Palladium-Catalyzed Reductive Carbonylations
58(25), 56(17), 48(28); HRMS (EI, 70 eV) m/z: calcd for C23H37OP:
360.25765; found: 360.257829.
Ligand B
Sodium (276 mg, 12 mmol) was dissolved in n-propanol (20 mL) in
a 100 mL Schlenk tube under an atmosphere of argon. Then the solvent
was removed under high vacuum to afford a white solid. Diethyl ether
(30 mL) and (tBu)2PCl (1.52 mL, 8 mmol) were then added to the sus-
pension at room temperature. The reaction mixture was left overnight
and degassed water (20 mL) was added. The organic phase was separated
and dried over Na2SO4 under argon. By a cannula, the solution was fil-
tered under argon through a Celite pad and diethyl ether was removed
under vacuum. A colorless, clear, and pyrophoric liquid was obtained in
98% yield (1.61 g). 1H NMR (300.13 MHz, CDCl3): d=3.68 (q, J=
6,7 Hz, 3H, OCH2), 1.62 (sext, J=6.7 Hz, 2H, CH2), 1.08 (d, J=11.3 Hz,
18H, tBu), 0.93 ppm (t, J=7.5 Hz, 3H, CH3); 13C NMR (75.47 MHz,
CDCl3): d=75.4 (d, J=19.4 Hz, OCH2), 34.9 (d, J=23.2 Hz, C), 27,4 (d,
J=15.1 Hz, tBu), 24.8 (d, J=7.2 Hz, CH2), 10.5 ppm (CH3). 31P NMR
(121.5 MHz, CDCl3): d=159.6 ppm. MS (EI, 70 eV): m/z (%)=204 (24)
[M]+, 163 (23), 162 (15), 107 (59), 106 (35), 105(23), 87(42), 63(25), 57-
Scheme 2. In situ protocol 1 and 2.
was achieved with the in situ protocol 2. The former proto-
col is more efficient because (tBu)2PCl and n-propanol
blend better in this case and ligand B is formed more easily
than if solid sodium propanolate is used. In situ preparation
of ligands is a strong tool for optimizing a model reaction.
To improve the conversion of mesitylbromide to mesitylal-
dehyde (Table 2, entry 5), we screened different solvents
such as MeOH, EtOH, BuOH, and iPrOH using in situ pro-
tocol 1. Unfortunately, the yield was in the range of 3–6%
and 5–10% for conversion. These results emphasize that the
topology of the ligand is very important in the reductive car-
bonylation.
In conclusion, we have developed efficient phosphinite li-
gands for the palladium-catalyzed reductive carbonylation
of aryl bromides to aromatic aldehydes. Several aryl bro-
mides with electron-donating and electron-withdrawing sub-
stituents reacted to give aldehydes in good to excellent
yields. Additionally, the reductive carbonylation can be car-
ried out using in situ prepared propyl di-tert-butylphosphin-
ite (ligand B), which is synthesized by a treating commer-
cially available (tBu)2PCl with n-propanol in the presence of
TMEDA. As (tBu)2PCl is significantly cheaper than
BuPAd2, this new synthetic methodology is a valuable alter-
native to the established synthesis of BuPAd2.
AHCUTNERTGGUN(NN 100). HRMS (ESI) m/z: calcd for C11H26OP: 205.17158; found:
205.17182.
Ligand C
THF (13 mL), n-propylamine (1.48 mL, 18 mmol), and triethylamine
(1.66 mL, 12 mmol) were added under argon to a 50 mL Schlenk flask
equipped with a stirring bar and septum. After cooling the reaction mix-
ture to 08C with an ice bath, (tBu)2PCl (1.5 mL, 7.9 mmol) was slowly
added and a white solid precipitated. The reaction solution was stirred
for 1.5 days at room temperature. The white precipitate was allowed to
settle and through a cannula the solution was filtrated and the solid was
extracted with THF (3ꢄ5 mL). The solvent and the excess amine were
removed under high vacuum and a cloudy liquid remained, which was di-
luted with diethyl ether (7 mL). After filtering the solution over Celite,
a clear liquid was obtained. The solvent was removed under vacuum, and
a clear, pyrophoric liquid was obtained in 73% yield (1.5 g). 1H NMR
(300.13 MHz, CDCl3): d=2.94–2.83 (m, 2H, NCH2), 1.46 (sext, J=
7.2 Hz, 2H, CH2), 1.04 (d, J=11.3 Hz, 18H, tBu), 0.68 ppm (t, J=7.2 Hz,
3H, CH3). 13C NMR (75.47 MHz, CDCl3): d=52.5 (d, J=26.9 Hz,
NCH2), 33.8 (d, J=18.8 Hz, C), 28,2 (d, J=14.5 Hz, tBu), 26.4 ppm (d,
J=6.6 Hz, CH2), d=11.4 ppm (CH3). 31P NMR (121.5 MHz, CDCl3): d=
78.3 ppm. MS (EI, 70 eV): m/z (%)=203 (12) [M]+, 146 (31), 90 (100),
57 (8). HRMS (ESI) m/z: calcd for C11H27NP: 204.18756; found:
204.18794.
