Oxidant controlled Pd-catalysed selective oxidation of primary alcohols

Article abstract of DOI:10.1039/c2cc38086b

The oxidant controlled palladium catalysed selective oxidation of primary alcohols to aldehydes or esters was investigated. The electronic properties of the benzylic alcohols and the structure of the oxidant are both important factors in controlling the selectivity between aldehydes and esters. A covalent benzyl ligand derived from BnCl provides η³ coordination to the Pd centre. This covalent ligand is the key to the selective oxidative esterification of primary alcohols.

Full text of DOI:10.1039/c2cc38086b

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Oxidant controlled Pd-catalysed selective oxidation of
primary alcohols†
Cite this: Chem. Commun., 2013,
49, 1324
a
a
Chao Liu,z Shan Tangz and Aiwen Lei*ab
Received 8th November 2012,
Accepted 27th December 2012
DOI: 10.1039/c2cc38086b
www.rsc.org/chemcomm
The oxidant controlled palladium catalysed selective oxidation of
primary alcohols to aldehydes or esters was investigated. The electronic
properties of the benzylic alcohols and the structure of the oxidant are
both important factors in controlling the selectivity between aldehydes
and esters. A covalent benzyl ligand derived from BnCl provides
Scheme 1 Pd catalysed oxidation of primary alcohols.
g3 coordination to the Pd centre. This covalent ligand is the key to bound benzyl group to promote the selective esterification.6 Mean-
the selective oxidative esterification of primary alcohols.
while, an alpha-chloro carbonyl compound was found to be effective
for selective aldehyde formation. To obtain more details about the
The oxidation of alcohols in the presence of palladium catalysts has difference between these two types of oxidants, further investigations
been a fundamental research area in the chemical synthesis com- were carried out on the direct oxidation of primary alcohols by using
munity.1 A vast number of transformations have been developed desyl chloride and benzyl chloride as the oxidants (Table 1).
during the past decades.2 For primary alcohols, most attention is
Various benzylic alcohols were tested in the palladium catalysed
focused on the selective conversion of alcohols to the corresponding alcohol oxidation by using desyl Cl or BnCl as the oxidant (Table 1).
aldehydes, which includes classic processes using a stoichiometric By using desyl Cl as the oxidant, electron-rich and electron-neutral
amount of organic or inorganic oxidants3 as well as modern catalytic benzylic alcohols were selectively converted into the corresponding
processes in the presence of palladium catalysts.4 The direct oxida- aldehydes without any observation of esters (entries 1, 3 and 5).
tion of primary alcohols to the corresponding esters is also a However, when a weakly electron-withdrawing group was used in
potential approach and recently, several studies have been reported the case of p-Cl substituted benzylic alcohol, trace amounts of ester
on this topic.5 In many cases, the selective formation of a single and 70% aldehyde were observed (entry 7). Upon changing the
product such as an aldehyde, acid or ester is sometimes proble- substituent to a strongly electron-withdrawing group (p-CF3), the
matic, as mixtures of these products are usually unavoidable, which ester became the main product with only 20% of aldehyde form-
makes these processes both unpractical and less applicable.
ation (entry 9). When using BnCl as the oxidant, all of the benzylic
Up to now, little has been known about the factors that control alcohols were selectively converted to the corresponding esters
the selectivity between aldehyde formation and esterification in the (entries 4, 6, 8, and 10), except for the electron-donating p-OMe
presence of a palladium catalyst.5b Herein, we demonstrate an substituted benzylic alcohol, which afforded 26% of the aldehyde
oxidant controlled selective alcohol oxidation and uncover factors (entry 2). These results indicate that desyl Cl is suitable for aldehyde
that affect the selectivity between aldehyde formation and direct formation, while the aldehyde/ester selectivity is sensitive to the
esterification (Scheme 1).
electronic property of the substrates. Contrary to this, BnCl is suit-
Recently, our group demonstrated a Pd-catalysed selective and able for ester formation, including both electron-rich and electron-
general oxidative esterification of aldehyde with alcohol. Benzyl poor substituted substrates. Furthermore, esters were selectively
chloride was used as the oxidant, which could provide a covalently formed by using either desyl Cl or BnCl as the oxidant, when an ali-
phatic primary alcohol was used as the substrate (entries 11 and 12).
