Generally applicable and efficient esterification of aldehydes with alcohols catalyzed by cyclopalladated ferrocenylimine

Article abstract of DOI:10.1002/aoc.3069

The palladacycle-catalyzed esterification of a variety of aldehydes with alcohols was developed. This reaction allows formation of esters in moderate to excellent yields not only for various aldehydes but also alcohols. In addition, the esterification could proceed well under mild conditions with a low catalyst loading of 0.0625 mol%. Copyright

Full text of DOI:10.1002/aoc.3069

Full Paper
Received: 10 July 2013
Revised: 18 August 2013
Accepted: 23 August 2013
Published online in Wiley Online Library: 6 November 2013
(wileyonlinelibrary.com) DOI 10.1002/aoc.3069
Generally applicable and efficient esterification
of aldehydes with alcohols catalyzed by
cyclopalladated ferrocenylimine
Gaizhi Maa, Yuting Lenga*, Huijie Qiaoa, Fan Yanga, Shiwei Wangb
and Yangjie Wua*
The palladacycle-catalyzed esterification of a variety of aldehydes with alcohols was developed. This reaction allows formation of
esters in moderate to excellent yields not only for various aldehydes but also alcohols. In addition, the esterification could proceed
well under mild conditions with a low catalyst loading of 0.0625mol%. Copyright © 2013 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web site.
Keywords: cyclopalladated ferrocenylimine; esterification; aldehydes; alcohols
method for the synthesis of esters via cross-coupling reaction of
Introduction
aldehydes with alcohols in the presence of cyclopalladated
ferrocenylimines I, II (Fig. 1).[10]
Ester groups generally exist in bulk chemicals, fine chemicals,
natural products and polymers, and are known to be highly im-
portant and abundant functional groups in organic synthesis.[1]
The direct transformation of aldehydes to esters under mild
Results and Discussion
conditions is a useful transformation, especially in the synthesis
of different natural products.[2] However, current protocols to
In our initial study, we examined the effects of solvents, various
esterify an aldehyde with an alcohol require oxidation to the acid
catalysts and bases on the reaction of aldehydes with alcohols.
in advance. Such transformations have been achieved, for exam-
The results are summarized in Table 1. The reaction of aldehydes
ple, with peroxo species generated by the reaction of hydrogen
with alcohols was carried out with different catalysts, and the
peroxide with vanadium(V)[3,4] and with methyltrioxorhenium
desired product was obtained in relatively high yields (92%) un-
(VII) (MTO) in the presence of co-catalysts such as chloride or
der the catalysis of cyclopalladated ferrocenylimine I (0.0625%)
bromide ions.[3–5] Further efforts have been devoted to the direct
and the ligand PPh3 (2.5%) in comparison with cases using other
synthesis of esters from the oxidative esterification of aldehydes
Pd catalysts, such as Pd(PPh3)4 or PdCl2 (Table 1, entries 1–4).
with alcohols, in which stoichiometric amounts of metal salts like
After screening of a variety of solvents (entries 4–8), it was revealed
KHSO5, oxone or MnO2 have to be employed as oxidants.[6] Very
that THF seems to be optimal (Table 1, entry 4). Based on the roles
recently, in the development of both selective palladium-
of bases in transition-metal catalyzed organic reactions reported by
catalyzed aldehyde formation and oxidative esterification, signif-
Ouyang and Xi,[11] the impact of the bases on the efficiency of catal-
icant progress has been achieved by several groups, such as
ysis was investigated (Table 1, entries 9–14), and Cs2CO3 turns out
those of Lei, Beller and others.[7,8] Although several methods have
to be the best option to give the desired product in 92% yield
been reported for the direct preparation of aldehydes to esters,
(Table 1, entry 4). Such a high activity of the catalytic system allows
those methods usually require a high loading catalyst, extremes
further shortening of the reaction time to 12 h (Table 1, entry 15).
of temperature, long reaction times, inert atmosphere, photo-
Under such mild conditions, comparable yield (93%) of coupling
chemical conditions, poisonous and polluting reagents, media-
tors or co-catalysts. Some of these reaction conditions are also
unsatisfactory for the specific oxidation of aldehydes containing
deactivated, hindered and double-bond-containing substrates,
resulting in over-oxidation and undesirable products, proceeding
non-selectively, and affording the desired product in poor to
moderate yields. Therefore, a milder, convenient and efficient
catalytic system still needs to be developed.
