The iridium-catalyzed decarbonylation of aldehydes under mild conditions

Article abstract of DOI:10.1039/b813171f

The catalytic decarbonylation of aldehydes has been developed using commercially available [IrCl(cod)]₂ and PPh₃ under mild conditions, and the method could be widely applicable to various substrates with different functionalities. The Royal Society of Chemistry.

Full text of DOI:10.1039/b813171f

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The iridium-catalyzed decarbonylation of aldehydes under mild
conditionsw
Tomohiro Iwai, Tetsuaki Fujihara and Yasushi Tsuji*
Received (in Cambridge, UK) 1st August 2008, Accepted 1st October 2008
First published as an Advance Article on the web 29th October 2008
DOI: 10.1039/b813171f
The catalytic decarbonylation of aldehydes has been developed
using commercially available [IrCl(cod)]2 and PPh3 under mild
conditions, and the method could be widely applicable to various
substrates with different functionalities.
PPh3 or P(n-Bu)3, provides a highly active and practical
catalyst system.
cat: ½IrClðcodÞ2ꢁ-PR0
3
RꢀCHO
R ꢀ H þ CO "
ð1Þ
ƒƒƒƒƒƒƒƒƒƒƒƒƒ!
at 66 ꢂCꢀ101 ꢂ
C
The removal of formyl functionalities, the decarbonylation of
aldehydes, is one of the essential protocols of synthetic chem-
istry, including in the total syntheses of natural products.1 The
decarbonylation reaction of aldehydes was first discovered by
Tsuji and Ohno using a stoichiometric amount of Wilkinson’s
complex, RhCl(PPh3)3.2 As for catalytic reactions, Doughty
and Pignolet found that rhodium complexes with chelating
diphosphines were much more reactive as catalysts.3 Since then,
rhodium catalysts with chelating phosphines have been exten-
sively studied in decarbonylation reactions of aldehydes.4
Recently, Madsen and co-workers reported a mechanism for
the rhodium-catalyzed decarbonylation of aldehydes by DFT
calculations.5a They mentioned that the reaction involves a
rapid oxidative addition into the C(O)–H bond, followed by a
rate-limiting extrusion of CO. Some Pd6 and Ru,7 as well as
Ir,8 complexes were also reported as catalysts for decarbonyla-
tion and related reactions.
Firstly, the decarbonylation of 2-naphthaldehyde was carried
out to examine the effect of the catalyst system (Table 1). In the
presence of a catalytic amount of [IrCl(cod)]2 (5.0 mol% with
respect to Ir) and PPh3 (PPh3 : Ir = 1 : 1) in refluxing diglyme (bp
162 1C), the decarbonylation product, naphthalene, was obtained
in 92% yield (Table 1, entry 1). The best decarbonylation catalyst
reported so far, RhCl3ꢃ3H2O with dppp (1,3-bis(diphenylphos-
phino)propane),4b also afforded the product in a high yield in
refluxing diglyme (Table 1, entry 2). However, the catalytic
activity dropped drastically when the reaction was carried out
in refluxing dioxane (bp 101 1C) (Table 1, entry 3). Thus, the
elevated temperature is a requisite for rhodium catalysts. In
contrast, the [IrCl(cod)]2–PPh3 catalyst system showed a high
catalytic activity, even in refluxing dioxane, and gave the product
in 79% yield in 24 h and in 95% yield in 48 h (Table 1, entries 4
and 5). As catalyst precursors, IrCl3ꢃ3H2O, [Ir(cod)2]BF4 and
[IrCl2Cp*]2 (Cp* = Z5-pentamethylcyclopentadienyl) gave the
However, in order to realize the efficient catalytic (or even
stoichiometric) decarbonylation of aldehydes, elevated reac-
tion temperatures (typically 4160 1C)1a,b,g,3,4a,b,d,5a,6 or an
associated chemical scavenger of the evolved CO (i.e., by an
accompanying carbonylation reaction4c,8,9 or with added di-
phenylphosphoryl azide10 to remove the evolved CO) are
indispensable. Actually, more than a stoichiometric, not a
catalytic, amount of RhCl(PPh3)3 is still being used to obtain
efficient decarbonylations of aldehyde functionalities as an
important step in various total syntheses.1a–g Hence, a much
more active catalyst system to realize the reliable catalytic
decarbonylation of aldehydes at lower temperatures, and
without a chemical scavenger for CO, is highly desirable.