a College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072,
P. R. China. E-mail: aiwenlei@whu.edu.cn; Fax: +86-27-68754672;
Tel: +86-27-68754672
b State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute
of Chemical Physics, Chinese Academy of Sciences, 730000, Lanzhou, P. R. China
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c2cc38086b
The above results indicate that the electronic property of the
substrates is one of the important factors in controlling the
aldehyde/ester selectivity in primary alcohol oxidation when
using desyl Cl as the oxidant. This is consistent with reported
results involving aryl halides or O2 as the oxidant.5b,7 Moreover,
the structural properties of the primary alcohol are also impor-
tant, as the aliphatic alcohols tend to form esters compared to
‡ These authors contributed equally to this work.
c
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Table 1 Oxidant-controlled selective alcohol oxidationa
alkoxy palladium intermediate, I-2. The direct beta-hydride elimina-
tion affords the aldehyde and the palladium hydride intermediate
I-4 which then undergoes reductive elimination to regenerate the
Pd(0) species (Path a). This will result in selective aldehyde for-
mation. Further reaction of the resulting aldehyde with I-2 will
generate the hemiacetal palladium intermediate I-3 from which
beta-hydride elimination will release the ester and the Pd–H inter-
mediate I-4. Overall, this will result in the oxidative esterification of
primary alcohols.
Yieldb (%)
Entry
1
Oxidant
2
3
(1)
(2)
1
2
77 (2a)
26 (2a)
n.d. (3a)
57 (3a)
A
B
A
B
3
4
84 (2b)
n.d. (2b)
n.d. (3b)
97c (3b)
5
6
A
B
73 (2c)
n.d. (2c)
n.d. (3c)
96 (3c)
Both desyl Cl and BnCl are alkyl halides; however, the selectivity
of these two systems was found to be very different. This is ascribed
to the essential alcoholysis step of the oxidative addition inter-
mediate I-1. It has been shown that the alcoholysis occurs at the
Pd–Cl bond of the benzyl chloride system,9 in which the benzyl
group is preserved (X = Bn) (eqn (1)), and the alcoholysis occurs at
the Pd–enolate bond of the desyl chloride system, in which the
Pd–Cl bond is preserved (X = Cl, eqn (2)).10 These findings were
proved by using isotopic labelling experiments (Scheme 3). As the
deuterated benzylic alcohol was selectively converted to the corres-
ponding aldehyde by using desyl chloride as the oxidant, the C–Cl
bond of desyl chloride was selectively protonated, which indicates
that the alcoholysis step occurred at the Pd–enolate bond (X–Y =
Cl–enolate, Scheme 2). In contrast, the deuterated benzylic alcohol
was selectively converted (with 50% conversion) to the corres-
ponding ester by using m-OMe–BnCl as the oxidant and the C–Cl
bond was selectively deuterated, which showed that the alcoholysis
step occurred at the Pd–Cl bond (X–Y = Bn–Cl, Scheme 2).
When using desyl chloride as the oxidant, aldehyde formation was
favoured, compared to ester formation (Scheme 2, X–Y = Cl–enolate).
However, when the substituent on the benzylic alcohols changed to
an electron-withdrawing group, the ester was the major product
(Table 1, entry 9). We assume that this phenomenon is ascribed to
the activation of the aldehyde carbonyl group. As aldehyde was
generated in the reaction system, the electron-withdrawing group
activates the corresponding carbonyl group and makes it more
electron-deficient, thus the carbonyl group can easily form a hemi-
acetal (eqn (3)), followed by palladium-catalysed b-hydride elimination
to form the ester. Moreover, the stronger the electron-withdrawing
group, the easier the ester formation, which agrees with the results
7
8
A
B
70 (2d)
n.d. (2d)
Trace (3d)
88c (3d)
9
10
A
B
20 (2e)
n.d. (2e)
42 (3e)
75c (3e)
11
12
A
B
n.d. (2f)
n.d. (2f)
56 (3f)
75 (3f)
a
Reaction conditions: 1 (0.50 mmol), PdCl2(PPh3)2 (0.025 mmol), K2CO3
(0.50 mmol), A or B (0.50 mmol) in 2 mL of THF at 65–70 1C for 20 h. b Yields
were determined by GC analysis. n.d. = not detected. c Isolated yields.
benzylic alcohols, which could help explain why selective
aliphatic aldehyde formation is challenging.7,8 Then, for selective
esterification, the oxidant benzyl chloride is essential, as we have
tested many other oxidants as a comparison, such as non-benzylic
alkyl chloride, aryl halides, O2 and other a-halocarbonyls (see ESI,†
Table S1). All of these oxidants selectively provided benzaldehyde
from the oxidation of benzyl alcohol.
