1, 4-butanediol as a reducing agent in transfer hydrogenation reactions

Article abstract of DOI:10.1002/asia.200900527

1, 4-Butanediol is able to deliver two equivalents of H₂ in hydrogen- transfer reactions to ketones, imines, and alkenes. Unlike simple alcohols, which establish equilibrium in the reduction of ketones, 1, 4-butanediol acts essentially irreversibly owing to the formation of butyrolactone, which acts as a thermodynamic sink. It is therefore not necessary to use 1, 4- butanediol in great excess in order to achieve reduction reactions. In addition, allylic alcohols are reduced to saturated alcohols through an isomerization/ reduction sequence using a ruthenium catalyst with 1, 4-butanediol as the reducing agent. Imines and alkenes are also reduced under similar conditions.

Full text of DOI:10.1002/asia.200900527

FULL PAPERS
DOI: 10.1002/asia.200900527
1,4-Butanediol as a Reducing Agent in Transfer Hydrogenation Reactions
Hannah C. Maytum,[a] Javier Francos,[a] David J. Whatrup,[b] and
Jonathan M. J. Williams*[a]
Dedicated to the 150th anniversary of Japan–UK diplomatic relations
Abstract: 1,4-Butanediol is able to de-
liver two equivalents of H2 in hydro-
gen-transfer reactions to ketones,
imines, and alkenes. Unlike simple al-
cohols, which establish equilibrium in
the reduction of ketones, 1,4-butane-
diol acts essentially irreversibly owing
to the formation of butyrolactone,
which acts as a thermodynamic sink. It
is therefore not necessary to use 1,4-
butanediol in great excess in order to
achieve reduction reactions. In addi-
tion, allylic alcohols are reduced to sa-
turated alcohols through an isomeriza-
tion/reduction sequence using a ruthe-
nium catalyst with 1,4-butanediol as
the reducing agent. Imines and alkenes
are also reduced under similar condi-
tions.
Keywords: hydrogenation · isomer-
ization
· lactones · reduction ·
ruthenium
Introduction
Transition metals have been widely exploited for the reduc-
tion of unsaturated functional groups either by direct hydro-
genation with H2 or by transfer hydrogenation with a suita-
ble hydrogen donor.[1] The most commonly used hydrogen
donors used in ruthenium-catalyzed ketone reduction are
formic acid and isopropanol.[2,3] The use of alcohols as re-
ducing agents in transfer-hydrogenation reactions can lead
to the problem of reversibility, and a very large excess of
the alcohol may be required in order to drive the equilibri-
um. Therefore, in the reduction of ketone 1 to alcohol 2, iso-
propanol is used in large excess in order to approach full
conversion (Scheme 1). As the stability of ketone 1 increas-
es, it becomes more difficult to drive the reaction to comple-
tion.[4]
Scheme 1. Reversibility in hydrogen-transfer reactions.
(2 equivalents of H2 for MW=90.1 gmolÀ1) suggests that
the latter may be a useful alternative as a hydrogen donor.
In addition, 1,4-butanediol is now available from renewable
resources, making it an attractive choice of reagent.[5] How-
ever, the most significant advantage of 1,4-butanediol as a
reducing agent is the fact that it can act irreversibly. After
loss of hydrogen from 1,4-butanediol 3, the initially-formed
aldehyde 4 is trapped by the pendant alcohol to give lactol
5, which undergoes a second loss of hydrogen, leading to the
lactone 6 (Scheme 2). 1,4-Butanediol is therefore an alterna-
tive to formic acid as an irreversible reducing agent, and
may have advantages with catalysts that do not react via
metal hydrides.
Comparison of the available hydrogen in isopropanol (1
equivalent of H2 for MW=60.1 gmolÀ1) with 1,4-butanediol
[a] H. C. Maytum, J. Francos, Prof. J. M. J. Williams
Department of Chemistry
University of Bath
Claverton Down, Bath, BA2 7AY (UK)
Fax : (+44)1225-38-62-31
E-mail: j.m.j.williams@bath.ac.uk
[b] Dr. D. J. Whatrup
GlaxoSmithKline Research and Development
Old Powder Mills
Tonbridge, Kent, TN11 9AN (UK)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.200900527.
Scheme 2. Lactone formation when 1,4-butanediol is used as a hydrogen
donor.
