Iridium-catalyzed transfer hydrogenation of α,β-unsaturated and saturated carbonyl compounds with 2-propanol

Article abstract of DOI:10.1021/jo0156722

The selective transfer hydrogenation of α,β-unsaturated carbonyl compounds to saturated ones was achieved by the use of 2-propanol as a hydrogen donor under the influence of catalytic amounts of [Ir(cod)Cl]₂, 1,3-bis(disphenylphosphino)propane (dppp), and Cs₂CO₃. Thus, a variety of conjugated enones were allowed to react with 2-propanol in the presence of the [Ir(cod)Cl]₂/dppp/Cs₂CO₃ system to give the corresponding saturated carbonyl compounds in good to excellent yields without formation of allylic alcohols. Both dppp and Cs₂CO₃ were essential components to achieve the reduction satisfactorily. Additionally, the reduction of carbonyl compounds to alcohols was also promoted by the same catalytic system. When the reaction of a 1:1 mixture of a conjugated ketone and a saturated ketone with 2-propanol was carried out in the presence of [Ir(cod)Cl]₂ combined with dppp and Cs₂CO₃, the reduction of the α,β-unsaturated ketone was found to take place in preference to that of the saturated ketone.

Full text of DOI:10.1021/jo0156722

4710
J . Org. Chem. 2001, 66, 4710-4712
Ir id iu m -Ca ta lyzed Tr a n sfer Hyd r ogen a tion of r,â-Un sa tu r a ted a n d
Sa tu r a ted Ca r bon yl Com p ou n d s w ith 2-P r op a n ol
Satoshi Sakaguchi, Takumi Yamaga, and Yasutaka Ishii*
Department of Applied Chemistry, Faculty of Engineering & High Technology Research Center,
Kansai University, Suita, Osaka 564-8680, J apan
ishii@ipcku.kansai-u.ac.jp
Received April 6, 2001
The selective transfer hydrogenation of R,â-unsaturated carbonyl compounds to saturated ones
was achieved by the use of 2-propanol as a hydrogen donor under the influence of catalytic amounts
of [Ir(cod)Cl]2, 1,3-bis(diphenylphosphino)propane (dppp), and Cs2CO3. Thus, a variety of conjugated
enones were allowed to react with 2-propanol in the presence of the [Ir(cod)Cl]2/dppp/Cs2CO3 system
to give the corresponding saturated carbonyl compounds in good to excellent yields without formation
of allylic alcohols. Both dppp and Cs2CO3 were essential components to achieve the reduction
satisfactorily. Additionally, the reduction of carbonyl compounds to alcohols was also promoted by
the same catalytic system. When the reaction of a 1:1 mixture of a conjugated ketone and a saturated
ketone with 2-propanol was carried out in the presence of [Ir(cod)Cl]2 combined with dppp and
Cs2CO3, the reduction of the R,â-unsaturated ketone was found to take place in preference to that
of the saturated ketone.
Ta ble 1. Tr a n sfer Hyd r ogen a tion of
In tr od u ction
4-P h en yl-3-bu ten -2-on e (1) to 4-P h en ylbu ta n -2-on e (2)
Chemoselective reduction of R,â-unsaturated carbonyl
compounds using an alcohol as a hydrogen source has
been widely studied, since the reaction is easily carried
out under mild conditions using an environmentally
benign and safe reagent like 2-propanol. The selective
reduction of the carbonyl group of R,â-unsaturated
compounds to allylic alcohols has been achieved with
relative ease.1,2 In contrast, the transfer hydrogenation
of the alkenic double bond of conjugated enones is
limited.3 The transfer hydrogenation of conjugated enones
with an alcohol is performed by the use of ruthenium1a-c,4
or rhodium5 complexes as catalyst, but the reduction
using iridium complexes is rare.2 Here, we wish to report
the Ir complex-catalyzed selective transfer hydrogenation
of R,â-unsaturated carbonyl compounds to saturated ones
and the reduction of carbonyl compounds using 2-pro-
panol as a hydrogen donor.
