Asymmetric transfer hydrogenation of α-azido acrylates

Article abstract of DOI:10.1016/j.tetlet.2014.11.072

The asymmetric transfer hydrogenation of α-azido acrylates has been explored, a range of α-hydroxy esters are produced with good enantioselectivities (80-90% ee). The reaction was conducted in the wet HCO₂H/NEt₃ with Ru-TsDPEN A.

Full text of DOI:10.1016/j.tetlet.2014.11.072

Tetrahedron Letters 56 (2015) 192–194
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Asymmetric transfer hydrogenation of
a
-azido acrylates
⇑
Yang Ji, Ping Xue, Dan-Dan Ma, Xue-Qiang Li, Peiming Gu, Rui Li
Key Laboratory of Energy Sources & Engineering, State Key Laboratory Cultivation Base of Natural Gas Conversion and Department of Chemistry, Ningxia University,
Yinchuan 750021, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 July 2014
Revised 4 November 2014
Accepted 14 November 2014
Available online 21 November 2014
The asymmetric transfer hydrogenation of
esters are produced with good enantioselectivities (80–90% ee). The reaction was conducted in the wet
HCO2H/NEt3 with Ru-TsDPEN A.
a-azido acrylates has been explored, a range of a-hydroxy
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Asymmetric transfer hydrogenation
a-Hydroxy esters
Azides
Ru-TsDPEN catalyst
Lactates
Enantio-enriched
a
-hydroxy carboxylic acids and their deriva-
transfer hydrogenation of the
commercially available Ru-TsDPEN catalysts A–E (Fig. 1).
The -azido cinnamate 1a was selected for the initial investiga-
a-azido acrylates with the selected
tives are very important precursors for the preparation of a variety
of significant compounds.1 The preparation of them has attracted
broad interest from chemists.2 The most general method toward
a
tion. To our delight, the phenyl lactate 2a was obtained with all the
Ru-TsDPEN catalysts A–E in the HCO2H/NEt3 azeotrope. If a small
amount of water was added, the conversion could be accelerated.
Then all the experiments were conducted with the wet HCO2H/
NEt3 (Table 1). Among the catalysts (3 mol %) examined here,
Ru-TsDPEN (S,S)-A gave the best result, and the phenyl lactate 2a
was obtained in 84% yield with 88% enantioselectivity. The transfer
hydrogenation of 1a with catalyst (R,R)-E produced ester 2a with
the same enantioselectivity, but the yield was slightly lower.
Further optimization with different ratio of HCO2H/NEt3 using
(R,R)-E failed to give better result. Transfer hydrogenation of 1a
at room temperature with (S,S)-A resulted in longer reaction time
and lower conversion. Fortunately, 0.5 mol % of (S,S)-A catalyzed
the reaction well, and the similar enantioselectivity (90% ee) and
yield (84%) were observed. The absolute stereochemistry of 2a
was assigned as the S configuration by comparison of the rotation
them is the catalytic asymmetric reduction of
acids or -keto esters. Following our continuous research on the
reaction of alkenyl azides,3,4 herein we report an efficient prepara-
tion of chiral -hydroxy esters through the asymmetric transfer
hydrogenation of -azido acrylates.
a-keto carboxylic
a
a
a
The reduction of azide to amine5 and the conversion of alkene
to alkane6 could be realized under the hydrogenation conditions.
Therefore, part hydrogenation of an alkenyl azide would afford
two different types of products, known as alkyl azide and enamine.
The alkyl azide would be produced if the hydrogenation of alkene
was preferred over the azido group, and it could be further con-
verted to an amine under the hydrogenation conditions. On the
contrary, enamine would be afforded if reduction of the azido
group was prior to the alkene. The enamine could be easily hydro-
lyzed to a ketone, which would be further converted to an alcohol
under the reducing conditions.6 So if the chiral reductant could
control the order of hydrogenation with good enantioselectivity,
the dominant product would be either the enantio-enriched amine
or the chiral alcohol.
data ([a]
D À13.7) with that of the previous reports ([
a]D +15.5 with
the R-enantiomer).8 The catalytic activities of (S,S)-A and (R,R)-E
are superior to others. This is most likely due to the phenyl side-
arm of the diamine ligand, which stabilizes the active Ru species
so that the longevity of the catalyst gets improved.