The palladium catalysed alcohol oxidation was assumed to be as
presented in the catalytic cycles shown in Scheme 2. First, the
oxidative addition of oxidant X–Y to Pd(0) generates intermediate
X–Pd(II)–Y (I-1). With the aid of a base, the following alcoholysis step
selectively occurs at the Pd–Y bond of I-1 with alcohol to generate an
Scheme 2 Two pathways of Pd-catalysed alcohol oxidation.
Scheme 3 Isotopic labelling experiments.
c
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listed in Table 1. For the aliphatic alcohol, there is no p–p conjugation such as p-COOMe also gave the corresponding esters in a high yield
from the carbonyl of the intermediate aldehyde; hence addition of (entry 2). Benzylic alcohols bearing meta-substituents, such as m-Me or
alcohol to the carbonyl of the corresponding aliphatic aldehyde is m-OMe (entries 3 and 4), afforded their corresponding esters in good
facile. Therefore, selective esterification was observed by using desyl Cl yields. The ortho-C–Cl bond was well tolerated and the ester product
as the oxidant.
was obtained in an excellent yield. The steric hindrance did not have
any negative effect on the yield (entry 6). It is worth noting that other
aromatic arenes such as thiophene-2-methanol could also be applied
in this oxidative esterification and gave the corresponding esters in a
good yield (entry 7). Moreover, alkyl alcohol is more suitable for
oxidative esterification, which has been shown in other reaction
systems. We subjected an alkyl alcohol to these oxidative conditions
and quantitative amounts of the desired ester were obtained (entry 8).
We have demonstrated an oxidant controlled palladium catalysed
selective oxidation of primary alcohols to aldehydes or esters. The
electronic properties of benzylic alcohols and the structure of the
oxidant are the important factors that control the selectivity between
aldehydes and esters. Electron-withdrawing groups promote the ester
formation by using desyl chloride as the oxidant. The covalent benzyl
ligand, derived from BnCl, is the key for the selective oxidative
esterification of primary alcohols. The Z3 coordination of benzyl
group to palladium might be essential for the ester formation.
This work was supported by the 973 Program (2012CB725302),
the National Natural Science Foundation of China (21025206 and
21272180) and the China Postdoctoral Science Foundation funded
project (2012M521458). We thank Dr Andrew G. Crawford for his
help in revising the manuscript.
(3)
Comparing BnCl with desyl chloride and the oxidants in
Table S1 (ESI†), it was found that the Bn–Pd moiety (X = Bn,
Scheme 2) is essential to the selective oxidative esterification, as
the Bn group could be considered as a covalent carbon anion
ligand which could easily form Z3 coordination to palladium
(eqn (1)).11 This Z3 coordination might facilitate the facile
dissociation of PPh3 and will favour the coordination of alde-
hyde to the palladium centre. This claim could be proved by
using a rigid bidentate dppf ligand in the reaction system,
which resulted in a worse selectivity (see ESI,† Table S2).
Compared with selective aldehyde formation by using desyl
Cl as the oxidant, the selective oxidative esterification of
primary alcohols is more interesting when BnCl is used as
the oxidant. Previously, very few examples have demonstrated
the selective formation of esters directly from the alcohol in the
presence of a palladium catalyst.5 Moreover, benzyl chloride is
a fundamental industrial chemical, which is cheap and easily
obtained. The side product toluene is a widely used organic
solvent and can easily be removed. There is strong potential to
use benzyl Cl as the oxidant in both academia and industry.
Therefore, further application of BnCl in the palladium catalysed
oxidative esterification of more primary alcohols was investigated
(Table 2). p-F substituted benzyl alcohol gave excellent yields of the
corresponding ester (entry 1). Strong electron-withdrawing groups
Notes and references
1 R. A. Sheldon and J. K. Kochi, Metal-catalyzed oxidations of organic
compounds: mechanistic principles and synthetic methodology including
biochemical processes, Academic Press, New York, 1981.
