Alkenes from alcohols by tandem hydrogen transfer and condensation

Article abstract of DOI:10.1002/adsc.200800338

A ruthenium-catalysed oxidation of alcohols by hydrogen transfer has been coupled with organocatalysed condensations using pyrrolidine or piperidine, to give α,β-unsaturated esters and nitroalkenes. Reactions proceed with high (E)-selectivity and provide an efficient and straightforward route to α,β-unsaturated compounds.

Full text of DOI:10.1002/adsc.200800338

COMMUNICATIONS
DOI: 10.1002/adsc.200800338
Alkenes from Alcohols by Tandem Hydrogen Transfer and
Condensation
Michael I. Hall,a Simon J. Pridmore,a and Jonathan M. J. Williamsa,*
a
Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, U.K.
Fax/Phone: (+44)-(0)1225-38-62-31
E-mail: J.M.J.Williams@bath.ac.uk
Received: June 2, 2008; Published online: August 13, 2008
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800338.
Abstract: A ruthenium-catalysed oxidation of alco-
hols by hydrogen transfer has been coupled with or-
ganocatalysed condensations using pyrrolidine or
piperidine, to give a,b-unsaturated esters and nitro-
alkenes. Reactions proceed with high (E)-selectivity
and provide an efficient and straightforward route
to a,b-unsaturated compounds.
Keywords: alcohols; alkenes; hydrogen transfer; or-
ganocatalysis; ruthenium
Scheme 1. Tandem oxidation/alkene formation.
We have recently reported that crotononitrile is a
useful hydrogen acceptor in the ruthenium-catalysed and their salts.[9] These reactions were catalysed by
oxidation of alcohols to methyl esters.[1] Various DMAP or pyrrolidine. We were intrigued by the pos-
ruthenium catalysts have also been used by us[2] and sibility of combining these organocatalytic reactions
by others[3] to allowalcohols to be used as alkylating
with ruthenium-catalysed hydrogen transfer reactions.
agents in a sequence involving temporary removal of A model reaction involving the conversion of benzyl
hydrogen from an alcohol to give an aldehyde which alcohol 1 and malonic half ester 2 into alkene 3 was
undergoes in situ alkene formation followed by return chosen, using crotononitrile as the hydrogen acceptor
[4,5]
À
of the hydrogen to provide a newC C bond.
We (Scheme 2). We have previously found that the com-
were interested in the possibility of intercepting this bination of Ru
ACHTREUNG
pathway by transferring hydrogen to a suitable ac- useful for hydrogen-transfer processes and chose to
ceptor providing a route for the conversion of alco- use this as the catalyst.[11] The use of triethylamine or
hols into alkenes, as shown in Scheme 1.
dimethylaminopyridine as the base/organocatalyst led
In order for this approach to be successful, the hy- to a lowconversion into product (16% and 13%) with
drogen acceptor must be able to accept hydrogen the major product being benzaldehyde (59% and
much more readily than the alkene which is being
generated, and the alkene-forming reaction must not
interfere with the hydrogen-transfer catalysis. Exam-
ples of other approaches to the conversion of alcohols
into alkenes include oxidation with manganese diox-
ide and in situ Wittig reaction,[6] along with sequential
Swern/Wittig[7] and TPAP/Wittig processes.[8]
List and co-workers have recently reported the con-
version of aldehydes into unsaturated esters using a
decarboxylative condensation of malonate half esters Scheme 2. Alkene formation from benzyl alcohol 1.
Adv. Synth. Catal. 2008, 350, 1975 – 1978
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1975