Ca ta lyzed by [Ir (cod )Cl]2 u n d er Selected Con d ition sa
entry
phosphine
base
convn (%)
yield (%)
1b
2b
3
4
5
6
7
8
9
PCy3
PPh3
dppe
dppp
dppb
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
76
99
89
93
93
2
31
42
58
25
58
37c
88
93
87
1
20
35
52
20
dppp
Cs2CO3
Na2CO3
Et3N
dppp
dppp
10
a
Compound 1 (0.5 mmol) was allowed to react with 2-propanol
(5 mmol) in the presence of a catalytic amount of [Ir(cod)Cl]2 (2
mol %), phosphine (2 mol %), and base (2 mol %) in toluene (0.5
mL) at 80 °C for 4 h. Phosphine (4 mol %) was used. c 4-Phenyl-
b
2-butanol (60%) was also obtained.
through double-bond migration followed by the Claisen
rearrangement by the use of a system consisting of [Ir-
(cod)Cl]2/PCy3/Cs2CO3.6 In the course of the study on the
behavior of the catalyst, we have found that the [Ir(cod)-
Cl]2/phosphine/Cs2CO3 system serves as an efficient
catalyst for the reduction of R,â-unsaturated carbonyl
compounds as well as carbonyl compounds using 2-pro-
panol as a hydrogen source.
Previously, we have shown the conversion of allyl
homoallyl ethers to γ,δ-unsaturated carbonyl compounds
(1) (a) Mizugaki, T.; Kanayama, Y.; Ebitani, K.; Kaneda, K. J . Org.
Chem. 1998, 63, 2378. (b) Bianchini, C.; Peruzzini, M.; Farnetti, E.;
Kasˇper, J .; Graziani, M. J . Organomet. Chem. 1995, 488, 91. (c)
Bhaduri, S.; Sharma, K. J . Chem. Soc., Chem. Commun. 1988, 173.
(d) Yoshinaga, K.; Kito, T.; Ohkubo, K. Bull. Chem. Soc. J pn. 1983,
56, 1786.
(2) (a) Zassinovich, G.; Mestroni, G. Chem. Rev. 1992, 92, 1051. (b)
Bianchini, C.; Farnetti, E.; Graziani, M.; Nardin, G.; Vacca, A.;
Zanobini, F. J . Am. Chem. Soc. 1990, 112, 9190. (c) De Martin, S.;
Zassinovich, G.; Mestroni, G. Inorg. Chim. Acta 1990, 174, 9. (d) J ames,
B. B.; Morris, H. R. J . Chem. Soc., Chem. Commun. 1978, 929.
(3) (a) Comprehensive Organic Synthesis; Trost, B. W., Ed.; Perga-
mon Press: Oxford, 1991; Vol. 8, pp 551-553 and references cited
therein. (b) Saburi, M.; Ohnuki, M.; Ogasawara, M.; Takahashi, T.;
Uchida, Y. Tetrahedron Lett. 1992, 33, 5783. (c) Sasson, Y.; Blum, J .
J . Org. Chem. 1975, 40, 1887. (d) Sasson, Y. Cohen, M.; Blum, J .
Synthesis 1973, 359. (e) Sasson, Y.; Blum, J . Tetrahedron Lett. 1971,
2167.
Resu lts
Table 1 shows the representative results for the
transfer hydrogenation of 4-phenyl-3-buten-2-one (1) with
2-propanol under selected conditions (eq 1). Treatment
of 1 with 2-propanol under the influence of catalytic
amounts of [Ir(cod)Cl]2, PCy3, and Cs2CO3 at 80 °C for 4
h gave 4-phenylbutan-2-one (2) in 58% yield (Table 1,
entry 1). The reaction was found to be considerably
(4) Bhaduri, S.; Sharma, K.; Mukesh, D. J . Org. Soc., Dalton Trans.