2 (a) M. S. Sigman and D. R. Jensen, Acc. Chem. Res., 2006, 39, 221–229;
(b) R. A. Sheldon, I. W. C. E. Arends, G.-J. ten Brink and A. Dijksman,
Acc. Chem. Res., 2002, 35, 774–781; (c) J. Muzart, Tetrahedron, 2003, 59,
5789–5816; (d) M. J. Schultz and M. S. Sigman, Tetrahedron, 2006, 62,
8227–8241; (e) S. S. Stahl, Angew. Chem., Int. Ed., 2004, 43, 3400–3420;
( f ) W. Kroutil, H. Mang, K. Edegger and K. Faber, Adv. Synth. Catal.,
2004, 346, 125–142; (g) T. Mallat and A. Baiker, Chem. Rev., 2004, 104,
3037–3058; (h) S. Krishnan, J. T. Bagdanoff, D. C. Ebner, Y. K.
Ramtohul, U. K. Tambar and B. M. Stoltz, J. Am. Chem. Soc., 2008,
130, 13745–13754; (i) T. Nishimura, T. Onoue, K. Ohe and S. Uemura,
J. Org. Chem., 1999, 64, 6750–6755.
Table 2 Pd-catalysed selective oxidative esterification of primary alcoholsa
3 G. Cainelli and G. Cardillo, Chromium oxidations in organic
chemistry, Springer-Verlag, Berlin, New York, 1984.
Entry
Product
3
Yieldb (%)
4 M. Beller and C. Bolm, Transition metals for organic synthesis:
building blocks and fine chemicals, WILEY-VCH, Weinheim, 2nd
rev. and enl. edn, 2004.
1
2
R0 = F
3g
3h
91
78
R0 = COOMe
5 (a) S. Gowrisankar, H. Neumann and M. Beller, Angew. Chem., Int.
Ed., 2011, 50, 5139–5143; (b) C. Liu, J. Wang, L. Meng, Y. Deng, Y. Li
and A. Lei, Angew. Chem., Int. Ed., 2011, 50, 5144–5148; (c) D. Zhang
and C. Pan, Catal. Commun., 2012, 20, 41–45; (d) F. Luo, C. Pan,
J. Cheng and F. Chen, Tetrahedron, 2011, 67, 5878–5882.
6 C. Liu, S. Tang, L. Zheng, D. Liu, H. Zhang and A. Lei, Angew. Chem.,
Int. Ed., 2012, 51, 5662–5666.
R0 = Me
3i
3j
89
80
3
4
R0 = OMe
5c
R0 = Me
R0 = Cl
3k
3l
>99
94
6d
7 Y. Tamaru, Y. Yamada, K. Inoue, Y. Yamamoto and Z. Yoshida,
J. Org. Chem., 1983, 48, 1286–1292.
8 R. Liu, X. Liang, C. Dong and X. Hu, J. Am. Chem. Soc., 2004, 126,
4112–4113.
9 S. L. Marquard and J. F. Hartwig, Angew. Chem., Int. Ed., 2011, 50,
7119–7123.
10 M. A. Zuideveld, P. C. J. Kamer, P. W. N. M. van Leeuwen, P. A. A.
Klusener, H. A. Stil and C. F. Roobeek, J. Am. Chem. Soc., 1998, 120,
7977–7978.
11 (a) P. Fitton, J. E. McKeon and B. C. Ream, Chem. Commun., 1969,
370–371; (b) R. Ros, M. Lenarda, T. Boschi and R. Roulet, Inorg.
Chim. Acta, 1977, 25, 61–64.
7
3m
3n
83
8c
>99
a
Reaction conditions: 1 (0.50 mmol), PdCl2(PPh3)2 (0.025 mmol),
K2CO3 (0.50 mmol), BnCl (0.50 mmol) in 2 mL of THF at 65–70 1C for
b
c
d
20 h. Isolated yields. 1.0 mmol scale. 30 h.
c
1326 Chem. Commun., 2013, 49, 1324--1326
This journal is The Royal Society of Chemistry 2013