DOI: 10.1002/cctc.201500886
Communications
Alternative Hydrogen Source for Asymmetric Transfer
Hydrogenation in the Reduction of Ketones
[a]
[b]
[a]
Russell J. Wakeham,* James A. Morris, and Jonathan M. J. Williams
cis-1,4-Butenediol is shown to be a highly active hydrogen
source for asymmetric transfer hydrogenation in the reduction
of ketones. With the use of a ruthenium catalyst, cis-1,4-bu-
tenediol is isomerised and subsequently oxidised to a lactone
as an irreversible step, which provides the driving force for the
asymmetric reduction of ketones.
using (S,S)-tethered-TsDPEN RuCl (Wills Catalyst) as a catalyst.
cis-1,4-Butenediol is synthesised on an industrial scale from 2-
butyne-1,4-diol and is important in the production of endosul-
[
8]
[9]
fan and Vitamins A and B and is an additive in resin manu-
[
10]
facturing.
2-Butyne-1,4-diol is synthesised from the Reppe
carbonylation of acetylene using formaldehyde as the carbonyl
[
11]
[12]
source, therefore, it is produced cheaply. Lindlar’s catalyst
[
9,13]
[14]
as well as many supported Pd
and Ni catalysts are able
Catalytic transfer hydrogenation (TH) has been well reported in
the literature, and the most prevalent sources of hydrogen are
derived from either isopropanol or an azeotropic mixture of
to hydrogenate butynediol to butenediol selectively. Therefore,
this is considered a suitably cheap available hydrogen source
for these investigations.
[1]
formic acid with triethylamine (5:2). Catalyst systems that use
Previously, our group has shown that 1,4-butanediol can be
[2]
[3]
[4] [5]
[6]
[15]
a variety of metal centres, such as Al, Ru, Rh, Ir and Fe,
used as a hydrogen source for TH reactions. We wished to
have been reported with improvements made to these
systems.
extend this methodology to the more commercially desirable
ATH protocol. We proposed to investigate the difference be-
tween cis-1,4-butenediol and 1,4-butanediol on the basis that
the slow oxidation step of 1,4-butanediol to form 4-hydroxybu-
tanal could be circumvented by using cis-1,4-butenediol and
selecting a catalyst that was efficient for the isomerisation of
allylic alcohols (Scheme 1). cis-1,4-Butenediol was, therefore,
chosen to be investigated given that the isomerisation of cis-
1,4-butenediol to 4-hydroxybutanal is catalysed readily by Ru
Ru-catalysed asymmetric transfer hydrogenation (ATH) is
a well-established protocol. Noyori and Hashiguchi used chiral
II
Ru complexes with mono-tosylated diamines to catalyse the
[
3b]
ATH of ketones.
The most widely used derivative of the
chiral catalyst is formed in situ from the reaction of the di-
chlororuthenium(II) p-cymene dimer and (1S,2S)-(+)-N-(4-tolu-
enesulfonyl)-1,2-diphenylethylenediamine (TsDPEN) in the pres-
ence of a base, usually potassium hydroxide.
[
16]
TH catalysts.
Modifications to the standard Noyori system have been re-
[
3c]
ported, in particular Wills et al. reported the use of tethered
II
Ru catalysts that have excellent stability and provide high
[7]
levels of enantioselectivity. Despite the advances of these cat-
alyst systems, there are still issues with the use of either of the
two most common hydrogen sources. For every molecule of
isopropanol that is oxidised, acetone is produced, which is
often reduced more easily by the catalyst than the substrate
ketone. A large excess of isopropanol is, therefore, required to
drive the reaction to near completion. The ubiquitous formic
acid/triethylamine (5:2) azeotropic mixture, although it is effi-
cient as a hydrogen source, produces a stoichiometric amount
of CO2.
Scheme 1. Possible pathways for hydrogen abstraction from 1,4-butanediol
and cis-1,4-butenediol in the presence of [Ru(p-cymene)Cl
2 2
] .
Initial optimisation focused on the use of [Ru(p-cymene)Cl2]2
in conjunction with KOH and (S,S)-TsDPEN. A solvent screen
showed that toluene and THF gave the best conversions and
maintained high enantioselectivities, so to ensure the ready
solubility of the reagents THF was chosen. We used 10 mol%
KOH and varied the concentration of 1,4-butanediol versus cis-
Herein we describe a highly active prospective hydrogen
source, cis-1,4-butenediol, which to the best of our knowledge
has not been investigated in ATH reactions previously. The diol
has been optimised for the asymmetric reduction of ketones
1
,4-butenediol and identified that 0.5 equivalents of 1,4-bu-
[
a] Dr. R. J. Wakeham, Prof. J. M. J. Williams
Department of Chemistry, University of Bath
Claverton Down, BA2 7AY (UK)
tanediol provided excellent enantioselectivity but poor conver-
sion (Table 1, entry 4). However, the turnover for this pathway
appears to become inhibited, which presumably confirms the
pathway depicted in Scheme 1. Hence an increase of the
amount of 1,4-butanediol in the reaction mixture results in
small increases in conversion with the concurrent suppression
of enantioselectivity (Table 1, entries 5–6). This reduction in se-
E-mail: rwakeham@chem.ubc.ca
[
b] J. A. Morris
Syngenta, Chemical Research
Jealott’s Hill, Bracknell, RG42 6EY (UK)
ChemCatChem 2015, 7, 4039 – 4041
4039
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim