RhIII-Catalyzed Asymmetric Transfer Hydrogenation of Α-Methoxy Β-Ketoesters through DKR in Water: Toward a Greener Procedure

Article abstract of DOI:10.1002/cssc.201900358

The asymmetric reduction of α-methoxy β-ketoesters through transfer hydrogenation with a new rhodium(III) complex was developed. The reaction was efficient in 2-MeTHF with formic acid/triethylamine or in water with sodium formate. The corresponding syn α-

Full text of DOI:10.1002/cssc.201900358

Accepted Article
Title: Novel Rh(III)-Catalyzed Asymmetric Transfer Hydrogenation of
α-Methoxy β-Ketoesters via DKR in Water: Toward a Greener
Procedure
Authors: Virginie Vidal, Bin He, Long-Sheng Zheng, and Phannarath
Phansavath
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: ChemSusChem 10.1002/cssc.201900358
Link to VoR: http://dx.doi.org/10.1002/cssc.201900358
A Journal of
www.chemsuschem.org

10.1002/cssc.201900358
ChemSusChem
COMMUNICATION
Novel Rh(III)-Catalyzed Asymmetric Transfer Hydrogenation of α-
Methoxy β-Ketoesters via DKR in Water: Toward a Greener
Procedure
Bin He,[a] Long-Sheng Zheng,[a] Phannarath Phansavath*[a] and Virginie Ratovelomanana-Vidal*[a]
The asymmetric reduction of α-methoxy β-ketoesters through
transfer hydrogenation using a new rhodium(III) complex is reported.
The reaction was efficient in 2-MeTHF with formic acid/triethylamine
or in water with sodium formate. The corresponding syn α-methoxy
β-hydroxyesters were obtained with high diastereoselectivities and
excellent levels of enantioselectivity via a dynamic kinetic resolution
process.
In these instances, the reaction was performed on bicyclic β-
ketoesters with a Rh catalyst formed from a chiral double-chain
surfactant-type ligand giving high enantioselectivities and
diastereoselectivities but moderate yield for the 6-membered β-
hydroxyester. Herein we report an environmentally sustainable
procedure for the ATH/DKR of α-alkoxy β-ketoesters in water
involving a new rhodium complex (Figure 1). In line with the 12
principles of green chemistry,[7] one key point of our ATH/DKR
process was to use an easy-to-handle and air-stable complex
that would operate under environmentally sound conditions. As
part of our ongoing studies aimed at developing efficient
catalysts for the asymmetric reduction of unsaturated
compounds, we recently developed a series of tethered rhodium
complexes (R,R)-A–(R,R)-D,[8] analogous to Wills' complex,[9]
that we chose to evaluate in this study and additionally, we
Although numerous methods are available for the
enantioselective preparation of 1,2-diol derivatives,[1] most of
them do not allow differentiation of the two hydroxyl functions
and only few examples of the preparation of monodifferentiated
diols have been described.[2] A straightforward and atom-
economical access to such compounds involves the asymmetric
reduction through dynamic kinetic resolution (DKR)[3] of racemic
α-alkoxy β-ketoester derivatives. In this context, we have
prepared
a
new N-pentafluorophenylsulfonyl-DPEN-based
tethered Rh(III) complex (R,R)-E[10] (see the Supporting
reported in
a
previous work the asymmetric transfer
Information) (Figures 2 and 3).
hydrogenation (ATH)[4] of these compounds through DKR to
access the corresponding enantiomerically enriched syn α-
alkoxy β-hydroxyesters directly[5] by using ruthenium complexes
in dichloromethane and a 5:2 mixture of formic acid/triethylamine
as the hydrogen source. In search of a greener approach, we
decided to investigate this reaction in more ecofriendly solvents
and water appeared as the solvent of choice for this
transformation. As far as rhodium-catalyzed asymmetric transfer
hydrogenation through DKR in water is concerned, to the best of
our knowledge, only two examples were previously disclosed[6]
(Figure 1).
Rh
N
Rh
N
Rh
N
Cl
Cl
Cl
MeO
Me
F
TsN
TsN
TsN
H
H
H
Ph
Ph
Ph
Ph
Ph
Ph
(R,R)-C
(R,R)-A
(R,R)-B
Rh
Rh
Cl
H
Cl
F3C
O
S
TsN
N
N
N
C6F5
H
Ph
O
Ph
(R,R)-E
Ph
Ph
(R,R)-D
Previous work:[6]
O
OH
n
O
O
Figure 2. Rhodium complexes used in this study.
