (30), 65 (15).
254 (50) [M]+, 111
(E)-3-(3,4-Dimethoxybenzylidene)-5-phenylfuran-2ACTHGUNTRNE(NGU 3H)-one:
ACHTUNGTREN(NUNG 100), 83 (10).
1H NMR (300 MHz, CDCl3): d=7.56–7.66 (m, 2H), 7.26–7.37 (m, 3H),
7.21 (s, 1H), 7.15 (dd, J1 =8.55 Hz, J2 =2.06 Hz, 1H), 6.96 (d, J=1.90 Hz,
1H), 6.82 (d, J=8.28 Hz, 1H), 6.76 (d, J=0.80 Hz, 1H), 3.83 (s, 3H),
3.82 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): d=169.6, 155.9, 151.0,
149.1, 135.6, 130.1, 128.7, 128.0, 127.9, 125.1, 124.3, 122.9, 112.6, 111.3,
99.7, 55.9 ppm (br s); GCMS (EI, 70 eV): m/z (%): 308 (100) [M]+, 175
(50), 131 (10), 105 (90), 77 (40).
(E)-3-Benzylidene-5-(4-tert-butylphenyl)furan-2ACTHNUGRTNEUNG(3H)-one:
1H NMR (300 MHz, CDCl3): d=7.48–7.62 (m, 4H), 7.26–7.40 (m, 6H),
6.79 (d, J=0.96 Hz, 1H), 1.24 ppm (s, 9H); 13C NMR (75 MHz, CDCl3):
d=169.5, 157.1, 154.1, 135.2, 134.7, 130.1, 129.9, 129.0, 125.8, 125.4, 125.2,
Chem. Eur. J. 2012, 18, 16177 – 16185
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
16183