Cyclopalladated ferrocenylimines as one type of readily pre-
pared complexes with good stability and convenient manipula-
tion have been widely applied to various coupling reactions.[9]
As our ongoing endeavor toward seeking a new palladacycle
application, herein we report a generally applicable and efficient
*
Correspondence to: Yangjie Wu and Yuting Leng, College of Chemistry and
Molecular Engineering, Key Laboratory of Applied Chemistry of Henan Universities,
Key laboratory of Chemical Biology and Organic Chemistry of Henan
Province, Zhengzhou University, Zhengzhou, Henan 450052, People’s
Republic of China. E-mail: wyj@zzu.edu.cn; yutingleng@zzu.edu.cn
a College of Chemistry and Molecular Engineering, Key Laboratory of Applied
Chemistry of Henan Universities, Key laboratory of Chemical Biology and Organic
Chemistry of Henan Province, Zhengzhou University, Zhengzhou, Henan, 450052,
People’s Republic of China
b College of Mechanics and Engineering Science, Zhengzhou University,
Zhengzhou, Henan, 450001, People’s Republic of China
Appl. Organometal. Chem. 2014, 28, 44–47
Copyright © 2013 John Wiley & Sons, Ltd.

Palladacycle-catalyzed esterification of aldehydes with alcohols
of entry 23 are relatively good, the conditions for entry 15 should
be the better because the synthesis step of catalyst I is shorter
than II.
N
N
Cl
L
With the optimized reaction conditions in hand, the substrate
scope was then investigated. As shown in Table 2, the esterifica-
tion of various arylaldehydes (1a–1p) with alcohols (2a–2i) under
the catalysis of I/PPh3 is quite general. The reaction proceeded
smoothly to afford the esterification products (3a–3y) in moder-
ate to excellent isolated yields (50–97%). For the substrates, the
electronic property of substituents (R1) on the aromatic rings of
aryl aldehyde had no significant impact on yields of the esterifica-
tion reactions. Arylaldehyde, having an electron-donating or elec-
tron-withdrawing group, reacted with the alcohol perfectly to
afford the corresponding desired product in good to excellent
yields (Table 2, entries 1–19). However, steric bulky substituents
(R1) on the aromatic rings of aldehydes would hinder the trans-
formation. When the arylaldehyde possessed two groups in the
ortho position, the corresponding product was obtained at a
lower yield of 55% (Table 2, entry 20). It is worth pointing out that
Pd
Fe
Fe
Cl
I
II
L= PPh3,
Figure 1. Palladacycles I, II.