In the present study, we describe a highly active iridium
catalyst system that realizes the efficient catalytic decarbonyla-
tion of aldehydes at lower temperatures (66 1C–101 1C) and
without any chemical scavenger of CO (eqn (1)). A simple
combination of commercially available [IrCl(cod)]2 (cod =
1,5-cyclooctadiene) and an easily accessible phosphine, such as
Table 1 The iridium-catalyzed decarbonylation of 2-naphthaldehyde:
effect of catalyst precursors, ligands and solventsa
Entry [M]
Ligand
Solvent Time/h Yield (%)b
1
2
3
4
5
6
7
8
[IrCl(cod)]2
PPh3
RhCl3ꢃ3H2O dpppc
RhCl3ꢃ3H2O dpppc
Diglyme
6
92
90
Diglyme 24
Dioxane 24
Dioxane 24
Dioxane 48
Dioxane 24
Dioxane 24
Dioxane 24
Dioxane 24
Dioxane 24
Dioxane 24
Dioxane 24
1
79
[IrCl(cod)]2
[IrCl(cod)]2
IrCl3ꢃ3H2O
PPh3
PPh3
PPh3
95 (87d)
2
14
[Ir(cod)2]BF4 PPh3
[IrCl2Cp*]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
PPh3
3
9
P(n-Bu)3
PCy3
dppe
95 (81d)
10
11
12
13
14
15
16
89 (82d)
28
7
49
84
31
86
dppp
(ꢄ)-BINAP Dioxane 24
P(n-Bu)3
PPh3
PPh3
DME
DME
Toluene 24
48
48
Department of Energy and Hydrocarbon Chemistry, Graduate School
of Engineering, Kyoto University, Kyoto 615-8510, Japan.
E-mail: ytsuji@scl.kyoto-u.ac.jp
w Electronic supplementary information (ESI) available: Experimental
procedures and measurement of the kinetic isotope effect. See DOI:
10.1039/b813171f
a
Reaction conditions: 2-naphthaldehyde (0.50 mmol), [M] (0.025 mmol
with respect to Ir or Rh), ligand (0.025 mmol), solvent (1.0 cm3),
b
c
d
reflux, Ar atmosphere. GC yields. dppp (0.050 mmol). In air with
unpuirifed dioxane.
ꢅc
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Chem. Commun., 2008, 6215–6217 | 6215

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product in only low yields (Table 1, entries 6–8). The phosphines
P(n-Bu)3 and tricyclohexylphosphine (PCy3), of higher basicity,
were more efficient and afforded the product in 95 and 89%
yields, respectively (Table 1, entries 9 and 10, cf. entry 4), in 24 h.
Although bidentate phosphines such as dppe (1,2-bis(diphenyl-
phosphino)ethane), dppp and (ꢄ)-BINAP (2,20-bis(diphenylphos-
phino)-1,10-binaphthyl) were found to be noticeably effective
in the Rh catalyst system,4b–d they were not as efficient as PPh3
with the iridium catalyst (Table 1, entries 11–13). These results
suggest that the use of a monodentate phosphine is more
favorable in iridium-catalyzed decarbonylation reactions.