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Chem. Asian J. 2010, 5, 538 – 542

Table 1. Aldehydes and ketones reduced by 1,4-butanediol.
There are other examples of the oxidation of diols to lac-
tones by either transfer hydrogenation[6] or dehydrogena-
tion[7] using ruthenium catalysts, although the only report of
using diols to reduce carbonyl compounds is our preliminary
communication.[8] We have also reported the use of levulinic
acid (4-oxopentanoic acid) as an oxidant in hydrogen-trans-
fer reactions, which also uses lactonization to drive the equi-
librium.[9]
Entry
Aldehyde/Ketone substrate 1
Conversion
into alcohol 2 [%][a,b]
1
2
3
4
100 (81)
100 (82)[c]
100 (87)
100 (60)
Results and Discussion
We have recently been using the combination of Ru-
ACHTUNGTRENNUNG(PPh3)3(CO)H2 with bidentate phosphines for hydrogen-
transfer reactions,[10] especially in reactions involving C C
À
À
and C N bond formation from alcohols using borrowing-hy-
5
100
drogen methodology.[11] Using 1,4-butanediol 3, preliminary
optimization studies led to the use of RuACHTUNGTRNEG(UN PPh3)3(CO)H2
6
7
8
9
100 (92)
90 (84)[c]
92 (88)[c]
98 (79)[c]
with the bidentate phosphine ligand DPEphos, (o-
Ph2PC6H4)2O, in toluene at reflux, and we applied the reac-
tion to the reduction of a range of ketones and aldehydes, as
shown in Table 1.[8]
We were pleased to find that aldehydes (entries 1–3) were
reduced to the corresponding primary alcohols with com-
plete conversion, and in good isolated yield. Ketones were
reduced under the same reaction conditions, and it is note-
worthy that even particularly stable ketones, such as 4-me-
thoxyacetophenone (entry 10) and tetralone (entry 11) were
reduced with good conversions. In some cases, isolated
yields were lower than anticipated, either arising from the
volatility (e.g., entry 4) or loss of material during isolation
by column chromatography.
10
11
87
91[c]
[a] Yields of isolated product are given in parentheses. [b] The carbonyl
compound (1 mmol) and 1,4-butanediol (1 mmol) were reacted with Ru-
Alternative diols were found to be less effective for the
reduction of propiophenone. Under conditions in which
96% conversion was achieved with 1,4-butanediol, only 9%
conversion was observed using 1,3-propanediol. 50% con-
version was achieved with 1,5-pentanediol and 26% conver-
sion with 1,6-hexanediol. Very recently, glycerol has been
used as a reducing agent in the ruthenium-catalyzed reduc-
tion of carbonyl compounds, in which it was used in excess
as the solvent.[12]
Our attention then turned to the reduction of allylic alco-
hols to saturated alcohols via an isomerization/reduction
pathway using 1,4-butanediol as the reducing agent. The re-
duction of allylic alcohols by this pathway has recently been
reported by Cadierno and Gimeno using isopropanol as the
solvent and reducing agent.[13] The reaction proceeds by iso-
merization of the allylic alcohol 7 into the ketone 8 followed
by ketone reduction to give the saturated alcohol 9, as
shown in Scheme 3.
ACHTUNGTRENNUNG
Using [RuACHTNUGTRNEUNG(p-cymene)Cl2]2 in combination with dppf af-
forded an active catalyst for this transformation. We then
applied this methodology to the reduction of a range of al-
lylic alcohols, detailed in Table 2. The isomerization/reduc-
tion was successfully achieved, and the isomerization was
significantly faster than the reduction, as reactions, which
were analyzed after an hour had undergone complete iso-
merization, but minimal reduction. Interestingly, the 4-
chloro substrate (entry 2) underwent loss of chloride, where-
as for the 3-chloro substrate (entry 3), it remained intact. In
the case of geraniol (entry 12), only the alkene of the allylic
alcohol was reduced. The propargylic alcohol (entry 13) was
also reduced to give a 76:24 ratio of the saturated alcohol
and cinnamyl alcohol. The a,b-unsaturated ketone
(entry 14) was reduced to the corresponding saturated alco-
hol.
Whilst it was experimentally convenient to run reactions
at a 1 mmol scale using an excess of 1,4-butanediol, we also
repeated the reduction of 1-phenyl-prop-2-en-1-ol (entry 1)
at a 10 mmol scale using only 0.5 equivalents of 1,4-butane-
diol. The reduced product was isolated in 74% yield.
