Iridium-catalyzed oxidative esterification reaction of aliphatic aldehydes and olefinic alcohols with precoordination of the double bond of alcohols to iridium

Article abstract of DOI:10.1016/j.tetlet.2005.04.093

A novel iridium-catalyzed oxidative esterification reaction of aliphatic aldehydes and olefinic alcohols in toluene was found under mild conditions of [IrCl(cod)]₂ (5 mol %) in combination with K₂CO ₃ (10 mol %) at rt.

Full text of DOI:10.1016/j.tetlet.2005.04.093

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4639–4642
Iridium-catalyzed oxidative esterification reaction of
aliphatic aldehydes and olefinic alcohols with precoordination of
the double bond of alcohols to iridium
Syun-ichi Kiyooka,* Mahuyu Ueno and Eri Ishii
Department of Material Science, Faculty of Science, Kochi University, Akebono-cho, Kochi 780-8520, Japan
Received 7 April 2005; revised 23 April 2005; accepted 27 April 2005
Available online 23 May 2005
Abstract—A novel iridium-catalyzed oxidative esterification reaction of aliphatic aldehydes and olefinic alcohols in toluene was
found under mild conditions of [IrCl(cod)]2 (5 mol %) in combination with K2CO3 (10 mol %) at rt.
ꢀ 2005 Elsevier Ltd. All rights reserved.
Iridium complexes are known to be effective for isomer-
ization of allylic alcohols to aldehydes and ketones.1,2
The transition metal-catalyzed isomerization of allylic
alcohols is considered to proceed via the process invol-
ving a metal enolate, as depicted in Scheme 1, from
the standpoint of the observation of tandem allylic alco-
hol isomerization aldol reaction.3,4 On the basis of the
mechanism, the possibility and the utilization of atom-
economical generation of transition metal enolates can
be strongly expected during the isomerization. We
started the study of iridium-catalyzed isomerization
reaction of allylic alcohols for the purpose of trapping
such enolates. At the preliminary stage, we incidentally
found the formation of esters in the iridium-catalyzed
isomerization reaction of cinnamyl alcohol. We disclose
herein a novel iridium-catalyzed oxidative esterification
of aliphatic aldehydes with olefinic alcohols.
A dramatic rate enhancement by the presence of a cata-
lytic amount of base (K2CO3) was observed in ruthe-
nium-catalyzed isomerization of allylic alcohols to
saturated ketones.5 A similar effect of K2CO3 was also
observed in iridium-catalyzed Oppenauer-type oxida-
tions.6 While nucleophilic transition metal complexes,
like IrCl(trialkylphosphine)3, are known to undergo oxi-
dative addition of alcohols as to give hydrido-alkoxo
complexes,7 the addition was difficult without bases in
the case of [IrCl(cod)]2. Thus, we chose mild conditions
([IrCl(cod)]2 (5 mol %), rt, 12 h, THF) in combination
with K2CO3 (10 mol %) for our iridium-catalyzed allylic
isomerization. As expected, secondary allylic alcohols
smoothly underwent the isomerization reaction to give
the corresponding ketones in good yields (Scheme 2).
Primary allylic alcohols, however, exhibited different
behaviors. Reaction of cinnamyl alcohol under the same
conditions surprisingly gave two types of esters along
with a small amount of hydrocinnamaldehyde (Scheme
3). Formation of the esters is formally corresponding
to esterification of hydrocinnamic acid with hydrocinn-
amyl and cinnamyl alcohols. Consequently, the whole
process of ester formation must be accounted for by
M
M
H
O
H
O
"M"
OH
Metal enolate
OH
O
H
- "M"
5 mol% of [IrCl(cod)]2
OH
O
10 mol% of K2CO3
Scheme 1.
R
R
THF, rt, 12 h
R:
67%
96%
Keywords: [IrCl(cod)]2; Oxidative esterification; Precoordination to
olefin.
R:
Ph-
*
Corresponding author. Tel.: +81 88 844 8295; fax: +81 88 844
8359; e-mail: kiyooka@cc.kochi-u.ac.jp
Scheme 2.
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.04.093