However, with excess PPh3 (PPh3 : Ir = 2 : 1), the yield
decreased to 4% under otherwise identical conditions to those
in Table 1, entry 4. Furthermore, the iridium catalyst system
with P(n-Bu)3 showed a good catalytic activity, even in
refluxing 1,2-dimethoxyethane (DME, bp 85 1C) (Table 1,
entry 14), although PPh3 was not such an efficient ligand in
DME (Table 1, entry 15). Hydrocarbon solvents, such as
toluene, can also be employed in this reaction, as shown in
Table 1, entry 16. It is noteworthy that this decarbonylation
reaction can be carried out in unpurified (as received) dioxane
and in air, albeit with slightly decreased yields (Table 1, entries
5, 9 and 10).
electron-rich (Table 2, entries 1 and 2) and electron-poor
(Table 2, entries 3–6) aldehydes provided the corresponding
products in good-to-high yields. In the RhCl3ꢃ3H2O–dppp-
catalyzed decarbonylation reaction in refluxing diglyme, para-
nitrobenzaldehyde was reported to be partially decomposed
and afforded the decarbonylation product in only 12% yield.4b
However, with the iridium catalyst, the decarbonylation could
be carried out smoothly in refluxing dioxane, and the product
was isolated in 87% yield (Table 2, entry 5). Sterically
hindered 2,4,6-trimethoxybenzaldehyde was smoothly decar-
bonylated (Table 2, entry 7). While, the decarbonylation of
salicylaldehyde did not proceed, possibly due to intramolecu-
lar coordination of the OH functionality, meta-hydroxybenz-
aldehyde provided the decarbonylation product in an excellent
yield (Table 2, entry 8). 5-Phenylthiophene-2-carboxyaldehyde
gave 2-phenylthiophene in 94% yield (Table 2, entry 9),
and the decarbonylation of para-amyloxybenzaldehyde-d1
afforded the product bearing the deuterium at the para-position
in 81% yield (Table 2, entry 10).
Table 3 The iridium-catalyzed decarbonylation of various aldehydesa
The decarbonylation of aromatic aldehydes was carried out
in refluxing unpurifed dioxane under air (Table 2).z Both
½IrClðcodÞ2ꢁ-phosphine
solvent; reflux; air
RꢀCHO
RꢀH þ CO "
ƒƒƒƒƒƒƒƒƒƒƒƒƒ!
Yield
(%)b
Entry Aldehyde
Solvent
Time/h Product
Table 2 The iridium-catalyzed decarbonylation of aromatic aldehydesa
1
2
3
4
5
6
Dioxane
Dioxane 32
9
84 (99)
(94)cd
(79)c
(91)ce
(82)ce
92
½IrClðcodÞ2ꢁ-PPh3
dioxane; reflux; air; 48 h
ArꢀCHO
ArꢀH þ CO "
ƒƒƒƒƒƒƒƒƒƒƒƒƒ!
DME
DME
THF
24
24
96
Entry Aldehyde
Product
Yield (%)b
91
Dioxane 24
1
2
3
4
5
6
76
79
84
87
91
7
8
Dioxane 24
Dioxane 24
82
63f
9
Dioxane 24
Dioxane 24
91g
72h
10
11
Dioxane 24
Dioxane 24
81i
3j
7
78
12
8
9
95c
a
Reaction conditions: aldehyde (1.0 mmol), [IrCl(cod)]2 (0.025 mmol),
PPh3 (0.050 mmol), refluxing dioxane (unpurified, 1.0 cm3) for 24 h in
94
b
air. Isolated yields. Under argon. [IrCl(cod)]2 (0.0025 mmol), PPh3
c
d
e
f
g
(0.0050 mmol). With PCy3 in place of PPh3. E : Z = 16 : 84. In
10
81d
h
addition, nonenes were obtained in 5% yield. In addition, styrene was
i
obtained in 6% yield. In addition, styrene was obtained in 10%
a
Reaction conditions: aldehyde (1.0 mmol), [IrCl(cod)]2 (0.025 mmol),
PPh3 (0.050 mmol), refluxing dioxane (unpurified, 1.0 cm3) for 48 h in
j
yield. In addition, 1-isopropenyl-4-methylbenzene was obtained in
6% yield.
b
air. Isolated yields. GC yield. For 72 h.
c
d
ꢅc
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Table 3 shows the results of the decarbonylation of various
aldehydes. The decarbonylation of a,b-unsaturated aldehydes
proceeded somewhat more rapidly. trans-Cinnamaldehyde
provided styrene in 99% yield in 9 h (Table 3, entry 1). The
product was obtained in high yield, even if the catalyst loading
was reduced to one tenth of the standard amount (Table 3,
entry 2). In DME under reflux, styrene was obtained in 79%
yield (Table 3, entry 3). When PCy3 was used in place of PPh3
in DME, the yield increased to 91% yield (Table 3, entry 4).