[RhCl2Cp*]2, L
HCO2Na, H2O, 40 °C
OEt
OEt
n
n = 1,2
n = 1, 95%, 99:1 dr, 98% ee
n = 2, 51%, 97:3 dr, 99% ee
O
O
L:
N
N
2I
N
N
H
H
O
H2N
NH S
O
This work:
OH
O
O
O
(R,R)-E, HCO2Na
R
OMe
R
OMe
CTAB, H2O, 40 °C
OMe
OMe
Figure 1. Rhodium-catalyzed ATH/DKR in water.
[a]
B. He, L.-S. Zheng, Dr P. Phansavath, Dr V. Ratovelomanana-Vidal
PSL Research University, Chimie ParisTech, CNRS, i-CLeHS
(Institute of Chemistry for Life & Health Sciences), CSB2D team
75005 Paris, France
Figure 3. X-Ray crystallographic structure of (R,R)-E (hydrogen atoms are
omitted for clarity).
phannarath.phansavath@chimieparistech.psl.eu;
virginie.vidal@chimieparistech.psl.eu
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/cssc.201900358
ChemSusChem
COMMUNICATION
Table 1. Precatalyst screening.[a]
was required but no improvement was observed in terms of
diastereoselectivity (88:12 dr) (Table 1, entry 2).
OH
O
O
O
Cat. (S/C = 200)
OMe
OMe
HCO2H/Et3N (5:2)
CH2Cl2, 30 °C
Although all tested rhodium complexes (R,R)-A–(R,R)-E showed
comparable results in terms of yields and stereoinduction, the
newly prepared complex (R,R)-E gave the highest yield (94%)
and the best level of diastereoselectivity (93:7) in favor of the
syn 1,2-diol 2a (Table 1, entry 6). Therefore, rhodium complex
(R,R)-E was used for further screening of the reaction
parameters and the influence of greener solvents was next
investigated (Figure 4). The results obtained in toluene, i-PrOH,
AcOEt and dimethyl carbonate (DMC) matched those previously
observed in CH2Cl2 in terms of yields but not for the de values
which were higher (88-90% de vs 86% de in CH2Cl2). The neat
reaction gave high yield and enantiomeric excess, but a lower
diastereoselectivity (62% de). Interestingly, the use of the
OMe
OMe
rac-1a
2a
dr [syn/anti][c]
Entry
Cat.
t [h]
yield [%][b]
eesyn [%][d]
1
2[e]
(R,R)-A
(R,R)-A
(R,R)-B
(R,R)-C
(R,R)-D
(R,R)-E
1
91
90
89
89
92
94
91:9
88:12
91:9
91:9
89:11
93:7
99
99
99
99
99
>99
22
1
3
4
3
5
3
6
3
[a] Conditions: 1a (0.8 mmol), [Rh] complex (0.5 mol%), HCO2H/Et3N (5:2)
(134 µL, 2 equiv), CH2Cl2 (4.0 mL) at 30 °C, full conversion. [b] Isolated yields.
[c] Determined by 1H NMR of the crude product after the ATH reaction. [d]
Determined by HPLC analysis using a chiral stationary phase. [e] The reaction
was carried out at 0 °C.
ecofriendly
solvent
2-MeTHF
resulted
in
a
high
diastereoselectivity (94% de) affording a satisfying 93% yield of
2a. Aiming at ever greener procedures, we next sought to
perform the reaction in aqueous media and we chose to use a
1:3 mixture of 2-MeTHF/H2O with sodium formate as the
hydrogen source. These conditions did not allow a complete
conversion (58% yield) but addition of 0.2 equiv of CTAB
(cetyltrimethylammonium bromide) as a surfactant resulted in
82% yield of 2a. A higher yield of 90% could be reached when
switching the reaction temperature from 30 °C to 40 °C whereas
increasing the amount of water in the solvent mixture (from 2-
MeTHF/H2O 1:3 to 1:6) had no significant effect. We next
performed the reaction in water alone as a solvent under
otherwise identical conditions (Figure 5).