1992, 1, 77.
(5) (a) Beaupere, D.; Bauer, P.; Nadjo, L.; Uzan, R. J . Organomet.
Chem. 1982, 238, C12. (b) Beaupere, D.; Nadjo, L.; Uzan, R.; Bauer,
P. J . Mol. Catal. 1983, 18, 73.
(6) Higashino, T.; Sakaguchi, S.; Ishii, Y. Org. Lett. 2000, 2, 4193.
10.1021/jo0156722 CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/06/2001

Ir-Catalyzed Transfer Hydrogenation of Carbonyl Compounds
J . Org. Chem., Vol. 66, No. 13, 2001 4711
Ta ble 2. Tr a n sfer Hyd r ogen a tion of Va r iou s
influenced by the phosphine ligand used. When PPh3 was
added in place of PCy3, 1 was reduced to give 4-phenyl-
r,â-Un sa tu r a ted Ca r bon yl Com p ou n d s Ca ta lyzed by
a
[Ir (cod )Cl]2
2-butanol (60%) as a major product along with 2 (37%)
(Table 1, entry 2). It is noteworthy that the use of
bidentate phosphine ligands such as 1,3-bis(diphenylphos-
phino)ethane (dppe) and 1,3-bis(diphenylphosphino)pro-
pane (dppp) led to the selective formation of 2. In
particular, 2 was obtained with complete selectivity when
the reaction was carried out by the use of dppp as the
ligand (Table 1, entry 4). Thus, the selective transfer
hydrogenation of R,â-unsaturated ketone 1 to saturated
one 2 was successfully achieved by the use of an iridium
catalyst. Although almost no reaction took place when
[Ir(cod)Cl]2 complex was used alone, the reduction pro-
ceeded to some extent by the use of [Ir(cod)Cl]2 combined
with dppp or Cs2CO3 (Table 1, entries 6-8). The use of
Na2CO3 or Et3N as base resulted in low yield of 2 (Table
1, entries 9 and 10).
Table 2 summarizes the results for the transfer hy-
drogenation of various R,â-unsaturated carbonyl com-
pounds using the [Ir(cod)Cl]2/dppp/Cs2CO3 system. A
variety of R,â-unsaturated ketones were reduced to the
corresponding ketones in excellent yields except for
3-methyl-2-cyclohexen-1-one, which was reduced to the
corresponding alcohol with both carbon-carbon and
carbon-oxygen double bonds reduced (Table 2, entries
1-8). 2-Hexenal under these reaction conditions afforded
hexanal in 70% selectivity and hexanol (7%) at 75%
conversion (Table 2, entry 9).
The present [Ir(cod)Cl]2/dppp/Cs2CO3 system was also
found to promote the transfer hydrogenation of carbonyl
compounds and simple alkenes (Table 3). For instance,
the reaction of cyclohexanone (5) with 2-propanol cata-
lyzed by the [Ir(cod)Cl]2/dppp/Cs2CO3 afforded cyclohex-
anol (6) in good yield (Table 3, entry 1). Acyclic ketones
such as 2-octanone, however, were difficult to reduce
under these reaction conditions, probably because the
resulting 2-octanol is a better hydrogen source than
2-propanol (Table 3, entry 2). Hence, when excess 2-pro-
panol was employed, 2-octanol was obtained in higher
yield (Table 3, entry 3). Additionally, styrene was also
hydrogenated to ethylbenzene in excellent yield (Table
3, entry 6). Quite recently, an efficient transfer hydro-
genation of simple alkynes and alkenes with methanol
catalyzed by an hydrido(methoxo)iridium(III) complex
has been reported.7
a
Substrate (0.5 mmol) was allowed to react with 2-propanol (5.0
mmol) in the presence of a catalytic amount of [Ir(cod)Cl]2 (2 mol
%), dppp (2 mol %), and Cs2CO3 (2 mol %) in toluene (0.5 mL) at
b
80 °C for 4 h. [Ir(cod)Cl]2 (1 mol %), dppp (1 mol %), Cs2CO3 (1
mol %). c Cs2CO3 (1 mol %). 15 h. e 75 °C, 6 h.