Surprisingly, with the [IrCl(cod)]2–PCy3 catalyst system, the
decarbonylation of trans-cinnamaldehyde proceeded in high
yield, even in refluxing THF (bp 66 1C) (Table 3, entry 5). The
corresponding decarbonylation products were isolated in high
yields from citral (Table 3, entry 6) and (S)-perillaldehyde
(Table 3, entry 7). (E)-2-Methyl-3-phenyl-2-propenal afforded
the decarbonylation product in 63% yield in 24 h with E/Z
isomerization to E : Z = 16 : 84 (Table 3, entry 8). In this case,
by prolonging the reaction time to 48 h, the yield of b-
methylstyrenes increased to 90%, but the isomerization pro-
ceeded further to E : Z = 93 : 7. In the case of aldehydes
having b-hydrogens on an sp3 carbon, the decarbonylation
reaction proceeded smoothly, but alkenes formed simulta-
neously in 5–10% yields due to b-hydrogen elimination
(Table 3, entries 9–11). As for limitations, the conversion of
an a,a-dialkylated aldehyde was very low in the present
catalyst system (Table 3, entry 12), as seen in previous
rhodium catalyzed reactions.4b
thank Professor Jun Terao at Kyoto University for helpful
discussions.
Notes and references
z General procedure for the decarbonylation of aldehydes (Table 2,
entry 1): A solution of [IrCl(cod)]2 (16.8 mg, 0.025 mmol) and PPh3
(13.1 mg, 0.050 mmol) in dioxane (unpurified, 1.0 cm3) was stirred at
room temperature for 10 min in air. para-Dimethylaminobenzalde-
hyde (149 mg, 1.0 mmol) was added to the flask and the reaction
carried out under reflux for 48 h. After cooling to room temperature,
the mixture was diluted with pentane, and washed with water and
brine. The organic layer was dried over Na2SO4, filtered and evapo-
rated carefully. The crude product was purified by silica gel column
chromatography using pentane–CH2Cl2 (5 : 1) as an eluent to give
N,N-dimethylaniline (110 mg, 91%) as a colorless oil.
1 (a) A. Padwa and H. Zhang, J. Org. Chem., 2007, 72, 2570–2582;
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To examine the reaction mechanism of the iridium-catalyzed
decarbonylation of aldehydes, we measured the kinetic isotope
effect. The rate of the iridium-catalyzed decarbonylation reac-
tion has a first-order dependence on aldehyde concentration.
Kinetic measurements with para-amyloxybenzaldehyde-d1
(Table 2, entry 10) vs. para-methoxybenzaldehyde and a com-
parison of the kD value with the kH value for para-amyloxy-
benzaldehyde-d0 afforded a deuterium isotope effect kH/kD
=
1.70. This value is comparable to kH/kD = 1.775a and 1.85b
reported previously for rhodium-catalyzed decarbonylations.
In conclusion, the iridium-catalyzed decarbonylation of
aldehydes using a catalytic amount of commercially available
[IrCl(cod)]2 and an easily accessible monodentate phosphine
such as PPh3 or P(n-Bu)3 was developed. The reaction pro-
ceeded smoothly under mild reaction conditions. This highly
practical and reliable method should be widely applicable to
various substrates containing different functionalities.
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This work was supported by a Grant-in-Aid for Scientific
Research on Priority Areas from the Ministry of Education,
Culture, Sports, Science and Technology, Japan. T. I. is
grateful for a Research Fellowship from the Japan Society
for the Promotion of Science (JSPS) for Young Scientists. We
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ꢅc
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Chem. Commun., 2008, 6215–6217 | 6217