4640
S. Kiyooka et al. / Tetrahedron Letters 46 (2005) 4639–4642
5 mol% of [IrCl(cod)]2
10 mol% of K2CO3
and cinnamyl alcohol with assistance of K2CO3. The
CHO
subsequent insertion of the aldehyde, which was in
advance produced via isomerization, took place to afford
an iridium acetal intermediate, followed by oxidative
hydrogen transfer (b-hydrogen elimination)6,10 to the
unsaturated aldehyde in delivering a hydride iridium
complex. At the final step the alkoxo complex is recycled
to form dihydride species, which can serve some reduc-
tion of unsaturated bonds of the product ester and/or
the starting alcohol. It is still uncertain whether the
cod ligand remains unchanged as it is.11
Ph
+
OH
Ph
THF, rt, 12 h
3%
O
O
+
Ph
O
Ph
Ph
O
Ph
7%
unsaturated ester
31%
saturated ester
Scheme 3.
C–O bond formation and subsequent oxidation, accom-
panied by isomerization. Ruthenium-catalyzed oxidative
transformation of aldehydes with alcohols to esters was
observed at a severely elevated temperature (180 ꢁC).8
Recently, esters could be formed by insertion of alde-
hyde into a rhodium alkoxo complex and subsequent
b-hydrogen elimination from the resulting alkoxo com-
plex.9 But, to our knowledge, direct observations of such
a condensation between an aldehyde and an alcohol
have not been reported yet. A plausible mechanism is
shown in Scheme 4. The reaction might initiate with
the iridium alkoxo complex formed from [IrCl(cod)]2
The condensation was continuously investigated to real-
ize the general iridium-catalyzed oxidative esterification
starting from a primary allylic alcohol and an aldehyde.
Reaction of hydrocinnamaldehyde with cinnamyl alco-
hol resulted in a more good yield, compared with the
case of only cinnamyl alcohol (Scheme 3), to give the
same ester pair with hydrocinnamyl alcohol (Table 1).
The best result in toluene was obtained with a 1:2 molar
ratio of the starting aldehyde to alcohol (entry 3).
Acetonitrile was inadequate for the reaction, probably
owing to its high coordination ability (entry 4). An
important limitation was simultaneously found that
the reaction with alcohols, not having an olefinic moiety,
did not work at all. The precoordination of the olefinic
moiety might be essential for this condensation. Iridium-
catalyzed allylic isomerization is dispensable for this oxi-
dative esterification. Cross condensation, starting with
an allylic alcohol and an aldehyde of different structure,
can be considered. In practice, the cross condensation
occurred very smoothly (Table 2):12 Hydrocinnam-
aldehyde and 2-methylbutyraldehyde were used as typi-
cal primary and secondary aliphatic aldehydes. Despite
the structural difference of the aldehydes, primary and
secondary allylic alcohols underwent the iridium-cata-
lyzed oxidative esterification reaction to afford the corre-
sponding esters (entries 1–5 and 9–11). When secondary
alcohols were used, the obtained products were only
unsaturated esters (entries 4, 5, and 11). Control experi-
ments clarified an interesting feature of this reaction
(entries 6–8) in which olefinic alcohols, having a double
bond far from the hydroxy function, exactly worked.
Even 5-hexen-1-ol could give the corresponding esters
in a satisfactory yield (entry 8). Presumably, the remote
double bond also works for the precoordination of
[IrCl(cod)]2
+
K2CO3
+
Ph
OH
Ph
O
to reduction of unsaturated
double bonds
Ph
H
Ir
Ir
O
H
Ir
H
16e
O
Ph
O
Ph
O
Ph
OH
Ph
H
O
Ir
Ph
Ph
O
Ph
O
H
O
Ph
(It is uncertain whether the cod ligand remains unchanged over the whole process)
Scheme 4. A plausible mechanism via insertion of an aldehyde into an
alkoxo complex.
Table 1. Iridium-catalyzed oxidative esterification of hydrocinnamaldehyde with cinnamyl alcohol
5 mol%[IrCl(cod)]2, 10 mol%K2CO3
CHO
+
Ph
Ph
OH
solvent,rt, 12h
O
O
+
Ph
O
Ph
O
Ph
Ph
Entry
Aldehyde/alcohol
Solvent
% Yield of esters
(unsaturated/saturated)
1
2
3
4
1:1
1:2
1:2
1:2
THF
THF
46 (3:1)
60 (2:1)a
97 (3:2)a
No reaction
Toluene
CH3CN
a The isolated yields were determined, based on the starting aldehyde, although the amount of the aldehyde might be partially increased by
isomerization of cinnamyl alcohol during the reaction.

