One-pot Chemoenzymatic Deracemisation of Secondary Alcohols Employing Variants of Galactose Oxidase and Transfer Hydrogenation

Article abstract of DOI:10.1002/cctc.202001191

Enantiomerically enriched chiral secondary alcohols serve as valuable building blocks for drug intermediates and fine chemicals. In this study the deracemisation of secondary alcohols to generate enantiomeric pure chiral alcohols has been achieved by combining enantio-selective enzymatic oxidation of a secondary alcohol, by a variant of GOase (GOase M_3-5), with either non-selective ketone reduction via transfer hydrogenation (TH) or enantio-selective asymmetric transfer hydrogenation (ATH). Both the enzymatic oxidation system and the transition-metal mediated reduction system were optimised to ensure compatibility with each other resulting in a homogeneous reaction system. 1-(4-nitrophenyl)ethanol was generated with 99 % conversion and 98 % ee by the deracemisation method, and it has been extended to a series of other secondary alcohols with comparable results.

Full text of DOI:10.1002/cctc.202001191

The European Society Journal for Catalysis
Supported by
Accepted Article
Title: One-pot Chemoenzymatic Deracemisation of Secondary
Alcohols Employing Variants of Galactose Oxidase and Transfer
Hydrogenation
Authors: Nicholas John Turner, Bo Yuan, Damien P. Debecker,
Xiaofeng Wu, Jianliang Xiao, and Qiang Fei
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: ChemCatChem 10.1002/cctc.202001191
Link to VoR: https://doi.org/10.1002/cctc.202001191
0
1/2020

ChemCatChem
10.1002/cctc.202001191
COMMUNICATION
One-pot Chemoenzymatic Deracemisation of Secondary Alcohols
Employing Variants of Galactose Oxidase and Transfer
Hydrogenation
Bo Yuan[a,d], Damien P. Debecker , Xiaofeng Wu , Jianliang Xiao , Qiang Fei* , Nicholas J.
[b]
[c]
[c]
[a]
Turner*[d]
[
a]
Dr. B. Yuan, Prof. Q. Fei
School of Chemical Engineering and Technology
Xi'an Jiaotong University
No. 28, Xianning West Road, Xi'an 710049, P. R. China
E-mail: bo.yuan@xjtu.edu.cn, feiqiang@xjtu.edu.cn
Prof. D. P. Debecker
Institute of Condensed Matter and Nanosciences (IMCN)
Université catholique de Louvain (UCLouvain)
Place Louis Pasteur, 1, box L4.01.09, 1348 Louvain-La-Neuve, Belgium
Dr. X. Wu, Prof. J. Xiao
[
b]
c]
[
Department of Chemistry
University of Liverpool
L69 7ZD, Liverpool
United Kingdom
[d]
Prof. N. J. Turner
Department of Chemistry
University of Manchester
Manchester Institute of Biotechnology, 131 Princess Street, M1 7DN
United Kingdom
E-mail: nicholas.turner@manchester.ac.uk
*
Corresponding authors: Prof. Qiang Fei, feiqiang@xjtu.edu.cn, and Prof. Nicholas J. Turner, nicholas.turner@manchester.ac.uk
Supporting information for this article is given via a link at the end of the document.
Abstract: Enantiomerically enriched chiral secondary alcohols serve
as valuable building blocks for drug intermediates and fine chemicals.
In this study the deracemisation of secondary alcohols to generate
enantiomeric pure chiral alcohols has been achieved by combining
enantio-selective enzymatic oxidation of a secondary alcohol, by a
variant of GOase (GOase M3-5), with either non-selective ketone
reduction via transfer hydrogenation (TH) or enantio-selective
asymmetric transfer hydrogenation (ATH). Both the enzymatic
oxidation system and the transition-metal mediated reduction system
were optimised to ensure compatibility with each other resulting in a
homogeneous reaction system. 1-(4-nitrophenyl)ethanol was
generated with 99% conversion and 98% ee by the deracemisation
method, and it has been extended to a series of other secondary
alcohols with comparable results.
investigated the deracemisation of secondary alcohols by
combining GOase mediated oxidation with transition metal
catalysed reduction. Previous reports have shown that it is
possible to obtain enantio-pure secondary alcohols in high
conversions by either employing one[13] or two[14-16] microbial
[17]
systems, an organocatalytic system and a microbial system , a
transition metal catalyst with an enzyme by deracemisation[ or
18]
dynamic kinetic resolution (DKR) [19-21], and by stereoinversion[22]
.