Reaction procedure for the reductive carbonylation
A stock solution was prepared, in which each 2 mL contains PdACHTUNGTRENNUNG(OAc)2
Experimental Section
(1.10 mg, 0.5 mol%) and ligand B (3.10 mg, 1.5 mol%). A 2 mL stock so-
lution was added under an argon atmosphere to each of the six vials
(4 mL reaction volume) placed in an alloy plate, equipped with a septum,
cannula, and stirring bar. After adding TMEDA (113.2 mL, 0.75 mmol,
0.75 equiv), aryl bromide (1 mmol), and hexadecane (60 mL) to the vials,
the alloy plate was transferred into a 300 mL autoclave (Parr Instru-
ments, 4560 series) under an argon atmosphere. After flushing the auto-
clave three times with CO/H2 and then pressurized to 5 bar CO/H2, the
reaction was performed for 20 h at 1008C. When the reaction was finish-
ed the autoclave was cooled down to room temperature, CO/H2 was re-
leased and a sample was analyzed by GC to determine the yield and con-
version.
Ligand A
Sodium (43.7 mg, 1.9 mmol) was added to absolute n-propanol (20 mL)
in a 100 mL Schlenk tube. When the sodium was dissolved, Ad2PCl
(500 mg, 1.48 mmol) was added in portions. Then, the mixture was
heated to 908C for 1 hour. After the n-propanol was removed under
vacuum, water (15 mL) and CH2Cl2 (20 mL) were added to the residual
white solid. The phases were separated and the organic phase was dried
over Na2SO4. When the solvent was removed, a white solid (560 mg) was
obtained. For further purification, the solid was dissolved in CH2Cl2
(5 mL) and MeOH (20 mL). Keeping the solution in the refrigerator
overnight afforded a white solid, which is stable to air over a few weeks.
31% yield (165 mg); 1H NMR (300.13 MHz, CDCl3): d=3.62 (q, J=
7,1 Hz, 3H, OCH2), 1.97–1.90 (m, 6H, CH), 1.90–1.84 (m, 12H, CH2)
1.75–1.69 (m, 12H, CH2), 1.63 (sext, J=7.3 Hz, 2H, CH2), 0.93 ppm (t,
J=7.3 Hz, 3H, CH3); 13C NMR (75.47 MHz, CDCl3): d=76.1 (d, J=
19.2 Hz, OCH2), 39.3 (d, J=23.6 Hz, C), 38.6 (d, J=12.6 Hz, CH2), 28.4
(d, J=8.2 Hz, CH), 37.2 (CH2), 24.7 (d, J=6.8 Hz, CH2), 10.5 ppm
(CH3); 31P NMR (121.5 MHz, CDCl3): d=157.9 ppm; MS (EI, 70 eV): m/
z (%)=360 (0.84) [M]+, 169 (19), 135 (100), 93 (19), 91(16), 60(14),
In situ protocol 1
Toluene (4 mL), TMEDA (565.9 mL, 3.75 mmol, 0.75 equiv), (tBu)2ClP
(14.2 mL, 1.5 mol%), and n-propanol (1.5 mol%) were added to a 12 mL
vial equipped with a stirring bar, septum, and small cannula under an
argon atmosphere. After the solution was stirred for 10 min, bromoben-
zene (523.4 mL, 5 mmol), PdACHTNUGTRNEUNG(OAc)2 (5.6 mg, 0.5 mol%), and hexadecane
(300 mL) were added. The vial was placed in an alloy plate, which was
transferred into a 300 mL autoclave (Parr Instruments, 4560 series) under
Chem. Asian J. 2012, 00, 0 – 0
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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