S. Kiyooka et al. / Tetrahedron Letters 46 (2005) 4639–4642
4641
Table 2. Iridium-catalyzed oxidative esterification reaction with a variety of olefinic alcoholsa
Entry
1
Aldehydes
Alcohols
OH
% Yield of esters
CHO
65
71
Ph
Ph
Ph
O
Ph
O
( 5 : 1 )
O
O
O
O
CHO
OH
2
Ph
Ph
O
O
Ph
O
O
( 5 : 1 )
CHO
CHO
CHO
3
4
5
96
87
88
Ph
Ph
Ph
Ph
OH
OH
( 5 : 1 )
O
Ph
O
O
O
OH
Ph
Ph
O
O
O
CHO
CHO
CHO
6
OH
90
85
76
73
85
Ph
O
Ph
Ph
Ph
2
( 4 : 1 )
O
O
O
7
OH
Ph
Ph
O
O
Ph
( 5b : 1 )
O
3
O
8
OH
Ph
O
4
( 5b : 1 )
O
O
O
CHO
9
O
O
O
O
( 3 : 1 )
O
CHO
CHO
10
OH
( 3 : 1 )
O
OH
11
77
O
bThe esters are containing isomeric inner olefins.
a The reaction conditions of entry 3 in Table 1 were used.
iridium to form the resulting alkoxo complex and the
outer-sphere attack of the pendant alkoxo moiety onto
the coordinated aldehyde results in the subsequent
C–O bond formation.
expected ester. The electron-attractive character of the
aromatic moiety, compared to that of aliphatic one,
might be suitable to undergo a tandem isomerization
aldol reaction.3 The major products in the reaction were
composed of aldol products and their derivatives
(Scheme 5). The derivatives are considered to result
from the extended oxidative esterification of the aldol
products and the following cyclization.
In addition, aromatic aldehyde showed a little bit differ-
ent behavior in the reaction. The reaction of benzalde-
hyde with crotyl alcohol gave a small amount of the
OH
O
O
O
H
β
O
α
+
OH
+
PhCHO
32% (syn/anti = 3 : 1)
15% (syn/anti = 2 : 1
on α,β-isomers)
Ir
O
O
O
O
+
Ph
H
4%
Scheme 5.

4642
S. Kiyooka et al. / Tetrahedron Letters 46 (2005) 4639–4642
5. Ba¨ckvall, J.-E.; Andresson, U. Tetrahedron Lett. 1993, 34,
5459.
Acknowledgements
6. (a) Fujita, K.; Furukawa, S.; Yamaguchi, R. J. Organo-
met. Chem. 2002, 649, 289; (b) Suzuki, T.; Morita, K.;
Tsuchida, M.; Hiroi, K. J. Org. Chem. 2003, 68, 1601.
7. Blum, O.; Milstein, D. J. Am. Chem. Soc. 2002, 124,
11456.
We thank a Grant-in-Aid for Scientific Research of
Japan Society for the Promotion of Science.
References and notes
8. Murahashi, S.; Naota, T.; Ito, K.; Maeda, Y.; Taki, H.
J. Org. Chem. 1987, 52, 4319.
9. (a) Krug, C.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124,
1674; (b) Han, R.; Hillhouse, G. L. J. Am. Chem. Soc.
1997, 119, 8135.
1. Davies, S. G. Organotransition Metal Chemistry, Applica-
tions to Organic Synthesis; Pergamon: Oxford, 1982, pp
282–290.
10. Suzuki, T.; Morita, K.; Tsuchida, M.; Hiroi, K. Org. Lett.
2000, 4, 2361.
2. (a) Pannetier, G.; Bonnaire, R.; Fouqeroux, P. J. Organo-
metal. Chem. 1971, 30, 411; (b) Baudry, D.; Ephritikhine,
M.; Felkin, H. Nouveau J. Chimie 1977, 2, 355; (c)
Ohmura, T.; Shirai, Y.; Yamamoto, Y.; Miyaura, N.
Chem. Commun. 1998, 1337.
´
11. Martın, M.; Sola, E.; Torres, O.; Plou, P.; Oro, L. A.
Organometallics 2003, 22, 5406.
12. General procedure for the oxidative esterification: To an
oven-dried round bottomed flask were added [IrCl(cod)]2
(33 mg, 0.05 mmol) and K2CO3 (14 mg, 0.1 mmol) in
toluene (2 mL) under Ar. To this solution were slowly
added aldehyde (1 mmol) and alcohol (2 mmol). The
reaction mixture was stirred at rt for 12 h. The reaction
was quenched with saturated NH4Cl (5 mL). The organic
layer was separated and the aqueous layer was extracted
with ether (10 mL · 3). The combined organic layers were
dried over anhydrous MgSO4. After evaporation of the
solvent, the crude residue was purified by flash column
chromatography on silica gel to give the resulting esters.
3. Tandem isomerization aldol condensations using allylic
´
alcohols: Fe: (a) Uma, R.; Gouault, N.; Crevisy, C.; Gree,
R. Tetrahedron Lett. 2003, 44, 6187; (b) Crevisy, C.;
´
´
´
Wietrich, M.; Le Boulaire, V.; Uma, R.; Gree, R.
Tetrahedron Lett. 2001, 42, 395; Rh: (a) Gazzard, L. J.;
Motherwell, W. B.; Sandham, D. A. J. Chem. Soc., Perkin
´
Trans. 1 1999, 979; (b) Uma, R.; Davies, M.; Crevisy, C.;
´
Gree, R. Tetrahedron Lett. 2001, 42, 3069.
4. A hydrido-p-allylic intermediate was also proposed: Ber-
gens, S. H.; Bosnich, B. J. Am. Chem. Soc. 1991, 113,
958.