One example for the deracemisation of secondary alcohols
employing a combination of enzymes and transition metal
catalysts was reported by Mutti et al[18]. They employed an iridium
metal catalyst, for the non-selective oxidation, with an enzyme,
ADH-A, for the asymmetric reduction, to achieve deracemisation
of secondary alcohols, affording a 99.9% yield and a moderate
40% ee.
During the process of screening for a suitable reducing agent
Deracemisation reactions, in which a racemate is converted into
either single enantiomer, are attractive processes since they
overcome the 50% conversion limit of kinetic resolution (KR) and
therefore represent an important approach for the synthesis of
enantio-pure compounds[1-4]. Previous work has shown that a
variant of the enzyme galactose oxidase (GOase M3-5) is capable
of oxidising a wide range of chiral secondary alcohols to the
to work in conjunction with GOase, we observed that classical
reducing agents such as sodium borohydride and borane-
ammonia complex rendered complete loss of activity of the
enzyme. This may be because the active copper centre present
in GOase is reduced by the reducing agents. Consequently, we
turned our focus to TH and ATH using transition metal catalysts
(
Scheme 1) that we have previously reported. These TH catalysts
[
5]
corresponding ketones with high enantioselectivity . Various
variants of GOase have found numerous applications in areas
are highly efficient in mediating reduction of ketones to secondary
alcohols[23-25]. Moreover, these catalysts are soluble in water,
active at neutral pH, and stable in air, suggesting that they could
be ideal candidates for combining with enzymes for the
deracemisation of secondary alcohols.
[
6-7]
including enantio-selective oxidation of atropisomers
and
[
8]
[9]
amino alcohols , glycoprotein labeling , converting alcohols to
nitriles[ , or to carboxylic acids by a “through oxidation”
process[11]. The process aspects for GOase applications have
also been thoroughly reviewed[12]. In this paper we have
10]
1
This article is protected by copyright. All rights reserved.

ChemCatChem
10.1002/cctc.202001191
COMMUNICATION
the presence of a transition metal catalyst has a significant effect
on the biocatalytic oxidation reaction. At 14.6 µM enzyme
concentration, only a minimum of 125 substrate/catalyst ratio
(
S/C) can be used without loss of ee (Table 1, Entry 1-4). However,
this metal catalyst concentration is too low for high conversions in
the TH reaction. As a result, the concentration of the enzyme was
increased to 29.2 µM to allow a higher concentration of metal
catalyst. Indeed, with a S/C of 25, only 4% loss of ee was
observed (Table 1, Entry 8). Therefore, S/C ratios close to 25 –
M-TsDPEN (M = Rh, Ir) M-TsCYDN (M = Rh, Ir)
Scheme 1. Examples of transition metal catalysts used in ATH
30 and 29.2 µM GOase concentration were employed in
Herein we demonstrate the deracemisation of secondary
alcohols by combination of GOase M3-5 catalysed enantio-
selective oxidation system with a non-selective reduction by TH
subsequent deracemisation reactions.
We also explored the effect of concentration of sodium
formate on the activity of GOase (Supporting information, Table
S2). It turned out that the addition of HCOONa had a negative
effect on the biocatalytic oxidation reaction and the higher
concentration of sodium formate, the more ee decreased for the
production of chiral alcohols. For example, by increasing the
concentration of HCOONa from ca. 0.5 M to 1.76 M, a significant
(
Scheme 2), affording both high ee and conversions (up to 99%).
We selected the substrates 3'-fluoro-acetophenone and 4'-nitro-
acetophenone as model substrates based on the low enantio-
selectivity observed with ATH, and the high activity shown by
GOase for oxidation of the corresponding secondary alcohols.
27% loss of ee was observed. Therefore, in the following
deracemisation reactions, the concentrations of HCOONa were
restricted to near ca. 0.5 mM.