d
hydrogenation of saturated ketones to alcohols. Thus, we
next examined the reduction of a 1:1 mixture of a R,â-
unsaturated ketone and a saturated one catalyzed by
[Ir(cod)Cl]2/dppp/Cs2CO3 system. The reaction of a 1:1
mixture of cyclopentenone (3) (0.5 mmol) and cyclohex-
anone (5) (0.5 mmol) with 2-propanol (5 mmol) using [Ir-
(cod)Cl]2 (0.01 mmol) in the presence of dppp (0.01 mmol)
and Cs2CO3 (0.01 mmol) was performed. Figure 1 shows
the time dependence curves for the production of cyclo-
pentanone (4) and cyclohexanol (6). As expected, the
reduction of 3 took place faster compared with that of 5,
suggesting that the iridium complex coordinates prefer-
entially to the double bond of the R,â-unsaturated ketone
to that of the carbonyl group.
Discu ssion
The selective reduction of conjugated double bonds of
R,â-unsaturated carbonyl compounds with 2-propanol as
a hydrogen source was successfully achieved by the
catalysis of [Ir(cod)Cl]2 in combination with dppp and Cs2-
CO3. The most important feature in this reaction is that
the resulting ketones were not further reduced to alcohols
except in the case of 3-methyl-2-cyclohexenone, although
the present catalyst system also promotes the transfer
Tani et al. reported that simple alkynes and alkenes
were reduced with methanol under the influence of an
iridium hydrido(methoxo) complex prepared by the reac-
tion of [Ir(dpdp)Cl]2 (dpdp ) 2,2′-bis(diphenylphosphino)-
1,1′-biphenyl) with methanol.7,8 They suggested that an
iridium dihydride complex was formed and acted as the
real catalyst. The coordination of the iridium complex to
(8) Tani, K.; Iseki, A.; Yamagata, T. Angew. Chem. Ind. Ed. 1998,
37, 3381.
(7) Tani, K.; Iseki, A.; Yamagata, T. Chem. Commun. 1999, 1821.

4712 J . Org. Chem., Vol. 66, No. 13, 2001
Sakaguchi et al.
Ta ble 3. Tr a n sfer Hyd r ogen a tion of Sever a l Ca r bon yl
Com p ou n d s a n d Alk en es by th e
is also possible, the formation of allylic alcohol was not
observed at all during the reaction course. In addition,
the selective conversion of allylic alcohol to carbonyl
compound is found to be difficult under these reaction
conditions. Treatment of 2-cyclohexen-1-ol by the [Ir(cod)-
Cl]2/dppp/Cs2CO3 system produced a mixture of cyclo-
hexanone, cyclohexanol, and 3-cyclohexen-1-ol in the
presence or absence of 2-propanol, respectively (eq 2).
These observations suggested that the present reduction
of R,â-unsaturated carbonyl compound did not involve the
formation of allylic alcohol as an intermediate.
a
[Ir (cod )Cl]2/d p p p /Cs2CO3
In conclusion, the chemoselective transfer hydrogena-
tion of R,â-unsaturated carbonyl compounds to saturated
compounds has been accomplished by the use of the
combined catalyst system of [Ir(cod)Cl]2/dppp/Cs2CO3.