We first examined the catalytic activity of complexes (R,R)-A–
(R,R)-E in the asymmetric reduction of methyl 2-methoxy-3-oxo-
3-phenylpropanoate rac-1a. The ATH/DKR of rac-1a was initially
performed in dichloromethane at 30 °C with 0.5 mol% of the Rh
complexes (R,R)-A–(R,R)-E and a HCO2H/Et3N (5:2) azeotropic
mixture as the hydrogen source (Table 1). Under these
conditions, high yields (89–94%) and levels of diastereoselection
(88:12 to 93:7 dr) were observed for the corresponding syn α-
methoxy β-hydroxyester 2a which was obtained with an
excellent enantioselectivity (99% ee). When the reaction was
carried out at 0 °C with complex (R,R)-A, a longer reaction time
'#!"
$$"
$&"
$%"
$$"
$$"
!!"
$$"
$("
$$"
$)"
$$"
$$"
$!"
$$"
$)"
$$"
$("
$$"
$*"
$!"
'!!"
&!"
%!"
$!"
#!"
!"
$%"
$%"
$&"
$("
$("
!!"
!#"
,*"4!"#?$#%8"-"
!&"
()*+,"-."/011/?@A=2"4#"*56)78"
BC"D6EF3GA3BA."=!">0"
)&"
'!"
()*+,"-."/01123"4&"*56)78"
09:;"4!<#"*56)78."=!">0"
()*+,"-."/01123"4&"*56)78"
09:;"4!<#"*56)78."$!">0"
()*+,"-."/01123"4&"*56)7<8"
BC"D6EF3GA3BA."=!>0"
**"-"
Reaction conditions: 1a (0.8 mmol), (R,R)-E (0.5 mol%), HCO2H/Et3N 5:2 (2 equiv) or HCO2Na (8 equiv), solvent (4.0 mL), 30 °C or 40 °C, 3-40 h.
Figure 4. Optimization of the reaction conditions for the ATH of 1a with (R,R)-E.
This article is protected by copyright. All rights reserved.

10.1002/cssc.201900358
ChemSusChem
COMMUNICATION
Table 2. Substrate scope.
+'*"
&&"
&%"
!%"
&&"
&("
,-../,%"1234567"
&&"
&("
&&"
&("
&&"
&("
(R,R)-E (0.5 mol%), HCO2H/Et3N (5:2)
OH
O
O
O
,-../0"1234567"
8529:;<="*>'"23456>"-?@A"
:2"BCDE;0EFG"<"
+**"
!*"
(*"
%*"
'*"
*"
&'"
2-MeTHF, 30 °C
!$"
R
OMe
R
OMe
)#"
or
22<"
OMe
OMe
(R,R)-E (0.5 mol%), HCO2Na (5 equiv)
CTAB (0.2 equiv), H2O, 40 °C
8529:"<="*>'"23456>"HIH"
#("
2a-2m
rac-1a-1m
entry/ATH product 2[a],[b]
t
yield
[%][c]
dr
eesyn
[h]
syn/anti[d]
[%][e]
!"
#"
#"
#"
$"
OH
O
5
4
93
92
97:3
98:2
99
>99
1/2a
2/2b
OMe
OMe
Figure 5. Optimization of the reaction conditions in water at 40 °C with (R,R)-E.