Next, we studied the impact of the components of the
enzymatic oxidation system on the TH system. The major
components that may potentially affect the performance of the
reduction system are oxygen bubbling (by means of bubbling
oxygen through the reaction mixture), which is used to provide the
oxidant for the bio-oxidation by the requisite enzymes, namely
catalase, HRP and GOase. The presence of the three enzymes
was found to have little effect on the TH system. However, oxygen
has been reported to serve as a competing hydrogen acceptor via
Scheme 2. Deracemisation of secondary alcohols generated from TH of
ketones.
direct reaction of the metal hydride intermediate with molecular
To investigate the compatibility of the oxidation system and
the reduction system, the effect of each component of the system
on the other components was initially examined. TH of ketones
requires both the transition metal catalyst and the hydrogen donor
sodium formate (HCOONa), whereas the biocatalytic oxidation of
alcohols requires the enzyme GOase, oxygen, catalase and
horseradish peroxidase (HRP). Firstly a series of biocatalytic
oxidation reactions were performed in the presence of various
concentrations of the metal catalyst (rac)-Ir-TsCYDN (Table 1).
oxygen. [
24, 26]
By performing the ketone reduction using transition
metal catalysts with and without oxygen bubbling, we confirmed
that conversions were reduced by up to 30% when oxygen was
present (Supporting Information, Table S1). Elimination of oxygen
bubbling only resulted in a 5% loss of ee in the bio-oxidations
reactions and therefore, no oxygen bubbling was employed for
the optimised reaction conditions in the following studies.
Since the GOase reaction appeared to be more sensitive to
the effect of the TH components, rather than vice-versa, further
optimisation of the TH system was conducted.
Initially, various metal - ligand combinations were inspected
for ketone reduction (Supporting information, Table S3). Both
(rac)-Rh-TsCYDN and (rac)-Ir-TsCYDN were selected as the
optimal catalysts for applications in further deracemisation
rections .
Table 1. Optimisation of biocatalytic oxidation of secondary alcohols in the
presence of (rac)-Ir-TsCYDN.
(
rac)-Ir-
S/C
(with Ir
catalyst)
Enzyme
concentration
[µM]
Entry
Time [h]
TsCYDN
ee [%]
[mM]
1
2
3
4
18
18
18
18
0.2
250
125
100
100
88
14.6
14.6
14.6
14.6
0.4
0.8
1.2
Table 2. Optimisation of metal catalysts concentrations.
62.5
41.7
Entry
Time [h]
Metal catalysts
(rac)-Rh-TsCYDN
(rac)-Rh-TsCYDN
(rac)-Rh-TsCYDN
(rac)-Rh-TsCYDN
(rac)-Rh-TsCYDN
(rac)-Ir-TsCYDN
(rac)-Ir-TsCYDN
(rac)-Ir-TsCYDN
(rac)-Ir-TsCYDN
(rac)-Ir-TsCYDN
(rac)-Ir-TsCYDN
(rac)-Ir-TsCYDN
S/C
100
83
71
31
31
100
83
71
63
Alcohol [%]
50
1
2
3
4
5
6
7
8
3
3
3
1
3
3
3
3
3
3
1
3
77
81
84
79
99
87
89
93
99
99
97
99
5
6
7
8
24
24
24
24
0.8
1
1.6
2
62.5
50
31.3
25
100
100
100
96
29.2
29.2
29.2
29.2
Reaction conditions: 50 mM 3'-fluorophenylethanol, 0.2-2 mM (rac)-Ir-TsCYDN,
4.6 – 29.2 μM GOase, 22 μM HRP, 0.4 μM catalase, 37˚C, 900 rpm, total
1
volume: 0.5 mL in water.
10
1
1
50
31
31
The catalyst (rac)-Ir-TsCYDN was prepared by combining the
12
metal complex [(Cp*IrCl
2
)
2
] and the ligand racemic TsCYDN in
13
distilled water as previously reported[23]. This solution was then
used directly in the TH reaction. From Table 1, it can be seen that
2
This article is protected by copyright. All rights reserved.

ChemCatChem
10.1002/cctc.202001191
COMMUNICATION
To demonstrate the generality of this method, a range of
substrates were deracemised using the optimised reaction
conditions.
Reaction conditions: 25 mM 4'-nitro-acetophenone, 37˚C, 900 rpm, 0.2 - 0.8 mM
(rac)-Ir-TsCYDN/(rac)-Rh-TsCYDN, 588 mM HCOONa (24 equiv.), total
volume: 0.5 mL in water.
As shown in Table 4, the deracemisation system was
successfully applied for the production of a range of enantio-pure
chiral secondary alcohols. In general, meta-substituted aryl
ketones are typically difficult substrates for asymmetric reduction
by ATH with transition metal catalysts, affording maximum
selectivities of approximately 90% ee typically. [26] A notable
improvement in ee was observed with the meta-substituted
substrates (Table 4, entry 2, 6 and 7) by deracemisation
compared to ATH, representing the advantage of the current
combined system. In addition, the electron deficient substrate
pentafluoro-acetophenone (Table 4, entry 8) gave a very good ee
and conversion, demonstrating that the deracemisation process
is highly tolerant of various substrates with different substituents.