This method was also effective for the reduction of both
simple carbonyl compounds and alkenes. Furthermore,
in the reaction of a 1:1 mixture of conjugated enone and
saturated ketone with 2-propanol catalyzed by the
[Ir(cod)Cl]2/dppp/Cs2CO3 system, the reduction of the R,â-
unsaturated ketone took place in preference to that of
the saturated ketone.
a
Reaction was run as shown in Table 2; see footnote a.
b
[Ir(cod)Cl]2 (1 mol %), dppp (1 mol %), Cs2CO3 (1 mol %).
c [Ir(cod)Cl]2 (4 mol %), dppp (4 mol %), Cs2CO3 (4 mol %). 15 h.
d
e 2-Propanol (10 mmol) was used. f Cs2CO3 (1 mol %).
Exp er im en ta l Section
Gen er a l P r oced u r es. 1H and 13C NMR spectra were
measured at 270 and 67.5 MHz, respectively, in CDCl3 with
TMS as the internal standard. IR spectra were measured as
films on NaCl plates. GLC analysis was performed with a
flame ionization detector using a 1 mm × 30 m capillary
column (OV-1). All starting materials were commercially
available and used after distillation or recrystallization.
Gen er a l P r oced u r e for th e Red u ction of r,â-Un sa tu r -
a ted Ca r bon yl Com p ou n d s w ith 2-P r op a n ol. To a toluene
solution (0.5 mL) of [Ir(cod)Cl]2 (0.005 mmol), dppp (0.005
mmol), and Cs2CO3 (0.005 mmol) were added R,â-unsaturated
compounds (0.5 mmol) and isopropyl alcohol (5 mmol) under
Ar, and then the reaction mixture was stirred at 80 °C for 4
h. After quenching with wet ether, the products were isolated
by column chromatography (230-400 mesh silica gel, hexane).
After the reaction, the GC and GC-MS analyses were per-
formed. The yields of products were estimated from the peak
areas based on the internal standard technique using GC. The
products except for 3-cycohexen-1-ol9 were commercially avail-
able and were identified through comparison of the isolated
product with an authentic sample.
F igu r e 1. Time-dependence curves for the reduction of a 1:1
mixture of cyclopentenone (3) and cyclohexanone (5) by the
[Ir(cod)Cl]2/dppp/Cs2CO3 system. A mixture of 3 (0.5 mmol)
and 5 (0.5 mmol) was allowed to react with 2-propanol (5.0
mmol) in the presence of a catalytic amount of [Ir(cod)Cl]2 (0.01
mmol), dppp (0.01 mmol) and Cs2CO3 (0.01 mmol) in toluene
(0.5 mL) at 80 °C.
alkene followed by hydride insertion gave the corre-
sponding alkane. The reaction pathway of the present
transfer hydrogenation by [Ir(cod)Cl]2/dppp/Cs2CO3 is not
fully confirmed at this stage, but it seems likely that the
reaction proceeds through a similar pathway as reported
by Tani et al. The reaction may be initiated by the
coordination of an iridium hydride complex, generated
in situ from [Ir(cod)Cl]2-dppp complex and 2-propanol
under the influence of Cs2CO3, to R,â-unsaturated car-
bonyl compound followed by hydrogen transfer to a
conjugated double bond giving a saturated carbonyl
compound.
2,6-Dim eth yl-2-h ep ten -4-on e: 1H NMR (CDCl3/TMS) δ
5.99 (s, 1H), 2.20 (d, J ) 6.7 Hz, 2H), 2.08-2.05 (m, 1H), 2.07
(s, 3H), 1.81 (s, 3H), 0.85 (d, J ) 6.7 Hz, 6H); 13C NMR (CDCl3/
TMS) δ 201.1, 141.0, 124.1, 53.3, 27.6, 25.1, 22.6, 20.6.
J O0156722
(9) (a) Harris, N. J .; Gajewski, J . J . J . Am. Chem. Soc. 1994, 116,
6121. (b) Dzingeleski, G. D.; Blotny, G.; Pollack, R. M. J . Org. Chem.
1990, 55, 1019. (c) Marton, D.; Slaviero, P.; Tagliavini, G. Tetrahedron
1989, 45, 7099.
Although another reaction path via the formation of
allylic alcohol followed by double bond migration to enol