OH
O
7
6
80
84
97:3
97:3
>99
>99
OMe
OMe
In that case, a lower yield was obtained (84%), however, we
found the amount of sodium formate to be essential for the
asymmetric reduction, because decreasing the amount to 5
equiv provided a high yield of 92% whereas the use of 3 equiv
afforded 2a in only 83% yield (Figure 5). It should be noted that
lowering the catalyst loading to 0.25 mol% resulted only in
longer reaction times with no beneficial impact on the
stereoselectivity of the reduction. On the other hand, incomplete
conversions were observed when SDS (sodium dodecyl sulfate)
was used as a surfactant, or when ammonium formate acted as
the hydrogen source. From these results, 2-MeTHF and water
were selected as greener solvents for the remainder of the study
and the optimized reaction conditions were set as follows: 2a,
(R,R)-E (S/C 200), HCO2H/Et3N (5:2) (2.0 equiv), 2-MeTHF,
30 °C, or 2a, (R,R)-E (S/C 200), HCO2Na (5.0 equiv), H2O,
CTAB (0.2 equiv), 40 °C. With these optimized conditions in
hand, we then investigated the scope of the Rh-catalyzed
ATH/DKR of α-methoxy β-ketoesters with a series of variously
substituted aryl ketones 1b–1m. We first studied the asymmetric
reduction of substrates 1b–1f having electron-donating
substituents on the aromatic ring. Compounds bearing methyl,
methoxy or benzyloxy substituents on the benzene core at the
Me
OH
O
8
6
80
83
96:4
97:3
>99
>99
MeO
3/2c
4/2d
OMe
OMe
OH
O
45
6
82
85
96:4
96:4
>99
>99
OMe
OMe
MeO
OH
O
8
24
92
93
97:3
98:2
>99
>99
OMe
5/2e
6/2f
OMe
BnO
OH
O
14
24
83
80
95:5
96:4
99
>99
MeO
OMe
OMe
OMe
OH
O
7
6
68
73
98:2
98:2
>99
>99
7/2g
8/2h
9/2i
OMe
OMe
F
OH
O
8
24
80
89
97:3
95:5
>99
>99
OMe
meta
or
para
positions
afforded
high
levels
of
OMe
F3C
diastereoselectivities, from 95:5 to 98:2 dr, with excellent ee
values observed in all cases (Table 2, entries 2-6). Substrates
1g–1j containing electron-withdrawing groups on the benzene
ring such as fluoro, trifluoromethyl or bromo substituents, were
investigated as well, and displayed good to high yields (68–97%),
high levels of diastereocontrol (95:5 to 99:1 dr) and excellent
enantioselectivities (>99% ee) (Table 2, entries 7–10).
Interestingly, investigation of heteroaromatic substrates 1k–1l
resulted in almost perfect diastereoselectivities (99:1 to >99:1 dr)
and excellent enantioselectivities (Table 2, entries 11 and 12,
>99% ee). To complete the substrate scope, the sterically
demanding compound 1m having an ortho-substituted phenyl
group was submitted to the ATH conditions and delivered the
syn alcohol in good yield, high diastereoselectivy and good
enantioselectivity in water, whereas the reaction was sluggish in
2-MeTHF and gave a lower yield (Table 2, entry 13). This study
showed that homogeneously high levels of stereoselectivity
were observed both in water in open flask and in 2-MeTHF,
whereas higher yields were achieved in water in several
instances (Table 2, entries 7-10 and 12-13). It should be noted
that the methyl protecting group of compounds 2 could be
removed to provide the corresponding syn-1,2-diols.[2a]
OH
O
22
4
82
97
97:3
96:4
>99
>99
OMe
OMe
Br
OH
O
8
4
68
92
99:1
96:4
>99
>99
10/2j
11/2k
12/2l
13/2m
Br
OMe
OMe
OH
O
14
6
91
88
>99:1
>99:1
>99
>99
OMe
S
OMe
OH
O
10
4
86
98
99:1
>99:1
>99
>99
OMe
O
OMe
MeO
OH O
111
5
67
81
96:4
98:2
88
88
OMe
OMe
[a] Conditions A: 1 (0.8 mmol), (R,R)-E (0.5 mol%), HCO2H/Et3N (5:2) (134 µL,
2 equiv), 2-MeTHF (4.0 mL) at 30 °C, full conversion. [b] Conditions B: 1 (0.6
mmol), (R,R)-E (0.5 mol%), HCO2Na (5.0 equiv), H2O (1.5 mL), CTAB (0.2
equiv), 40 °C, full conversion. [c] Isolated yields. [d] Determined by 1H NMR of
the crude product after the ATH reaction. [e] Determined by HPLC analysis
using a chiral stationary phase.
This article is protected by copyright. All rights reserved.

10.1002/cssc.201900358
ChemSusChem
COMMUNICATION
Finally, a scale-up experiment performed on compound 1a (1.25
g, 6.0 mmol) in water delivered the reduced α-methoxy β-
hydroxyester 2a in 88% yield and the same high level of
stereoselectivity as on a 0.6 mmol scale, demonstrating the
usefulness of the procedure.
ParisTech, Paris) and to C. Fosse for the mass spectrometry
analysis (Chimie ParisTech, Paris).
Keywords: asymmetric catalysis • hydrogen transfer • reduction
• rhodium • water
In conclusion, we have prepared a new rhodium catalyst having
an
electron-deficient
diamine
ligand
carrying
a
[1]
a) H. C. Kolb, M. S. VanNieuwenhze, K. B. Sharpless, Chem. Rev.
1994, 94, 2483; b) Y. Shi, Acc. Chem. Res. 2004, 37, 488; c) T. Ikariya,
K. Murata, R. Noyori, Org. Biomol. Chem. 2006, 4, 393; d) G. Guillena,
C. Nájera, D. Ramón, Tetrahedron: Asymmetry 2007, 18, 2249; e) F.
Tanaka, C. F. Barbas III, in Enantioselective Organocatalysis, Reaction
and Experimental Procedures (Ed.: P. I. Dalko), Wiley-VCH, Weinheim,
2007, pp. 19–55; f) P. Jiao, M. Kawasaki, H. Yamamoto, Angew. Chem.
2009, 121, 3383; Angew. Chem. Int. Ed. 2009, 48, 3333.
pentafluorobenzenesulfonyl substituent. The novel fully
characterized Rh-complex is not sensitive to water or air, is
convenient to handle and was efficiently used for the asymmetric
transfer hydrogenation of α-methoxy β-keto esters with either
HCO2H/Et3N (5:2) at a low catalyst loading in an environmentally
sound solvent, 2-MeTHF, or with HCO2Na in water in open flask.
This catalytic atom-economical ATH reaction proceeds in water
[2]
a) S. E. Denmark, W.-J. Chung, Angew. Chem. 2008, 120, 1916;
Angew. Chem. Int. Ed. 2008, 47, 1890; b) S. E. Denmark, W.-J. Chung,
J. Org. Chem. 2008, 73, 4582; c) S. M. Lim, N. Hill, A. G. Myers, J. Am.
Chem. Soc. 2009, 131, 5763; d) K. M. Steward, J. S. Johnson, Org.
Lett. 2010, 12, 2864; e) S.-M. Son, H.-K. Lee, J. Org. Chem. 2013, 78,
8396; f) S.-M. Son, H.-K. Lee, J. Org. Chem. 2014, 79, 2666; g) N.
Alnafta, J. P. Schmidt, C. L. Nesbitt, C. S. P. McErlean, Org. Lett. 2016,
18, 6520; h) L. Fang, S. Liu, L. Han, H. Li, F. Zhao, Organometallics
2017, 36, 1217.
using
a
dynamic kinetic resolution process affording
monodifferentiated β-hydroxyester derivatives in high yields (up
to 98%), high levels of diastereoselection (up to >99:1), and
excellent ee values (up to >99%).
Experimental Section
[3]
a) R. Noyori, M. Tokunaga, M. Kitamura, Bull. Chem. Soc. Jpn. 1995,
68, 36; b) S. Caddick, K. Jenkins, Chem. Soc. Rev. 1996, 25, 447; c) R.
S. Ward, Tetrahedron: Asymmetry 1995, 6, 1475; d) R. Stürmer, Angew.
Chem. 1997, 109, 1221; Angew. Chem. Int. Ed. 1997, 36, 1173; e) M. T.
El Gihani, J. M. J. Williams, Curr. Opin. Chem. Biol. 1999, 3, 11; f) V.
Ratovelomanana-Vidal, J.-P. Genêt, Can. J. Chem. 2000, 851, 846; g)
F. F. Huerta, A. B. E. Minidis, J.-E. Bäckvall, Chem. Soc. Rev. 2001, 30,
321; h) K. Faber, Chem. Eur. J. 2001, 7, 5005; i) O. Pàmies, J.-E.
Bäckvall, Chem. Rev. 2003, 103, 3247; j) H. Pellissier, Tetrahedron
2003, 59, 8291; k) N. J. Turner, Curr. Opin. Chem. Biol. 2004, 8, 114; l)
E. Vedejs, M. Jure, Angew. Chem. 2005, 117, 4040; Angew. Chem. Int.
Ed. 2005, 44, 3974; m) B. Martín-Matute, J.-E. Bäckvall, Curr. Opin.