The
a-azido acrylates could be easily prepared from the
condensation of aldehydes with the
a
-azido acetate according to
We next explored the scope of the a-azido cinnamates with
the reported procedure.7 We decided to explore the asymmetric
0.5 mol % catalyst A (Table 2). The substrates with electron donat-
ing groups or electron withdrawing groups on the phenyl ring all
proceeded the conversion smoothly, and gave the corresponding
aryl lactates 2b–2h in 81–90% yield with good enantioselectivities
⇑
Corresponding author. Tel.: +86 (951)206 2274; fax: +86 (951)206 2323.
E-mail address: ruili@nxu.edu.cn (R. Li).
http://dx.doi.org/10.1016/j.tetlet.2014.11.072
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

Y. Ji et al. / Tetrahedron Letters 56 (2015) 192–194
193
Ph
Ph
Ph
Ph
Ph
Ph
N
F
F
F
Ph
Ph
Ph
Ph
O
S
H
H
H
H
H
N
N
Cl
Ts
N
N
Cl
Ts
N
F
N
N
Cl
Ts
N
N
Cl
Ts
H
Ru
Ru
Ru
H
H
Ru
Ru
Cl O
Me
Me
Me
Me
Me
O
Me
Me
Me
F
Me
Me
(R,R)-E
(R,R)-C
(S,S)-D
(S,S)-A
(S,S)-B
Figure 1. Ru-complex for asymmetric transfer hydrogenation of 1a.
Table 1
O
O
Optimization of the asymmetric transfer hydrogenation of 1aa
Ru-TsDPEN (S,S)-A
OMe
OMe
O
O
wet HCO2H/NEt3
OH
Ru* cat
OH
3a
∗
O
O
2a (89% ee)
88 %
N3
OH
2a
Scheme 1. Asymmetric transfer hydrogenation of
a
-keto ester 3a.
1a
Entry
Cat
Conditions
Time (h)
Yieldb
eec
a
-hydroxy ester 2i was obtained in only 28% yield with a good
1
2
3
4
5
6
7
8
9
10
(S,S)-A
(S,S)-B
(R,R)-C
(S,S)-D
(R,R)-E
(R,R)-E
(R,R)-E
(R,R)-E
(S,S)-A
(S,S)-A
HCO2H/NEt3 (5:2), 60 °C
HCO2H/NEt3 (5:2), 60 °C
HCO2H/NEt3 (5:2), 60 °C
HCO2H/NEt3 (5:2), 60 °C
HCO2H/NEt3 (5:2), 60 °C
HCO2H/NEt3 (7:2), 60 °C
HCO2H/NEt3 (2:1), 60 °C
HCO2H/NEt3 (5:2), rt
8
8
24
8
28
48
48
72
72
8
84
71
76
53
77
74
80
—
88
control of enantioselectivity (86% ee). Enhancement of the load of
catalyst from 0.5 mol % to 3 mol % did not improve the yield as well
as the enantioselectivity. The isopropyl
prepared, and subjected to the asymmetric transfer hydrogenation
to see if the enantioselectivity could be improved. However no
better result could be obtained with lactate 2j (87% ee), while
the yield was improved to 99%.
82
À71d
74
a-azido cinnamate was
À88d
À86d
À88d
—
HCO2H/NEt3 (5:2), rt
HCO2H/NEt3 (5:2), 60 °C
62
84
89
90e
The asymmetric transfer hydrogenation of an
a-azido b-alkyl-
a
acrylate was also successful, but the -hydroxy ester 2k was
a
Asymmetric hydrogenation of
a-azido cinnamate 1a (101 mg, 0.5 mmol) with
obtained with very moderate yields (41%). The enantioselectivity
(81% ee) of 2k was determined with its benzoate by chiral HPLC.
It should be noted that the S configuration of 2k was also assigned
Ru catalyst (3 mol %) in the presence of wet HCO2H/NEt3 under the conditions
mentioned above.
b
Isolated yield after acidic work up.
Determined by chiral HPLC.
Opposite enantioselectivity of the product was observed.
Reaction with 0.5 mol % catalyst.
c
by comparison of its rotation data ([
a
]D À2.0, c 0.6 in EtOH) to that
d
of the reported result.10
e
It should be noted that generally the corresponding
a
-keto ester
could be found and isolated from the reaction mixture. Asymmet-
ric hydrogenation of -keto ester has been extensively explored,
and generally the -hydroxy ester could be obtained with good
enantioselectivity and yields.11 Herein, the asymmetric transfer
hydrogenation of -keto ester 3a (with the stable enol form,
30.0 mg) with Ru-TsDPEN (S,S)-A under wet HCO2H/NEt3
(80–87% ee). It should be noted here that the enantio-enriched
a
a-hydroxy ester 2e had been obtained from the lipase catalyzed
a
resolution, and was used for the total synthesis of (+)-Pentameth-
ylsalvianolic acid C.9 Asymmetric hydrogenation of the fural
a
substituted
a-azido cinnamate 1i faced a deep embarrassment,
Table 2
Scope of conversion
O
O
O
O
O
O
OH
OH
OH
O
2a, 84% yield, 90% ee
2b, 84% yield, 87% ee
2c, 90% yield, 85% ee
O
O
O
O
O
O
O
O
O
OH
OH
OH
Cl
2d, 84% yield, 84% ee
2e, 82% yield, 80% ee
2f, 81% yield, 85% ee
O
O
O
O
O
O
O
OH
OH
OH
Br
NC
2g, 83% yield, 83% ee
2h, 83% yield, 84% ee
2i, 28% yield, 86% ee
O
O
O
O
OH
OH
2j, 99% yield, 87% ee
2k, 41% yield, 81% ee

194
Y. Ji et al. / Tetrahedron Letters 56 (2015) 192–194
O
O
hydrogenation, and the enantioselectivities were good to excellent.
Further research in our laboratory will focus on the conversion of
-azido acrylates to the enantio-enriched -amino esters.
Ru* cat
R'
R'
∗
R
O
R
O
a
a
N3
OH
1
2
Acknowledgment
Hydrogenation
of azide
Hydrogenation
of ketone
This work was supported by the Ningxia Natural Science
Foundation (NZ13046).
O
O
+ H2O
- NH3
R'
O
R'
O
R
R
Supplementary data
NH2
O
Supplementary data (experimental procedures and spectro-
scopic data and copies of NMR spectra and copies of HPLC spectra
for all the products) associated with this article can be found, in the
online version, at http://dx.doi.org/10.1016/j.tetlet.2014.11.072.
A
B
Scheme 2. A possible mechanism of asymmetric transfer hydrogenation of a-azido
acrylate.
References and notes
azeotrope has been studied (Scheme 1), and the phenyl lactate 2a
(26.7 mg) was obtained with 89% ee in 88% yield, which was
1. A selected review, see: Coppola, G. M.; Schuster, H. F.
a-Hydroxy Acids in
comparable to that of
The preparation of an
compound) by condensation of aldehyde and the
would be more convenient than that of -keto ester (1,2-difunc-
tional compound), though the former is more complex than the
latter in view of their structures. To some extent, this conversion
could be used as a supplement to the asymmetric transfer
a
-azido cinnamate 1a (90% ee, 84% yield).
,b-unsaturated ester (1,3-difunctional
-azido acetate
Enantioselective Synthesis; VCH: Weinheim, 1997.
2. Reviews, see: (a) Ohkuma, T.; Kitamura, M.; Noyori, R. In Catalytic Asymmetric
Synthesis; Ojima, I., Ed., 2nd ed.; Wiley-VCH: New York, 2000; pp 1–110; (b)
Brown, J. M. In Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfalz, A.,
Yamamoto, H., Eds.; Springer: Berlin, 1999; Vol. I, pp 121–182; (c) Tang, W.;
Zhang, X. Chem. Rev. 2003, 103, 3029–3069; (d) Davis, F. A.; Chen, B.-C. Chem.