To further identify optimum S/C ratios for the transition metal
catalysts to be employed in deracemisations, a range of reactions
were performed with various concentrations of the catalysts at
S/C ratios ranging from 31-100. The purpose of these studies was
to identify the maximum concentration of metal catalysts that
could be used to sufficiently reduce the ketone without impairing
the activity of the enzyme.
It was found that with S/C ratios ranging from 71-100, neither
(
rac)-Rh-TsCYDN nor (rac)-Ir-TsCYDN was able to catalyse the
complete reduction of the ketone substrate (Table 2). However,
9% conversion to the alcohol was obtained when (rac)-Ir-
TsCYDN was used with S/C ratios ranging from 31-63, or with
rac)-Rh-TsCYDN with a S/C ratio of 31. Entries 4 and 12 show
9
(
that at a S/C ratio of 31, the reaction using (rac)-Rh-TsCYDN
showed lower conversions at 1 h compared to (rac)-Ir-TsCYDN,
with 18% less alcohol produced, although the conversions were
comparable at 3 h. With the objective of reducing the overall
reaction time of the deracemisation reactions, (rac)-Ir-TsCYDN
was identified as the best catalyst to perform the TH reaction in
conjunction with the enzymatic oxidations by GOase (Table 3).
Table 4. Deracemisation of a range of secondary alcohols.
Time
[h]
ee
[%]
Alcohol
[%]
Entry
Substrates
Products
1
48
48
98
99
99
70
2
Table 3. Deracemisation of 1-(4-nitrophenyl)ethanol generated by TH of the
ketone.
3
4
48
48
99
99
81
88
Time [h]
.5
ee [%]
Alcohol [%]
1
1*
99
5
24
99
25
Addition of GOase
3
6
94
96
96
98
78
81
92
99
6
7
8
48
48
48
91
99
89
99
90
92
24
48
Reaction conditions: 1). Reduction. 25 mM 4'-nitro-acetophenone, 37˚C, 900
rpm, 0.8 mM (rac)-Ir-TsCYDN (S/C=31), 588 mM HCOONa (24 equiv.), total
volume: 0.5 mL in water. 2). Oxidation. 29.2 μM GOase M3-5, 22 μM HRP, 0.4
μM catalase.
*
1% ee may be due to error or impurities.
The reaction was initiated by firstly performing the non-
selective reduction step on the ketone substrate 4'-nitro-
acetophenone with the conversion to the racemic alcohol
reaching 99% after 1.5 h. Subsequently, GOase was added, and
the ee increased to 94% during next 1.5 h as a result of enantio-
selective oxidation by GOase. After a longer period of time both
ee and the alcohol composition progressively increased to 98%
and 99% respectively (Table 3), leaving only (S)-enantiomer of
the alcohol in the reaction mixture. At this point there was trace
amount of ketone or (R)-enantiomer of the alcohol remaining as
shown from the HPLC traces of the final reaction mixture (Figure
S9).
Reaction conditions: 1). Reduction. 25 mM substrates, 37 °C, 900 rpm, 0.8 mM
rac)-Ir-TsCYDN (S/C = 31), 588 mM HCOONa, total volume: 0.5 mL. 2).
Oxidation. 29.2 µM GOase M3-5, 22 µM HRP, 0.4 µM catalase.
(
In addition to the deracemisation reactions employing the
(
rac)-Ir-TsCYDN catalyst, boosting the enantio-selectivity with
ATH by (S)-selective catalysts was also examined. The ATH by
the (S)-selective Rh-TsDPEN has been previously applied in the
reduction of a wide range of ketone substrates with generally high
selectivity (ee > 94% for over 20 examples); but in some cases a
lower ee was observed. For example, an ee of 88% was obtained
for the reduction of 4'-nitro-acetophenone by the (S)-selective Rh-
TsDPEN as reported by Wu et al[ . However, deracemisation
26]
3
This article is protected by copyright. All rights reserved.

ChemCatChem
10.1002/cctc.202001191
COMMUNICATION
reactions employing the (S)-selective Rh-TsDPEN metal catalyst
combined with GOase achieved excellent ee as well as
conversions for the chiral alcohol products (Scheme 3).
employing ATH alone. The deracemisation system was also
expanded to
a range of secondary alcohols with varied
functionalities. ee and conversions to some of the
challenging/problematic substrates under sole TH/ATH conditions
were also improved.
