Oxidation of primary alcohols to methyl esters by hydrogen transfer

Article abstract of DOI:10.1039/b717073d

The oxidation of alcohols in the presence of methanol has been achieved using a ruthenium catalyst with crotononitrile as the hydrogen acceptor. The Royal Society of Chemistry.

Full text of DOI:10.1039/b717073d

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Oxidation of primary alcohols to methyl esters by hydrogen transfer{
a
Nathan A. Owston, Alexandra J. Parker and Jonathan M. J. Williams*
b
a
Received (in Cambridge, UK) 5th November 2007, Accepted 26th November 2007
First published as an Advance Article on the web 6th December 2007
DOI: 10.1039/b717073d
The oxidation of alcohols in the presence of methanol has been
achieved using a ruthenium catalyst with crotononitrile as the
hydrogen acceptor.
processes which involve the transfer of hydrogen from an alcohol
9
to an alkene or alkyne.
10
In preliminary experiments, we wished to identify a suitable
alkene as the hydrogen acceptor, and chose to examine the
oxidation of benzyl alcohol to benzaldehyde using 2.5 mol%
The oxidative dimerisation of primary alcohols to give esters has
1
been reported using hydrogen transfer reactions and with
2
acceptorless dehydrogenation. In this chemistry, an alcohol is
11
Ru(PPh ) (CO)H with 2.5 mol% Xantphos as shown in
3
3
2
Scheme 2. a,b-Unsaturated nitriles were found to be effective for
this transformation, while simple alkenes and alkynes including
1-hexene, styrene, trimethylvinylsilane, methyl acrylate, 1-hexyne
and phenylacetylene all gave less than 5% conversion under these
conditions. Whilst the more electron deficient alkenes 4 and 5 gave
a greater conversion within 2 h (95% and 67% respectively),
crotononitrile 3 was chosen as the most suitable alkene due to the
volatility of this alkene and its reduced product.
initially oxidised to an aldehyde which reacts reversibly with more
alcohol to form a hemiacetal and further oxidation leads to the
formation of the ester. Related to this process is the conversion of
3
diols into lactones. The metal-catalysed Tishchenko dimerisation
4
reaction of aldehydes to give esters is also well-known.
However, the reaction of two alcohols to give an ester by
oxidative coupling is more problematic due to the potential
formation of a mixture of products. The conversion of activated
alcohols, such as cinnamyl alcohol, into methyl esters has been
Using methanol as a cosolvent led to the formation of methyl
esters from a range of alcohols (Scheme 3, Table 1). After some
optimisation, it was found that allowing complexation between
5 mol% Ru(PPh ) (CO)H and 5 mol% Xantphos for 1 h,
5,6
reported using manganese dioxide with cyanide, which is capable
of oxidising the cinnamyl alcohol and intermediate cyanohydrin,
but not methanol. A similar strategy has been employed using
3
3
2
followed by 24 h at 110 uC in a methanol–toluene (1 : 1) solution in
the presence of 3 equivalents of crotononitrile 3 was suitable for
the oxidation of most alcohols. The addition of a small amount of
water was also found to be beneficial.
7
iodosobenzene as the oxidant.
We were interested in the possibility of using metal catalysed
hydrogen transfer processes to effect the oxidation of alcohols to
methyl esters according to Scheme 1. Methanol is harder to oxidise
than most primary alcohols due to the high oxidation potential
The majority of alcohols underwent clean transformation into
the corresponding esters with essentially complete conversion, and
were isolated in good yields. There were three alcohols where
incomplete conversion was observed under these conditions; these
were the sterically most hindered substrates: benzyl alcohol,
p-nitrobenzyl alcohol and cyclohexylmethanol. Benzylic alcohols
would normally be expected to undergo oxidation more readily
8
of methanal, and by using methanol as solvent, we hoped to be
able to form methyl esters selectively. We chose to use an alkene
as the hydrogen acceptor, although the use of a ketone as
the hydrogen acceptor or acceptorless dehydrogenation are also
potentially viable approaches. We have recently reported the use
3 3 2
of Ru(PPh ) (CO)H with the bidentate ligand Xantphos for
Scheme 1 Oxidation of primary alcohols to methyl esters.
Scheme 2 Alkenes as hydrogen acceptors for alcohol oxidation.
a
Department of Chemistry, University of Bath, Claverton Down, Bath,
UKBA2 7AY. E-mail: j.m.j.williams@bath.ac.uk; Fax: +441225386231;
Tel: +44 1225 383942
AstraZeneca, Global Process R&D, Avlon Works, Severn Road,
b
Hallen, Bristol, UK BS10 7ZE.
E-mail: alexandra.parker@astrazeneca.com
{ Electronic supplementary information (ESI) available: Experimental
procedures and spectroscopic data. See DOI: 10.1039/b717073d
Scheme 3 Reaction conditions for methyl ester formation.
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24 | Chem. Commun., 2008, 624–625

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Table 1 Conversion of alcohols into methyl esters
a
Alcohol
Methyl ester
Yield (%)
b
8
7
3
9
Scheme 4 Oxidation of octanal to the methyl ester.
In all cases, small quantities of the product arising from con-
jugate addition of methanol to crotononitrile, MeCH(OMe)
8
8
4
7
2
CH CN, were observed. This byproduct was readily removed by
column chromatography or by evaporation under high vacuum.
The reaction was also applied to the conversion of octanal into
its methyl ester (Scheme 4). Murahashi has previously reported the
reaction of octanal with methanol in the presence of mesityl oxide
c
(
70)
7
7
4
6
as the hydrogen acceptor, which gave 66% methyl octanoate after
1
4
days at 140 uC using 10 mol% Ru(PPh ) H .
3
4
2
In summary, primary alcohols have been oxidised to the
corresponding methyl esters in good isolated yields using a
ruthenium catalysed hydrogen transfer process.
We thank the EPSRC and AstraZeneca for funding a student-
ship (to N.A.O.).
8
8
6
4
d
c
(
76)
Notes and references
1
S.-I. Murahashi, T. Naota, K. Ito, Y. Maeda and H. Taki, J. Org.
Chem., 1987, 52, 4319.
J. Zhang, G. Leitus, Y. Ben-David and D. Milstein, J. Am. Chem. Soc.,
c
(
.95)
2
2005, 127, 10840. An extension of this work to the formation of amides
from alcohols and amines has also recently been reported:
C. Gunanathan, Y. Ben-David and D. Milstein, Science, 2007, 317, 790.
J. Zhao and J. F. Hartwig, Organometallics, 2005, 24, 2441; Y. R. Lin,
X. C. Zhu and Y. F. Zhou, J. Organomet. Chem., 1992, 429, 269;
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3
4
a
2361; H. C. Maytum, B. Tavassoli and J. M. J. Williams, Org. Lett.,
Isolated yield after purification by column chromatography, except
where indicated. 48 h. Conversion. 36 h.
b
c
d
2007, 9, 4387.
For representative examples, see: T. Suzuki, T. Yamada, T. Matsuo,
K. Watanabe and T. Kadoh, Synlett, 2005, 1450; T. Suzuki, T. Yamada,
K. Watanabe and T. Katoh, Bioorg. Med. Chem. Lett., 2005, 15, 2583;
T. Ooi, K. Ohmatsu, K. Sasaki, T. Miura and K. Maruoka,
Tetrahedron Lett., 2003, 44, 3191.
than aliphatic alcohols, and we wondered whether a disfavourable
hemiacetal formation from the intermediate aldehyde was
responsible for the lower conversion. However, both unreacted
benzyl alcohol and benzaldehyde (y1 : 1) were present in the
crude product, suggesting that both initial oxidation and
hemiacetal formation were disfavoured relative to the aliphatic
examples. In the cases of p-nitrobenzyl alcohol and cyclohexyl-
methanol, conversions of 84% and 76% were observed, with no
5
6
J. S. Foot, H. Kanno, G. M. P. Giblin and R. J. K. Taylor, Synthesis,
2
003, 1055.
E. J. Corey, N. W. Gilman and B. E. Ganem, J. Am. Chem. Soc., 1968,
0, 5616.
9
7 H. Tohma, T. Maegawa and Y. Kita, Synlett, 2003, 723 and references
therein.
H. Adkins, R. M. Elofson, A. G. Rossow and C. C. Robinson, J. Am.
Chem. Soc., 1949, 71, 3622.
9 P. A. Slatford, M. K. Whittlesey and J. M. J. Williams, Tetrahedron
Lett., 2006, 47, 6787.
0 S. J. Pridmore, P. A. Slatford and J. M. J. Williams, Tetrahedron Lett.,
2007, 48, 5111; S. J. Pridmore, P. A. Slatford, A. Daniel, M. K.
8
1
intermediate aldehyde detected in the H NMR spectrum of the
crude product.
1
We were pleased to note that the alkene-containing alcohols
cinnamyl alcohol and citronellol underwent oxidation without
reduction or isomerisation of the alkene.
Whittlesey and J. M. J. Williams, Tetrahedron Lett., 2007, 48, 5115.
11 Z. Freixa and P. W. N. M. van Leeuwen, Dalton Trans., 2003, 1890.
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