product was isolated. Most interestingly, the cross-coupling reac-
tion even proceeds smoothly for 8 h with moderate yield (Table 1,
entry 16). However, the desired product was not obtained in the
absence of catalyst or PPh3, and the reaction could not proceed
nearly so well, affording a trace of product in the lower loading
of PPh3 or catalyst II (Table 1, entries 18–22). Although the results
Table 1. Effects of solvents, catalysts, bases, temperature and oxidants on the reaction of aldehydes with alcoholsa
Entry
Catalyst
Pd[PPh3]4(1%)
Solvent
Base
T (°C)
t (h)
Yield (%)b
1
THF
THF
THF
THF
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
CsF
70
70
70
70
85
110
90
85
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
20
20
20
20
20
20
20
20
20
20
20
20
20
20
12
8
10
89
2
PdCl2 (5%) + PPh3 (10%)
II (2%)
3
91
4
I (0.0625%) + PPh3 (2.5%)
I (0.0625%) + PPh3 (2.5%)
I (0.0625%) + PPh3 (2.5%)
I (0.0625%) + PPh3 (2.5%)
I (0.0625%) + PPh3 (2.5%)
I (0.0625%) + PPh3 (2.5%)
I (0.0625%) + PPh3 (2.5%)
I (0.0625%) + PPh3 (2.5%)
I (0.0625%) + PPh3 (2.5%)
I (0.0625%) + PPh3 (2.5%)
I (0.0625%) + PPh3 (2.5%)
I (0.0625%) + PPh3 (2.5%)
I (0.0625%) + PPh3 (2.5%)
I (0.0625%) + PPh3 (2.5%)
92
5
ClCH2CH2Cl
1, 4-Dioxane
n-Hexane
CH3CN
THF
67
6
83
7
81
8
53
9
30
10
11
12
13
14
15
16
17
18
19
20
21
22
23
THF
K3PO4
K2CO3
KOH
47
THF
47
THF
65
THF
DBU
80
THF
NEt3
87
93a/76c
THF
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
THF
75
THF
4
30
n.d.d
THF
12
12
12
12
12
12
I (0.0625%) + PPh3 (1.25%)
I (0.0625%) + PPh3 (0.625%)
I (0.0625%)
THF
39
THF
23
THF
Trace
5
II (0.0625%)
THF
II (0.125%) + PPh3 (2.5%)
THF
90
aReaction conditions: 1a (2 mmol), 2a (3 mmol), base (2 mmol), BnCl (benzyl chloride) (2 mmol), catalyst I (0.0625 mol%) + PPh3 (2.5 mol%), solvent
(2 ml), under nitrogen.
bIsolated yields.
cBnBr (benzyl bromide) (2 mmol).
dNot determined.
Appl. Organometal. Chem. 2014, 28, 44–47
Copyright © 2013 John Wiley & Sons, Ltd.
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G. Ma et al.
Table 2. Esterification of a variety of aldehydes with primary and secondary alcoholsa
Entry
R1
R2
Product
Yield (%) b
1
Ph
1a
1a
1a
1b
1d
1c
1e
1f
Me
2a
2c
2b
2b
2b
2b
2b
2b
2b
2b
2d
2d
2d
2d
2d
2d
2d
2h
2h
2d
2i
3a
3b
3c
3d
3e
3f
89
80
93
90
88
87
95
95
95
84
96
97
96
87
95
93
84
95
93
55
73
74
67
72
65
2
Ph
Iso-pentyl
n-Butyl
n-Butyl
n-Butyl
n-Butyl
n-Butyl
n-Butyl
n-Butyl
n-Butyl
n-Hexyl
n-Hexyl
n-Hexyl
n-Hexyl
n-Hexyl
n-Hexyl
n-Hexyl
n-Octyl
n-Octyl
n-Hexyl
2-Octyl
2-Octyl
2-Octyl
2-Octyl
Cyclohexyl
3
Ph
4
4-ClC6H4
5
4-MeC6H4
2-MeC6H4
4-MeOC6H4
3-MeOC6H4
3-NO2C6H4
3,5-Me2C6H3
4-MeOC6H4
3-ClC6H4
6
7
3g
3h
3i
8
9
1g
1h
1e
1k
1d
1g
1l
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
3j
3k
3l
4-MeC6H4
3-NO2C6H4
4-CF3C6H4
4-NO2C6H4
2-Naphthyl
4-NO2C6H4
4-MeOC6H4
2,4,6-Me3C6H2
4-MeOC6H4
4-CF3C6H4
4-NO2C6H4
3-ClC6H4
3m
3n
3o
3p
3q
3r
1n
1o
1n
1e
1j
3s
3t
1e
1l
3u
3v
3w
3x
3y
2i
1n
1k
1b
2i
2i
4-ClC6H4
2g
aReaction conditions: 1a–1o (2 mmol), 2a–2i (3 mmol), base (2 mmol), BnCl (2 mmol), catalyst I (0.0625 mol%), PPh3 (2.5 mol%), solvent (2 ml),
under nitrogen.
bIsolated yield.
the reactions for both primary and secondary alcohols, especially
for the unstable cyclohexanol, proceeded smoothly to afford the
products in moderate to good yields under a low catalyst loading
Table 3. Esterification of a variety of aliphatic aldehydes with benzyl
alcoholsa
of 0.0625 mol% (Table 2, entries 21–25).