Acknowledgements
This work was funded by the National Natural Science
Foundation of China (21706205), the China Postdoctoral Science
Foundation (2018M633518), and the Natural Science Foundation
of Shaanxi Province (2018JQ2062). D.P. Debecker thanks the
Francqui foundation for his Francqui Research Professor chair.
We also thank the Instrument Analysis Center of Xi'an Jiaotong
University for help with characterizations.
Scheme 3. Deracemisation employing (S)-selective Rh-TsDPEN.
Since in this case the metal catalyst also contributes to the
final ee of the product, the reaction conditions were less restrictive
lower concentrations of enzyme and transition metal catalysts
can be used) compared to the reactions employing the racemic
transition metal catalysts.
(
Keywords: biocatalysis • chiral secondary alcohols • galactose
oxidase • deracemisation • transfer hydrogenation
1
00
100
9
8
7
6
5
4
0
0
0
0
0
0
9
9
9
9
9
8
8
8
6
4
2
0
8
6
ee
Acetophenone
Alcohol
[1].
2].
N.J. Turner, Curr. Opin. Chem. Biol. 2010, 14 (2), 115-121.
(
M. Rachwalski, N. Vermue, F. P. J. T. Rutjes, Chem. Soc. Rev. 2013, 42
(
24), 9268-9282.
A. Diaz-Rodriguez, I. Lavandera, V. Gotor, Curr. Green Chem. 2015, 2
2), 192-211.
[3].
(
30
[
4].
N. J. Turner, Curr. Opin. Chem. Biol. 2004, 8 (2), 114-119.
2
1
0
0
0
[5].
F. Escalettes, N. J. Turner, Chembiochem 2008, 9 (6), 857-860.
B. Yuan, A. Page, C. P. Worrall, F. Escalettes, S. C. Willies, J. J. W.
McDouall, N. J. Turner, J. Clayden, Angew. Chem., Int. Ed. 2010, 49 (39),
[
[
[
6].
7].
8].
0
10
20
30
Time [h]
7010-7013.
S. Staniland, B. Yuan, N. Gimenez-Agullo, T. Marcelli, S. C. Willies, D.
Figure 1. Deracemisation of 1-(4-nitrophenyl)ethanol generated by (S)-
selective Rh-TsDPEN (Time = 0 h marked as the start time of the second
oxidation step). Reaction conditions: 1). Reduction. 50 mM 4'-nitro-
acetophenone, 30 °C, 250 rpm, 0.2 mM (S)-selective Rh-TsDPEN (S/C =
M. Grainger, N. J. Turner, J. Clayden, Chem. - Eur. J. 2014, 20 (41),
13084-13088.
S. Herter, S. M. Mckenna, A. R. Frazer, S. Leimkühler, A. J. Carnell, N.
J. Turner, Chemcatchem 2015, 7 (15), 2313-2317.
2
50), 147 mM HCOONa, total volume: 0.5 mL. 2). Oxidation. 14.6 µM GOase
M3-5, 22 µM HRP, 0.4 µM catalase.
[9].
J. B. Rannes, A. Ioannou, S. C. Willies, G. Grogan, C. Behrens, S. L.
Flitsch, N. J. Turner, J. Am. Chem. Soc. 2011, 133 (22), 8436-8439.
[
10]. J. Vilim, T. Knaus, F. G. Mutti, Angew. Chem., Int. Ed. 2018, 57 (43),
4240-14244.
1
In Figure 1, time = 0 h represents the start of the second
[
[
11]. W. R. Birmingham, N. J. Turner, ACS Catal. 2018, 8 (5), 4025-4032.
12]. A. T. Pedersen, W. R. Birmingham, G. Rehn, S. J. Charnock, N. J. Turner,
J. M. Woodley, Org. Process Res. Dev. 2015, 19 (11), 1580-1589.
step of the reaction (oxidation) after the reduction had completed,
leaving 87% ee of the alcohol and <5% ketone in the reaction
mixture. After addition of the components from the oxidations
system, ee and conversions reached 99% and 96% after 3 h,
respectively. These results were achieved with only 14.6 µM
GOase at S/C = 250, which means that the concentrations of both
enzymes and metal catalysts were lower than the
deracemisations using the racemic metal catalyst (rac)-Ir-
TsCYDN. In the end, the combination of GOase with (S)-selective
Rh-TsDPEN leads to a 12% improvement in ee compared with
performing only the reduction of the ketone by (S)-selective Rh-
TsDPEN, which demonstrates the effectiveness of the
deracemisation method.