Michael I. Hall et al.
COMMUNICATIONS
56%). Pyrrolidine and piperidine were both successful with good isolated yields. The carboxylate salts could
as co-catalysts, with both giving complete consump- be be used in place of the half esters (entries 1 and 3),
tion of starting material after 2 h at reflux using 2.5 with the addition of acetic acid. The carboxylate salts
mol% catalyst. The use of pyrrolidine afforded prod- of malonate half esters are often cheaper than the
uct with a trace (<3%) of benzaldehyde, whereas acids, and are readily prepared from the diesters by
with piperidine, more aldehyde was present (18%).
We then applied these conditions to the formation
treatment with base.[11]
A variety of substituents could be attached to the
of a range of alkenes, as shown in Table 1. Methyl, starting benzyl alcohol including halides (entries 6–8),
ethyl, benzyl and tert-butyl esters were all formed electron-donating groups (entries 9 and 10) and elec-
tron-withdrawing groups (entry 11) along with the
ortho-substituted product formed in entry 12. Aliphat-
ic alcohols led to mixtures of a,b- and b,g-alkene re-
gioisomers, as expected from the corresponding direct
reactions of malonate half-esters with aliphatic alde-
hydes.
Table 1. Alkenes formed by tandem oxidation/decarboxyla-
tive condensation.
As an alternative to the decarboxylative alkene for-
mation using malonate half esters, we chose to inves-
tigate the use of nitroalkanes in a tandem alcohol oxi-
dation/nitroaldol condensation process. Nitroalkenes
are useful precursors to a range of other functional
groups including aldehydes, ketones and amines.[13]
Alcohol 4 and nitroethane 5 were chosen as model
Entry
Alkene product
Yield [%][a]
1
2
3
4
5
74[b]
95
71[b]
substrates for the formation of nitroalkene
6
(Scheme 3). The use of triethylamine, dimethylamino-
84
71
6
87
90
74
71
83
74
73
Scheme 3. Tandem oxidation/nitroaldol reaction.
7
pyridine, pyrrolidine or piperidine led to unreactive
systems (a small amount of aldehyde was formed in
some cases, but essentially no alkene product). How-
ever, the use of piperidinium acetate as co-catalyst
provided 100% conversion in the formation of (E)-
alkene 6.
8
9
These conditions were then applied to the synthesis
of other nitroalkenes (Table 2). Whilst nitroethane
was used in most cases, nitromethane was also used
successfully (entry 1). The tolyl alcohol 4 and its
ortho-substituted analogue afforded product cleanly
(entries 2 and 3). Small amounts of aldehyde were
present in some of the other examples, but the prod-
ucts were readily isolated by column chromatography.
Furfuryl alcohol was converted cleanly into product,
but there was some decompostion during chromatog-
raphy.
Finally, we have also applied this oxidation/conden-
sation chemistry to the reaction of alcohol 4 with keto
nitrile 7 to give the alkene 8 with 100% conversion
(Scheme 4). Only one isomer of product was observed
by NMR spectroscopy, and an nOe experiment re-
10
11
12
[a]
All reactions had reached full conversion as determined
by analysis of the H NMR spectrum of the crude materi-
1
al which showed only the presence of the (E)-isomer of
alkene. Products were purified by column chromatogra-
phy.
The potassium carboxylate salt of the malonate half ester
was used, with 1.5 equiv acetic acid.
[b]
1976
asc.wiley-vch.de
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2008, 350, 1975 – 1978

Alkenes from Alcohols by Tandem Hydrogen Transfer and Condensation
COMMUNICATIONS
Table 2. Nitroalkenes formed by tandem oxidation/nitroal-
dol reaction.
In summary, we have used a combination of ruthe-
nium-catalysed hydrogen-transfer with organocata-
lysed alkene formation to provide newmethodology
for the conversion of alcohols into alkenes.
Experimental Section
Typical Procedure for the Tandem Oxidation/
Decarboxylation Reaction.
Entry
1
Alkene product
Yield [%][a]
[100][b]
To oven-dried, argon-purged Radleyꢁs carousel tubes con-
taining Ru(PPh3)3(CO)H2 (86 mg, 0.1 mmol, 0.025 equiv.),
A
AHCTREUNG
Xantphos (56 mg, 0.1 mmol, 0.025 equiv.) and pyrrolidine
(100 mL, 1.20 mmol, 0.30 equiv.) were added toluene (4 mL),
benzyl alcohol (436 mL, 4 mmol, 1 equiv.), crotononitrile
(488 mL, 6 mmol, 1.5 equiv.) and monoethyl malonate
(581 mL 4.4 mmol, 1.1 equiv.). The reactions were heated to
reflux for 2 h, cooled to room temperature and the solvent
was removed under vacuum. The resultant oil was purified
by column chromatography [9:1 petroleum ether (b.p. 40–
608C)/diethyl ether, Rf =0.31]. (E)-Ethyl cinnamate was ob-
tained as a clear oil; yield: 679.5 mg (95%). 1H NMR
(300 MHz, CDCl3): d=7.70 (d, 1H, J=15.9 Hz), 7.55–7.36
(m, 5H), 6.45 (d, 1H, J=15.9 Hz), 4.27 (q, 2H, J=7.2 Hz),
1.35 (t, 3H, J=7.2 Hz); 13C NMR (75.5 MHz, CDCl3): d=
166.9, 144.5, 130.1, 128.8, 127.9, 118.2, 60.4, 14.2.
2
3
4
84[c]
83
73
5
6
7
62
Typical Procedure for the Tandem Oxidation/
Nitroaldol Reaction.
73[c]
67
To oven-dried, argon-purged Radleyꢁs carousel tubes con-
taining
Ru
A
(114.5 mg,
0.125 mmol,
0.025 equiv.), Xantphos (72.5 mg, 0.125 mmol, 0.025 equiv.)
and piperidinium acetate (181 mg, 1.25 mmol, 0.25 equiv.)
were added toluene (5 mL), para-methylbenzyl alcohol
(611 mg, 5 mmol, 1 equiv.), crotononitrile (610 mL, 7.5 mmol,
1.5 equiv.) and nitroethane (465 mL, 6.5 mmol, 1.3 equiv.).
The reaction mixtures were heated to reflux for 8 h, cooled
to room temperature and the solvent was removed under
vacuum. The resulting oil was purified by column chroma-
tography [9:1 petroleum ether (b.p. 40–608C)/diethyl ether,
Rf =0.40], affording (E)-1-methyl-4-(2-nitroprop-1-enyl)ben-
zene as a pale yellowsolid; yield: 744 mg (84%) 1H NMR
(300 MHz, CDCl3, 258C): d=8.09 (s, 1H, CH), 7.36 (d, 2H,
J=8.1 Hz), 7.28 (d, 2H, J=8.1 Hz), 2.47 (d, 3H, J=0.9 Hz),
2.42 (s, 3H); 13C NMR (75.5 MHz, CDCl3, 258C): d=146.9,
140.5, 133.7, 130.1, 129.6, 129.4, 21.4, 14.1.
8
N
[a]
1
tography.
Conversion.
[b]
[c]
Acknowledgements
We wish to thank the EPSRC for studentship funding(to
MIH and SJP) through the Doctoral Training Account.
Scheme 4. Tandem oxidation/Knoevenagel condensation.
References
vealed an enhancement of the alkenyl signal upon ir-
radiation of the tert-butyl group, indicating the forma-
tion of the (E)-isomer of product.
[1] N. A. Owston, A. J. Parker, J. M. J. Williams, Chem.
Commun. 2008, 624.
Adv. Synth. Catal. 2008, 350, 1975 – 1978
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1977