Scheme 3. Tandem isomerization/reduction of allylic alcohols.
Chem. Asian J. 2010, 5, 538 – 542
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539

J. M. J. Williams et al.
FULL PAPERS
Table 2. Allylic alcohols reduced with 1,4-butanediol.
Table 3. Imines reduced with 1,4-butanediol.
Entry
Allylic alcohol substrate 7
Conversion
into alcohol 9 [%][a,b]
1
2
97 (92)
Entry
Imine substrate 10
Conversion
96 (80)[c,d]
into 11 (%)[a,b]
1
2
97 (79)
97 (80)
3
4
100
94 (37)[e,f]
3
4
98 (85)
85 (70)
5
6
95 (75)[d,f]
100 (52)
5
84 (67)
6
7
8
9
96 (80)
95 (84)
97 (87)
96 (84)
7
99 (94)[d,f]
8
97 (91)[f]
95 (62)[e]
91 (80)[e]
10
11
12
99 (84)
99 (86)
98 (85)
9
10
13
95(35)[c]
11
100 (68)
[a] Yields of isolated product are given in parentheses. [b] The alkene
(1 mmol) and 1,4-butanediol (1 mmol) were reacted with [Ru(p-cyme-
ne)Cl2]2 (2.5 mol%), DPEphos (5 mol%), Cs2CO3 (10 mol%) in toluene
(1 mL) in toluene at reflux for 24 h. [c] Separation of product amine
from starting imine by column chromatography was problematic.
12
13
14
100 (71)
76[g]
ACHTUNGTRENNUNG
100 (97)[h]
[a] Yields of isolated product are given in parentheses. [b] The compound
(1 mmol) and 1,4-butanediol (5 mmol) were reacted with [Ru(p-cyme-
ne)Cl2]2 (0.5 mol%), dppf (1 mol%), KOtBu (2 mol%) neat at 1108C for
24 h. [c] The 97% refers to dechlorinated saturated alcohol. [d] Reactions
run for 48 h. [e] Reactions run for 72 h. [f] Reactions were run with [Ru-
hydrolyzed the lactone to the water-soluble carboxylate.
This procedure overcomes the limitation that the lactone
by-product is high boiling (2058C) and is therefore not read-
ily removed by evaporation.
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG(p-cymene)Cl2]2 (2.5 mol%), dppf (5 mol%), KOtBu (10 mol%). [g] The
76% refers to 3-phenyl-1-propanol. The remaining 24% is cinnamyl alco-
hol. [h] The product is 1,3-diphenyl-propan-1-ol.
For the a,b-unsaturated imines (entries 11 and 12), both
the imine and the alkene groups underwent reduction. Keti-
mine (entry 13) was also reduced under the standard condi-
tions.
We also chose to investigate the reduction of alkenes by
ruthenium-catalyzed hydrogen transfer from 1,4-butanediol.
In trial reactions involving the hydrogenation of styrene 12
to diphenylethane 13, we again found that 1,4-butanediol
was a more effective reducing agent than other diols
The reduction of imines by transfer hydrogenation is usu-
ally achieved using formic acid/triethylamine as the reducing
agent, although it has also been reported using alcohols as
the hydrogen donor.[2] We therefore examined the reduction
of a range of imines using 1,4-butanediol as the reducing
(Scheme 4). The combination of [RuACTHNUTRGNEG(NU p-cymene)Cl2]2 with
agent. We found that the use of [Ru
G
DPEphos in the presence of Cs2CO3 was effective for
bination with DPEphos in the presence of Cs2CO3 was ef-
fective for the reduction of a range of imines 10 into amines
11 by transfer hydrogenation from 1,4-butanediol (Table 3).
In spite of the potential for the amine products from
imine reduction to react with the butyrolactone 6 by-prod-
uct, this was not observed under these reaction conditions.
However, separation of the amines from butyrolactone by
column chromatography was not always straightforward.
This problem was easily overcome in the workup by washing
the organic layer with potassium hydroxide solution, which
Scheme 4. Reduction of styrene by transfer hydrogenation.