[13]. I. Karume, M. Takahashi, S. M. Hamdan, M. M. Musa, Chemcatchem
2016, 8 (8), 1599-1599.
[14]. C. V. Voss, C. C. Gruber, K. Wolfgang, Angew. Chem. 2010, 47 (4), 741-
7
45.
15]. F. D. Nasario, P. J. S. Moran, J. A. R. J. Rodrigues, Braz. Chem. Soc.
019, 30 (4), 772-779.
[
[
2
16]. M. Schober, M. Toesch, T. Knaus, G. A. Strohmeier, B. van Loo, M.
Fuchs, F. Hollfelder, P. Macheroux, K. Faber, Angew. Chem., Int. Ed.
2013, 52 (11), 3277-3279.
[17]. E. Liardo, N. Rios-Lombardia, F. Moris, J. Gonzalez-Sabin, F. Rebolledo,
Eur. J. Org. Chem. 2018, (23), 3031-3035.
[18]. F. G. Mutti, A. Orthaber, J. H. Schrittwieser, J. G. de Vries, R. Pietschnig,
W. Kroutil, Chem. Comm. 2010, 46 (42), 8046-8048.
In summary, we have successfully combined an enantio-
selective enzyme GOase with a racemic metal catalyst (rac)-Ir-
TsCYDN to achieve the deracemisation of secondary alcohols to
highly enantiomerically enriched chiral alcohol products. By
optimising each of the biocatalytic oxidation and chemocatalytic
reduction steps, deracemisation was achieved by employing the
enzyme GOase ((R)-selective) and a racemic transition metal
catalyst. Outstanding ee and conversions were obtained. When
the (S)-selective Rh-TsDPEN was applied in the deracemisation
process, both ee and conversions were improved compared to
[
[
[
19]. B. Martín-Matute, M. Edin, K. Bogár, F. B. Kaynak, J. –E. Bäckvall, J. Am.
Chem. Soc. 2005, 127 (24), 8817-8825.
20]. B. A. Persson, A. L. E. Larsson, M. L. Ray, J. –E. Bäckvall, J. Am. Chem.
Soc. 1999, 121 (8), 1645-1650.
21]. R. M. Haak, F. Berthiol, T. Jerphagnon, A. J. A. Gayet, C. Tarabiono, C.
P. Postema, V. Ritleng, M. Pfeffer, D. B. Janssen, A. J. Minnaard, B. L.
Feringa, J. G. de Vries, J. Am. Chem. Soc. 2008, 130 (41), 13508-13509.
[22]. C. V. Voss, C. C. Gruber, K. Faber, T. Knaus, P. Macheroux, W. Kroutil,
J. Am. Chem. Soc. 2008, 130 (42), 13969-13972.
4
This article is protected by copyright. All rights reserved.

ChemCatChem
10.1002/cctc.202001191
COMMUNICATION
[
23]. X. Wu, J. Liu, X. Li, A. Zanotti-Gerosa, F. Hancock, D. Vinci, J. Ruan,;J.
Xiao, Angew. Chem., Int. Ed. 2006, 45 (40), 6718-6722.
[
24]. X. Wu, D. Vinci, T. Ikariya, J. Xiao, Chem. Comm. 2005, 37 (35), 4447-
4449.
[
[
25]. X. Wu, C. Wang, J. Xiao, Chemical Record 2016, 16 (6), 2768-2782.
26]. X. Wu, X. Li, A. Zanotti-Gerosa, A. Pettman, J. Liu, A. J. Mills, J. Xiao,
Chem. – Eur. J. 2008, 14 (7), 2209-2222.
5
This article is protected by copyright. All rights reserved.

ChemCatChem
10.1002/cctc.202001191
COMMUNICATION
Table of Contents
Chiral secondary alcohols were synthesized in up to 99% ee and 98% conversions by deracemisation methods. These methods can
be achieved by employing an asymmetric oxidation of the alcohol substrates with a non-asymmetric or asymmetric reduction of the
ketones in one-pot. The galactose oxidase M3-5 variant was utilised as the biocatalyst for the oxidation of the alcohols, and Transfer
hydrogenation (TH) or asymmetric transfer hydrogenation (ATH) were employed for the reduction of the corresponding ketones.
6
This article is protected by copyright. All rights reserved.