Chem. Biol. 2007, 11, 226; n) H. Pellissier, Tetrahedron 2008, 64,
1563; o) H. Pellissier, Tetrahedron 2011, 67, 3769; p) P.-G. Echeverria,
T. Ayad, P. Phansavath, V. Ratovelomanana-Vidal, Synthesis 2016, 48,
2523.
General procedure for the asymmetric transfer hydrogenation of
compounds 1a-1m in 2-MeTHF: a round-bottomed tube equipped with
a balloon of argon was charged with α-methoxyl β-keto ester 1 (0.8
mmol) and the rhodium complex (R,R)-E (4.0 µmol, 0.5 mol%). The
solids were subjected to three vacuum/argon cycles before anhydrous 2-
MeTHF (4.0 mL) was added. The mixture was stirred at rt for 3-5 min,
and the tube was transferred into
a 30 °C oil bath, before the
HCO2H/Et3N (5:2) azeotropic mixture (134 µL, 1.6 mmol, 2.0 equiv) was
added dropwise. After complete consumption of the starting material
(monitored by TLC or 1H NMR), the reaction mixture was concentrated
under vacuum, quenched with sat. NaHCO3, and extracted with CH2Cl2.
The combined organic layers were washed with brine, dried (MgSO4),
filtered and concentrated under vacuum. The conversion and
diastereomeric ratio were determined by 1H NMR analysis of the crude
product. After filtration of the crude product on silica gel, the enantiomeric
excess was determined by HPLC analysis (CHIRALPAK IA, IB, IC or IE
column).
[4]
a) G. Zassinovich, G. Mestroni, S. Gladiali, Chem. Rev. 1992, 92, 1051;
b) C. F. de Graauw, J. A. Peters, H. van Bekkum, J. Huskens,
Synthesis 1994, 1007; c) R. Noyori, S. Hashiguchi, Acc. Chem. Res.
1997, 30, 97; d) M. J. Palmer, M. Wills, Tetrahedron: Asymmetry 1999,
10, 2045; e) O. Pàmies, J.-E. Bäckvall, Chem. Eur. J. 2001, 7, 5052; f)
K. Everaere, A. Mortreux, J.-F. Carpentier, Adv. Synth. Catal. 2003,
345, 67; g) S. Gladiali, E. Alberico, Chem. Soc. Rev. 2006, 35, 226; h)
S. M. Joseph, J. S. Samec, J.-E. Bäckvall, P. G. Andersson, P. Brandt,
Chem. Soc. Rev. 2006, 35, 237; i) Ikariya, T.; Blacker, A. J. Acc. Chem.
Res. 2007, 40, 1300; j) A. J. Blacker, in Handbook of Homogeneous
Hydrogenation (Eds.: J. G. de Vries, C. J. Elsevier), Wiley-VCH,
Weinheim, 2007, pp. 1215–1244; k) C. Wang, X. Wu, J. Xiao, Chem.
Asian J. 2008, 3, 1750; l) T. Ikariya, Bull. Chem. Soc. Jpn. 2011, 84, 1;
m) A. Bartoszewicz, N. Ahlsten, B. Martín-Matute, Chem. Eur. J. 2013,
19, 7274; n) T. Slagbrand, H. Lundberg, H. Adolfsson, Chem. Eur. J.
2014, 20, 16102; o) B. Štefane, F. Požgan, Catal. Rev. 2014, 56, 82; p)
D. Wang, D. Astruc, Chem. Rev. 2015, 115, 6621; q) F. Foubelo, C.
Nájera, M. Yus, Tetrahedron: Asymmetry 2015, 26, 769; r) T. Ayad, P.
Phansavath, V. Ratovelomanana-Vidal, Chem. Rec. 2016, 16, 2754; s)
Matsunami, A.; Kayaki, Y. Tetrahedron Lett. 2018, 59, 504.
General procedure for the asymmetric transfer hydrogenation of
compounds 1a-1m in water: a round-bottomed tube was charged with
α-methoxyl β-keto ester 1 (0.6 mmol), sodium formate (3.0 mmol),
cetyltrimethylammonium bromide (0.12 mmol, 20 mol%), the rhodium
complex (R,R)-E (3.0 µmol, 0.5 mol%), water (1.5 mL), and the mixture
was stirred at 40 °C. After complete consumption of the starting material
(monitored by TLC), the reaction mixture was extracted with 2-MeTHF,
the combined organic layers were washed with brine, dried (MgSO4),
filtered and concentrated under vacuum. The conversion and
diastereomeric ratio were determined by 1H NMR analysis of the crude
product. After filtration of the crude product on silica gel, the enantiomeric
excess was determined by HPLC analysis (CHIRALPAK IA, IB, IC or IE
column).