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Chem. Asian J. 2010, 5, 538 – 542

1,4-Butanediol as a Reducing Agent in Transfer Hydrogenation Reactions
alkene reductions, although in the case of Ru-
ACHTUNGTRENNUNG(PPh3)3(CO)H2, catalytic activity was almost completely re-
moved in the presence of DPEphos.
We then preformed the reduction of a range of alkenes
using [RuACHTUNGTRENNUNG(p-cymene)Cl2]2 with DPEphos and 1,4-butanediol
as the reducing agent (Table 4). Simple alkenes were re-
Table 4. Alkenes reduced with 1,4-butanediol.
Scheme 5. Asymmetric reduction reactions with 1,4-butanediol.
Entry
Alkene substrate
Conversion
into alkane [%]
effect the isomerization were too forcing to allow any appre-
ciable enantiomeric excess to be observed in the reduced
product.
1
2
88 (73)[c]
84
3
4
98 (85)
42
Conclusions
5
6
96 (82)
1,4-Butanediol has been shown to be an effective reducing
agent in ruthenium-catalyzed hydrogen-transfer reactions.
Aldehydes and ketones have been reduced to alcohols,
whereas allylic alcohols undergo an isomerization/reduction
sequence. Imines and alkenes can be reduced to the corre-
sponding amines and alkanes. The main advantage of 1,4-
butanediol as a reducing agent is that the equilibrium prob-
lem found with simpler alcohols is overcome by lactone for-
mation of its oxidation product.
88 (70)[d]
7
8
74 (62)
70 (51)
9
93 (71)[d]
96 (85)[e]
10
[a] Yields of isolated product are given in parentheses. [b] The alkene
(1 mmol) and 1,4-butanediol (1 mmol) were reacted with [Ru(p-cyme-
AHCTUNGTRENNUNG
ne)Cl2]2 (2.5 mol%), DPEphos (5 mol%), Cs2CO3 (10 mol%) in toluene
(1 mL) in toluene at reflux for 24 h. [c] Reactions run for 48 h. [d] Reac-
tions run for 72 h. [e] 96% conversion refers to (E)-1,2-diphenylethene.
Experimental Section
Further details, compound characterization and NMR spectra are avail-
able in the Supporting Information.
duced with good conversions, although a higher catalyst
loading was needed compared with the reduction of allylic
alcohols. The 1,1-disubstituted alkene (entry 4) reacted
more slowly than the other alkenes. Interestingly, it was pos-
sible to reduce the alkyne (entry 10) selectively to the (E)-
alkene, even though there was sufficient 1,4-butanediol pres-
ent for complete reduction.
Typical procedure for reduction of aldehydes and ketones; 1-phenyl-1-
propanol (Table 1, entry 8):[15] To an oven-dried, argon purged carousel
tube charged with RuACHTUNGTRNEG(UN PPh3)3(CO)H2 (22.9 mg, 0.025 mmol), DPEphos
(13.5 mg, 0.05 mmol), and tBuOK (5.6 mg, 0.05 mmol), was added pro-
piophenone (133 mL, 1 mmol), 1,4-butanediol (89 mL, 1 mmol), and tolu-
ene (1 mL). The reaction mixture was heated to reflux for at least 24 h.
The crude reaction mixture was filtered through celite and silica, washed
through with DCM, and concentrated in vacuo. This was then purified by
column chromatography [petroleum ether (b.p. 40–608C)/diethyl ether]
providing 1-phenyl-1-propanol (0.1196 g, 88%). IR (neat): n˜max =3341,
We have also briefly investigated the use of 1,4-butanediol
in asymmetric reactions.[8] By using the Noyori catalyst of
[RuACHTUNGTRENNUNG
(p-cymene)Cl2]2 with (S,S)-TsDPEN,[14] we were able to
1
2964, 2934, 2877, 1592, 1491, 1408 cmÀ1; H NMR (300 MHz, CDCl3): d=
achieve very high enantioselectivity for the reduction of ace-
tophenone, but with modest conversion (Scheme 5). A
higher conversion was achieved in the reduction of 3-chlor-
oacetophenone, using a higher catalyst loading at 408C, but
the enantioselectivity was lower. Nevertheless, it is interest-
ing to note that alternative catalysts are compatible with
1,4-butanediol as a reducing agent, and that hydrogen trans-
fer can be achieved under mild reaction conditions.
