Synthesis of 3-Substituted Furans by Hydroformylation
FULL PAPERS
(1:1) at 60 8C for 24 h in CH2Cl2 gave very low product Table 2. Effect of the ligand on the hydroformylation of 3-
phenyl-2-propyn-1-ol.[a]
yields (<10%). Other catalysts, such as Pd(OAc)2,
PdCl2,
PdCl2(PhCN)2,
Pd(PCy3)2,
Pd(PPh3)4,
(CH3CN)4Pd(BF4)2 and [Rh(COD)Cl]2, did not form
the furan, and only the starting material was recovered.
The influence of the ratio of CO/H2 was evaluated by
using the [Rh(OAc)2]2/PPh3 catalyst system in CH2Cl2 at
608C. It was found that the optimum CO/H2 pressure for
the hydroformylation reaction was 350/350 psi. The for-
mation of hydrogenated by-products, instead of the hy-
droformylated product, was favoured at low CO and
high H2 pressure.
The presence of a phosphine ligand was essential for
the reaction catalyzed by [Rh(OAc)2]2, as no conversion
of aryl-substituted propargylic alcohol occurred in the
absence of triphenylphosphine. To investigate the effect
of the added phosphine ligand on the reaction, various
types of phosphine ligands were employed when 3-phe-
nyl-2-propyn-1-ol was used as the reactant, and the re-
sults are summarized in Table 2. Different bidentate li-
Entry
Ligand
Yield of 2 [%][b]
1PPh
65
15
18
–
3
2
3
4
dppp
dppb
P(OPh)3
[a]
Reaction conditions: [Rh(OAc)2]2 (0.02 mmol), ligand
(0.08 mmol), phenylpropargylic alcohol (1mmol), 2.5 mL
of solvent, 700 psi CO/H2 (1: 1), 65 8C, 24 h.
GC yield.
[b]
gands were employed for the hydroformylation reac- Table 3. Effect of the solvent on the hydroformylation of 3-
phenyl-2-propyn-1-ol.[a]
tion. 1,3-Bis(diphenylphosphino)propane (dppp) and
1,4-bis(diphenylphosphino)butane (dppb) were less ef-
fective than PPh3, giving 15% and 18% yields, respec-
tively (entries 2 and 3). Pruett and Smith reported that
phosphites are more effective than phosphines for the
hydroformylation of allylic alcohols.[19] However, the
use of triphenyl phosphite [P(OPh)3] in our system did
not afford the hydroformylated product (entry 4).
Entry
Solvent
Yield of 2 [%][b]
From these experiments, we concluded that PPh3 was
the ligand of choice for our catalytic system (entry 1).
The influence of the solvent on the yield of the hydro-
formylation reaction was also studied, using different
anhydrous solvents. The results of the solvent study
are summarized in Table 3. Using rhodium acetate-tri-
phenylphosphine as the catalyst system, we found that
the reaction occurred giving good product yields when
CH2Cl2 is the solvent (entry 3). Other solvents, such as
toluene, benzene or ether afforded somewhat lower
yields compared to CH2Cl2 (entries 1, 2 and 4).
1Toluene
57
Benzene
CH2Cl2
Et2O
2
3
4
49
65
43
[a]
Reaction conditions: [Rh(OAc)2]2 (0.02 mmol), PPh3
(0.08 mmol), phenylpropargylic alcohol (1mmol), 2.5 mL
of solvent, 700 psi CO/H2 (1: 1), 65 8C, 24 h.
GC yield.
[b]
The effect of temperature was next investigated by
The maximum yield of the hydroformylated product
employing 3-phenyl-2-propyn-1-ol in the presence of was obtained when 5/20 mol % of [Rh(OAc)2]2/PPh3
[Rh(OAc)2]2/PPh3 in CH2Cl2, and the results are sum- was used (entry 3), and below that the yields were some-
marized in Table 4.
what lower (entries 1and 2). Clearly, the number of
The optimum temperature suitable for the hydrofor- phosphines coordinated to rhodium determines the re-
mylation reaction was found to be 65–708C. When the gioselectivity. At high PPh3 concentration, rather low
reaction was performed at 1008C, the yield of hydrofor- product yield was obtained (entry 4). This could be
mylated product was much lower (entry 3) and lower re- due to the high ligand concentration which competes
gioselectivity and chemoselectivity were observed. with the substrate for binding to the active rhodium spe-
Among other side reactions, hydrogenation of the sub- cies.
strate, and condensation reactions are the most impor-
We propose that the water, which is eliminated during
the reaction, could be captured by adding molecular
tant.[20]
The conversion and the formation of by-products are sieves to the reaction mixture. Hence, the addition of
also found to be controlled by the catalyst concentra- 0.1g of 4 molecular sieves to each reaction mixture
tion. Besides the temperature and the reaction time, of phenylpropargylic alcohol in the presence of 700 psi
the catalyst feed is the third parameter to influence the CO/H2 (1:1), at 60 8C for 24 h in CH2Cl2 increased the
conversion (Table 5).
yield of product 2 from 38% to 47%.
Adv. Synth. Catal. 2006, 348, 545 – 550
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
547