Rev. 1992, 92, 919.
a
a
a
3. Gu, P.; Su, Y.; Wu, X.-P.; Sun, J.; Liu, W.-Y.; Xue, P.; Li, R. Org. Lett. 2012, 14,
2246–2249.
4. Gu, P.; Wu, X.-P.; Su, Y.; Xue, P.; Li, X.-Q.; Gong, B.-L.; Li, R. Tetrahedron Lett.
2013, 54, 4957–4959.
hydrogenation of
a-keto ester.
From the above experiments and previous literatures,
proposed mechanism is outlined in Scheme 2. The conversion
includes the following three stages: (1) Reduction of the azido
a
5. For an example on the hydrogenation of azide to amine, see: Lin, W.; Zhang, X.;
He, Z.; Jin, Y.; Gong, L.; Mi, A. Synth. Commun. 2002, 32, 3279–3284.
6. For A special issue on asymmetric hydrogenation and asymmetric transfer
hydrogenation in Accounts of Chemical Research, see: Acc. Chem. Res. 2007, 40,
1237–1419.
group of the
a-azido acrylate under the transfer hydrogenation
conditions affords the unstable enamine intermediate A; (2)
7. Preparation of a-azido conjugate esters, see: (a) Stokes, B. J.; Dong, H.; Leslie, B.
E.; Pumphrey, A. L.; Driver, T. G. J. Am. Chem. Soc. 2007, 129, 7500–7501; (b)
O’Brien, A. G.; Levesque, F.; Seeberger, P. H. Chem. Commun. 2011, 2688–2690.
8. For the (R)-2a, [a]D +15.5 (c 1.0, CH2Cl2), see: Killian, J. A.; Cleve, M. D. V.; Shayo,
Y. F.; Hecht, S. M. J. Am. Chem. Soc. 1998, 120, 3032–3042.
9. Alford, B. L.; Hügel, H. M. Org. Biomol. Chem. 2013, 11, 2724–2727.
Hydrolysis of the enamine in the wet HCO2H/NEt3 azeotrope
results in the
tion of the
-hydroxy ester 2 as the final product. The observed enantioselec-
a-keto ester B; (3) Asymmetric transfer hydrogena-
a-keto ester with Ru-TsDPEN efficiently delivers the
a
10. For the (S)-2k, [a]D À5.5 (c 0.92, EtOH), see: Nakajima, M.; Watanabe, B.; Han,
tivity of this process agreed with the asymmetric transfer hydroge-
nation of alkyl/alkyl ketones, which has been extensively discussed
by Martin Wills and co-workers.12
L.; Shimizu, B.; Wada, K.; Fukuyama, K.; Suzuki, H.; Hiratake, J. Bioorg. Med.
Chem. 2014, 22, 1176–1194.
11. (a) Inoguchi, K.; Sakuraba, S.; Achiwa, K. Synlett 1992, 169–178; (b) Benincori,
T.; Brenna, E.; Sannicolò, F.; Trimarco, L.; Antognazza, P.; Cesarotti, E.;
Demartin, F.; Pilati, T. J. Org. Chem. 1996, 61, 6244–6251; (c) Carpentier, J.-F.;
Mortreux, A. Tetrahedron: Asymmetry 1997, 8, 1083–1099; (d) Lightfoot, A.;
Schnider, P.; Pfaltz, A. Angew. Chem., Int. Ed. 1998, 37, 2897–2899; (e) Benincori,
T.; Cesarotti, E.; Piccolo, O.; Sannicolò, F. J. Org. Chem. 2000, 65, 2043–2047.
12. Morris, D. J.; Hayes, A. M.; Wills, M. J. Org. Chem. 2006, 71, 7035–7044.
In conclusion, the preparation of chiral
the asymmetric transfer hydrogenation of
a
-hydroxy esters from
a
-azido acrylates have
been demonstrated, and Ru-TsDPEN complex A is efficient to
catalyze the conversion. The sequenced reaction is combined
with azide reduction/enamine hydrolyzation/asymmetric transfer