We also considered the possibility that an isomerization
of racemic 1-phenyl-prop-2-en-1-ol could proceed via the
achiral ketone with subsequent asymmetric reduction lead-
ing to enantiomerically enriched alcohol. However, using
the Noyori catalyst, the reaction conditions required to
7.28–7.33 (m, 5H, Ph), 4.59 (t, 1H, J=6.5 Hz, CH), 1.76 (m, 2H, CH2),
0.91 ppm (t, 3H, J=7.5 Hz, CH3); 13C NMR (75.4 MHz, CDCl3): d=
143.0, 128.5, 127.3, 119.1, 75.3, 32.0, 9.6 ppm.
Typical procedure for reduction of allylic alcohols; 1-phenyl-1-propanol
(Table 2, entry 1):[15] To an oven-dried, argon-purged carousel tube
charged with [RuACHTUNTRGNEUNG(p-cymene)Cl2]2 (3.1 mg, 0.005 mmol), dppf (3.1 mg,
0.01 mmol), and tBuOK (2.2 mg, 0.02 mmol), was added a-vinylbenzyl al-
cohol (131 mL, 1 mmol) and 1,4-butanediol (0.5 mL, ~5 mmol), and the
mixture was heated to 1108C for at least 24 h. The crude product was pu-
rified by column chromatography (silica gel, Et2O–petroleum ether (b.p.
408C–608C)), providing 1-phenyl-1-propanol (0.1253 g, 92%) as a color-
less liquid. Rf =0.22 (Et2O–petroleum ether (b.p. 408C–608C), 4:1). For
spectroscopy data, see above.
Typical procedure for reduction of imines; N-benzylbenzenamine
(Table 3, entry 1):[16] To an oven-dried, argon-purged carousel tube
Chem. Asian J. 2010, 5, 538 – 542
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J. M. J. Williams et al.
FULL PAPERS
charged with [Ru
(p-cymene)Cl2]2 (15.3 mg, 0.025 mmol) and DPEPHOS
[1] Handbook of Homogeneous Hydrogenation, Vol. 1–3 (Eds: J. G.
de Vries, C. J. Elsevier), Wiley-VCH, Weinheim, 2007.
[2] M. J Palmer, M. Wills, Tetrahedron: Asymmetry 1999, 10, 2045.
[3] S. Gladiali, E. Alberico, Chem. Soc. Rev. 2006, 35, 226.
[4] The equilibrium position can be calculated from the oxidation po-
tential of the ketone. H. Adkins, R. M. Elofson, A. G. Rossow, C. C.
Robinson, J. Am. Chem. Soc. 1949, 71, 3622.
[5] a) C. Delhomme, D. Weuster-Botz, F. E. Kꢂhn, Green Chem. 2009,
11, 13–26; b) I. Bechthold, K. Bretz, S. Kabasci, R. Kopitzky, A.
Springer, Chem. Eng. Technol. 2008, 31, 647–654.
[6] For selected examples, see:a) S. I. Murahashi, T. Naota, K. Ito, Y.
Maeda, H. Taki, J. Org. Chem. 1987, 52, 4319; b) Y. R. Lin, X. C.
Zhu, Y. F. Zhou, J. Organomet. Chem. 1992, 429, 269; c) T. Suzuki,
K. Morita, M. Tsuchida, K. Hiroi, Org. Lett. 2002, 4, 2361.
[7] a) N. Ichikawa, S. Sato, R. Takahashi, T. Sodesawa, K. Inui, J. Mol.
Catal. A 2004, 212, 197; b) J. Zhao, J. F. Hartwig, Organometallics
2005, 24, 2441.
(27.5 mg, 0.05 mmol), was added degassed anhydrous toluene (1 mL),
and the mixture was heated at reflux for 1 h, then allowed to cool to
room temperature. To the resultant red mixture were added Cs2CO3
(32.6 mg, 0.1 mmol), N-benzylidenebenzenamine (190.7 mg, 1 mmol), and
1,4-butanediol (89 mL, 1 mmol) and the resultant red solution was heated
at reflux in toluene for 24 h. On completion, the reaction was allowed to
cool to room temperature, and the solvent was removed in vacuo. The
crude product was dissolved in Et2O (10 mL) and washed with water
(5 mL) and basic aqueous solution of KOH (2ꢁ5 mL, 2m). The organic
phase was dried (MgSO4) and concentrated in vacuo. The crude product
was purified by column chromatography (silica gel, AcOEt-hexane), pro-
viding the title compound (144.7 mg, 79%) as a colorless oil. Rf =0.6
(hexane-AcOEt, 3:1); 1H NMR (300 MHz, CDCl3): d=4.05 (br s, 1H,
NH), 4.45 (s, 2H, CH2), 6.75–7.54 ppm (m, 10H, Ph); 13C{1H} NMR
(75.5 MHz, CDCl3): d=48.8, 113.4, 118.1, 127.8 128.0 129.2, 129.8, 140.0,
148.7 ppm.