Michael I. Hall et al.
COMMUNICATIONS
[2] a) M. G. Edwards, R. F. R. Jazzar, B. M. Paine, D. J.
Shermer, M. K. Whittlesey, J. M. J. Williams, D. D.
Edney, Chem. Commun. 2004, 90; b) P. A. Slatford,
M. K. Whittlesey, J. M. J. Williams, Tetrahedron Lett.
2006, 47, 6787; c) S. Burling, B. M. Paine, D. Nama,
V. S. Brown, M. F. Mahon, T. J. Prior, P. S. Pregosin,
M. K. Whittlesey, J. M. J. Williams, J. Am. Chem. Soc.
2007, 129, 1987.
[3] For representative examples, see; a) R. Grigg, T. R. B.
Mitchell, S. Sutthivaiyakit, N. Tongpenyai Tetrahedron
Lett. 1981, 22, 4107; b) C. S. Cho, B. T. Kim, T. J. Kim,
S. C. Shim, J. Org. Chem. 2001, 66, 9020; c) R. Martí-
nez, D. J. Ramón, M. Yus, Tetrahedron 2006, 62, 8982;
d) R. Martínez, D. J. Ramón, M. Yus, Tetrahedron
2006, 62, 8988.
[5] For a reviewof the borrowing hydrogen approach to
using alcohols as alkylating agents, see; a) M. H. S. A.
Hamid, P. A. Slatford, J. M. J. Williams, Adv. Synth.
Catal. 2007, 349, 1555; b) G. Guillena, D. J. Ramón, M.
Yus, Angew. Chem. Int. Ed. 2007, 46, 2358.
[6] R. J. K. Taylor, M. Reid, J. Foot, S. A. Raw, Acc. Chem.
Res. 2005, 38, 851.
[7] R. E. Ireland, D. W. Norbeck, J. Org. Chem. 1985, 50,
2198.
[8] R. N. MacCoss, E. P. Balskus, S. V. Ley, Tetrahedron
Lett. 2003, 44, 7779.
[9] B. List, A. Doehring, M. T. Hechavarria Fonesca, A.
Job, R. Rios Torres, Tetrahedron 2006, 62, 476.
[10] M. Kranenburg, Y. E. M. van der Burgt, P. C. J. Kamer,
P. W. N. M. van Leeuwen, Organometallics 1995, 14,
3081.
[4] Other catalysts, especially Ir complexes are also suc-
[11] a) N. J. Wise, J. M. J. Williams, Tetrahedron Lett. 2007,
48, 3639; b) S. J. Pridmore, P. A. Slatford, J. M. J. Wil-
liams, Tetrahedron Lett. 2007, 48, 5111; c) S. J. Prid-
more, P. A. Slatford, A. Daniel, M. K. Whittlesey,
J. M. J. Williams, Tetrahedron Lett. 2007, 48, 5115; d) N.
Anand, N. A. Owston, A. J. Parker, P. A. Slatford,
J. M. J. Williams, Tetrahedron Lett. 2007, 48, 7761.
[12] For example, see: M. E. Hediger Bioorg. Med. Chem.
2004, 12, 4995.
À
cessful for C C bond formation from alcohols, for ex-
amples, see: a) M. G. Edwards, J. M. J. Williams,
Angew. Chem. Int. Ed. 2002, 41, 4740; b) K. Taguchi, Y.
Ishii, J. Am. Chem. Soc. 2004, 126, 72; c) C. Lçfberg, R.
Grigg, A. Keep, A. Derrick, V. Sridharan, C. Kilner,
Chem. Commun. 2006, 5000; d) C. Lçfberg, R. Grigg,
M. A. Whittaker, A. Keep, A. Derrick, J. Org. Chem.
2006, 71, 8023; for
a Pd-catalysed example, see:
e) M. S. Kwon, N. Kim, S. H. Seo, I. S. Park, R. K.
Cheedrala, J. Park, Angew. Chem. Int. Ed. 2005, 44,
6913.
[13] For example, see: G. W. Kabalka, L. H. M. Guindi,
R. S. Varma, Tetrahedron 1990, 46, 7443, and references
cited therein.
1978
asc.wiley-vch.de
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2008, 350, 1975 – 1978