Results from the esterification of a variety of aldehydes with
primary and secondary alcohols were encouraging, prompting
us to check whether the esterification of a variety of aliphatic al-
dehydes with benzyl alcohol could work in the same catalytic sys-
tem. Thus we turned our attention to the aliphatic aldehydes for
the palladium-catalyzed esterification with benzyl alcohol, and
the results are shown in Table 3. Both chain aldehyde and
cyclohexyl aldehyde could react well with benzyl alcohol to af-
ford the products in satisfactory yields. For example, the
reaction of n-caproaldehyde with anisalcohol took place success-
fully and the desired product was obtained with 78% yield
(Table 3, entry 1). Similarly, cyclohexylaldehyde also could pro-
ceed smoothly with anisalcohol or 1-naphthalenemethanol and
high yields (87% and 86%, respectively) were obtained (Table 3,
entries 2 and 3).
Entry
R1
R2
3z–3ϕ Yield (%)b
1
2
3
n-Pentyl
1p 4-Methoxybenzyl 2f
3z
3δ
3ϕ
78
87
86
Cyclohexyl 1i
Cyclohexyl 1i
4-Methoxybenzyl 2f
Naphthylmethyl 2e
aReaction conditions: 1i–1p (2 mmol), 2e-2f (3 mmol), base
(2 mmol), BnCl (2 mmol), catalyst I (0.0625 mol %), PPh3 (2.5 mol
%), solvent (2 ml), under nitrogen.
bIsolated yield.
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Copyright © 2013 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2014, 28, 44–47

Palladacycle-catalyzed esterification of aldehydes with alcohols
Acknowledgments
Conclusions
We are grateful to the National Natural Science Foundation of China
(Nos. 20772114, 21172200) and the Innovation Fund for Outstanding
Scholar of Henan Province (Nos. 0621001100) and the Education
Department of Henan province science and technology research
projects (No.13A150681) for financial support of this research.
In summary, we have described a highly efficient catalytic sys-
tem for the reaction of a variety of aldehydes with alcohols by
using cyclopalladated ferrocenylimine (I) as the catalyst and
PPh3 as a ligand. A wide range of substrates could be used in
this system: aryldehydes and aliphatic aldehydes including
chain aldehyde and cyclohexyl aldehyde all work well with
primary, secondary alcohols and benzyl alcohols, affording
moderate to excellent yields. Further studies on extending
the application of this reaction in organic synthesis are ongoing
in our laboratory.
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Butyl 3,5-dimethyl benzoate (3j)
Colorless oil; 1HNMR (400MHz, CDCl3): δ = 7.69 (s, 2H of 2- and 6- on
C6H3), 7.20 (s, 1H of 4- on C6H3), 4.34 (d, 2 H, O―CH2, J = 6.7Hz), 2.40
(s, 6 H, aryl-CH3), 1.82–1.75 (m, 2 H, CH3CH2CH2), 1.56–1.47(m, 2 H,
CH3CH2CH2), 1.02 (t, 3 H, C―CH3, J = 7.4 Hz); 13C NMR (100MHz,
CDCl3): δ = 167.1 (C O), 137.9 (C of 3- on C6H3) , 134.5 (C of 4- on
C6H3), 130.4 (C―C O), 127.3 (C of 2- and 4- on C6H3), 64.7
(O―CH2), 30.9 (CH3CH2CH2), 21.2 (aryl-CH3), 19.3 (CH3CH2CH2),
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3h,[8] 3i,[19] 3k,[20] 3l,[21] 3m,[22] 3n,[23] 3o,[17] 3p,[24] 3q,[25] 3r,[26]
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3ϕ[35] were characterized by comparing their 1H NMR and13C
NMR spectra with those mentioned in the references.
Supporting Information
Additional supporting information may be found in the online
version of this article at the publisher’s web site.
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