[8] H. C. Maytum, B. Tavassoli, J. M. J. Williams, Org. Lett. 2007, 9,
4387–4389.
Typical procedure for reduction of alkenes; 1-methoxy-4-phenethylben-
zene (Table 4, entry 6):[17] To an oven-dried, argon-purged carousel tube
[9] N. J. Wise, J. M. J. Williams, Tetrahedron Lett. 2007, 48, 3639–3641.
[10] a) P. A. Slatford, M. K. Whittlesey, J. M. J. Williams, Tetrahedron
Lett. 2006, 47, 6787–6789; b) S. J. Pridmore, P. A. Slatford, J. M. J.
Williams, Tetrahedron Lett. 2007, 48, 5111–5114; c) S. J. Pridmore,
P. A. Slatford, A. Daniel, M. K. Whittlesey, J. M. J. Williams, Tetra-
hedron Lett. 2007, 48, 5115–5120.
[11] For reviews, see: a) M. H. S. A. Hamid, P. A. Slatford, J. M. J. Wil-
liams, Adv. Synth. Catal. 2007, 349, 1555–1575; b) T. D. Nixon,
M. K. Whittlesey, J. M. J. Williams, Dalton Trans. 2009, 753–762.
[12] A. Wolfson, C. Dlugy, Y. Shotland, D. Tavor, Tetrahedron Lett. 2009,
50, 5951–5953.
[13] V. Cadierno, J. Francos, J. Gimeno, N. Nebra, Chem. Commun. 2007,
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[14] S. Hashiguchi, A. Fujii, J. Takahara, R. Noyori, J. Am. Chem. Soc.
1995, 117, 7562.
[15] S. Brꢃse, S. Dahmen, Chem. Commun. 2002, 26–27.
[16] G. Cami-Kobeci, J. M. J. Williams, Chem. Commun. 2004, 1072.
[17] A. Torii, H. Tanaka, K. Morisaki, Chem. Lett. 1985, 1353.
charged with [RuACHTUNGTRENNUNG(p-cymene)Cl2]2 (15.3 mg, 0.025 mmol) and DPEPHOS
(27.5 mg, 0.05 mmol), was added degassed anhydrous toluene (1 mL),
and the mixture was heated at reflux for 1 h, then allowed to cool to
room temperature. To the resultant red mixture were added Cs2CO3
(32.6 mg, 0.1 mmol), 1-methoxy-4-styrylbenzene (212.4 mg, 1 mmol), and
1,4-butanediol (89 mL, 1 mmol) and the resultant red solution was heated
at reflux toluene for 24 h. On completion, the reaction was allowed to
cool to room temperature, and the solvent was removed in vacuo. The
crude product was dissolved in Et2O (10 mL) and washed with water
(5 mL) and basic aqueous solution of KOH (2ꢁ5 mL, 2m). The organic
phase was dried (MgSO4) and concentrated in vacuo. The crude product
was purified by column chromatography (silica gel, AcOEt-hexane), pro-
viding the title compound (148.6 mg, 70%) as a colorless solid. Rf =0.5
(hexanes-AcOEt, 100:1); 1H NMR (300 MHz, CDCl3): d=2.77 (s, 4H,
CH2), 3.67 (s, 3H, OCH3), 6.70–7.21 ppm (m, 9H, Ph); 13C{1H} NMR
(75.5 MHz, CDCl3): d=37.5, 38.7, 55.7, 114.2, 128.9, 126.3, 128.7, 129.8,
134.3, 142.3, 158.3 ppm.
Received: October 6, 2009
Published online: January 28, 2010
Acknowledgements
We thank GlaxoSmithKline and EPSRC for the award of an industrial
CASE studentship to HCM.
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Chem. Asian J. 2010, 5, 538 – 542