Acknowledgements
[5]
a) D. Cartigny, K. Püntener, T. Ayad, M. Scalone, V. Ratovelomanana-
Vidal, Org. Lett. 2010, 12, 3788; b) L. Monnereau, D. Cartigny, M.
Scalone, T. Ayad, V. Ratovelomanana-Vidal, Chem. Eur. J. 2015, 21,
11799.
This work was supported by the Ministère de l'Education
Nationale, de l'Enseignement Supérieur et de la Recherche
(MENESR) and the Centre National de la Recherche
Scientifique (CNRS). We acknowledge the China Scholarship
Council (CSC) for a grant to B. H. and L.-S. Z. B. H. and L.-S. Z.
contributed equally. We thank C. Férard for technical assistance.
We are grateful to G. Gontard for the X-ray analysis (Sorbonne
Université, Paris), to M.-N. Rager for the NMR analysis (Chimie
[6]
[7]
J. Li, Z. Lin, Q. Huang, Q. Wang, L. Tang, J. Zhu, J. Deng, Green
Chem. 2017, 19, 5367.
a) M. E. Eissen, J. O. Metzger, E. Schmidt, U. Schneidewind, Angew.
Chem. 2002, 114, 402; Angew. Chem. Int. Ed. 2002, 41, 414; b) P. T.
Anastas, J. C. Warner, Green Chemistry: Theory and Practice, Oxford
University Press, New York, 1998, p. 15.
This article is protected by copyright. All rights reserved.

10.1002/cssc.201900358
ChemSusChem
COMMUNICATION
[8]
a) P.-G. Echeverria, C. Férard, P. Phansavath, V. Ratovelomanana-
Vidal, Catal. Comm. 2015, 62, 95; b) L.-S. Zheng, Q. Llopis, P.-G.
Echeverria, C. Férard, G. Guillamot, P. Phansavath, V.
Ratovelomanana-Vidal, J. Org. Chem. 2017, 82, 5607; c) L.-S. Zheng,
C. Férard, P. Phansavath, V. Ratovelomanana-Vidal, Chem. Commun.
2018, 54, 283.
[9]
D. S. Matharu, D. J. Morris, A. M. Kawamoto, G. J. Clarkson, M. Wills,
Org. Lett. 2005, 7, 5489.
[10] CCDC-1894366 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge
Crystallographic
Data
Centre
via
http://www.ccdc.cam.ac.uk/data_request/cif.
This article is protected by copyright. All rights reserved.

10.1002/cssc.201900358
ChemSusChem
COMMUNICATION
COMMUNICATION
OH
O
O
O
cat. (0.5 mol%), HCO2H/Et3N (5:2)
2-MeTHF, 30 °C
cat.:
Bin He, Long-Sheng Zheng, Phannarath
Phansavath* and Virginie
Ratovelomanana-Vidal*
R
OMe
R
OMe
or
Rh
OMe
13 examples
up to 98% yield
95:5 to >99:1 dr
up to >99% ee
OMe
Cl
cat. (0.5 mol%), HCO2Na (5 equiv)
CTAB (0.2 equiv), H2O, 40 °C
O
S
N
N
H
C6F5
Page No. – Page No.
O
Ph
Ph
Novel Rh(III)-Catalyzed Asymmetric
Transfer Hydrogenation of α-Methoxy
β-Ketoesters via DKR in Water:
Toward a Greener Procedure
The asymmetric reduction of α-methoxy β-ketoesters through transfer
hydrogenation using a new rhodium(III) complex is reported. The reaction was
efficient in 2-MeTHF with formic acid/triethylamine or in water with sodium formate.
The corresponding syn α-methoxy β-hydroxyesters were obtained with high
diastereoselectivities and excellent levels of enantioselectivity via a dynamic kinetic
resolution process.
This article is protected by copyright. All rights reserved.