Rh-catalyzed asymmetric hydrogenation of α-aryl-β-alkylvinyl esters with chiral ferrocenylphosphine-phosphoramidite ligand

Article abstract of DOI:10.1016/j.tetlet.2020.152763

An enantioselective Rh-catalyzed hydrogenation of E/Z mixtures of trisubstituted vinyl esters has been disclosed. With a combination of [Rh(COD)₂]BF₄ and a structurally fine-tuning chiral ferrocenylphosphine-phosphoramidite ligand as the catalyst, a variety of E/Z mixtures of α-aryl-β-alkylvinyl esters have been successfully hydrogenated in high yields and with good to high enantioselectivities (up to 96% ee). The presence of a small amount of ^tBuOH proved to be beneficial to improve the hydrogenation outcome.

Full text of DOI:10.1016/j.tetlet.2020.152763

Tetrahedron Letters 65 (2021) 152763
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Rh-catalyzed asymmetric hydrogenation of
a-aryl-b-alkylvinyl esters
with chiral ferrocenylphosphine-phosphoramidite ligand
b,
Chao Dong a,b, Dao-Sheng Liu a, Lei Zhang a, , Xiang-Ping Hu
⇑
⇑
a School of Petrochemical Engineering, Liaoning Shihua University, Fushun 113001, China
b Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
a r t i c l e i n f o
a b s t r a c t
Article history:
An enantioselective Rh-catalyzed hydrogenation of E/Z mixtures of trisubstituted vinyl esters has been
disclosed. With a combination of [Rh(COD)2]BF4 and a structurally fine-tuning chiral ferrocenylphos-
phine-phosphoramidite ligand as the catalyst, a variety of E/Z mixtures of a-aryl-b-alkylvinyl esters have
been successfully hydrogenated in high yields and with good to high enantioselectivities (up to 96% ee).
The presence of a small amount of tBuOH proved to be beneficial to improve the hydrogenation outcome.
Ó 2021 Elsevier Ltd. All rights reserved.
Received 6 November 2020
Revised 12 December 2020
Accepted 15 December 2020
Available online 6 January 2021
Keywords:
Asymmetric catalysis
Rhodium
Hydrogenation
Chiral ligand
Vinyl ester
Introduction
Goo b en et al. described their study on the hydrogenation of E/Z
mixtures of
a-alkyl-b-methylvinyl esters B, giving an ee-value of
Catalytic asymmetric hydrogenation represents one of the most
efficient methods for the enantioselective synthesis of optically
up to 98% in the case of the
recently, Cadierno and Pizzano disclosed that the Rh catalysts bear-
ing chiral phosphine-phosphite ligands were efficient to the hydro-
a
-methyl-substituted ones [7]. More
active compounds.1 Various functionalized olefins including
a- or
b-dehydroamino acid derivatives,
conates and so on can be hydrogenated in excellent yields and
enantioselectivities under the catalysis of various catalysts deco-
a
-enamides,
a
-enol esters, ita-
genation of various trisubstituted vinyl esters, including
dialkyl (C), -alkyl-b-aryl (D), and ,b-diarylvinyl esters (E) [6–
8]. Unexpectedly, less success in the catalytic asymmetric hydro-
genation of -aryl-b-alkylvinyl esters (F) has been disclosed in
a, b-
a
a
rated with
a
wide diversity of chiral phosphorus-containing
a
ligands [1,2]. In contrast, the catalytic asymmetric hydrogenation
of trisubstituted vinyl esters remains underdeveloped (Scheme 1)
[3]. In comparison with the widely studied a,a-disubstituted vinyl
the literature. The development of an efficient catalytic system to
overcome this unmet challenge is therefore highly desirable.
In the past decade, we and other groups have reported a series
of structurally modular chiral phosphine-phosphoramidite ligands
[9,10]. Due to its demonstrated efficacy in the Rh-catalyzed asym-
metric hydrogenation of various functionalized olefins, we envi-
sioned that this ligand class may be also suitable to the Rh-
esters, the inclusion of a substituent in the b-position of vinyl ester
increases the olefin substitution, thus leading to a reduced reactiv-
ity towards the hydrogenation. Furthermore, the trisubstituted
vinyl ester is normally obtained as a E/Z mixture, which greatly
limited its application in the catalytic asymmetric hydrogenation
as the enantioselectivity of the hydrogenation may be critically
dependent on the olefin configuration [3,4] As a result, there are
only a few successful examples on the hydrogenation of trisubsti-
tuted vinyl esters in the literature (Scheme 1a) [5]. In 1999, Zhang
et al. reported a highly enantioselective hydrogenation of cyclic
enol acetates A with Rh/PennPhos catalytic system [6]. In 2012,
catalyzed asymmetric hydrogenation of
As a result, herein we reported an enantioselective Rh-catalyzed
hydrogenation of -aryl-b-alkylvinyl esters with a structurally
a-aryl-b-alkylvinyl esters.
a
fine-tuning chiral ferrocenylphosphine-phosphoramidite ligand,
in which full conversions and up to 96% were achieved.
We initially tested the feasibility of using chiral phosphine-
phosphoramidite ligands for the Rh-catalyzed asymmetric hydro-
genation of trisubstituted vinyl esters. Different chiral phos-
phine-phosphoramidite ligands were screened with
mixture of 1-phenylprop-1-en-1-yl acetate 1a at a ratio of 3.35/1
as the substrate. The hydrogenation was performed in CH2Cl2 at
a E/Z
⇑
Corresponding authors.
E-mail addresses: lnpuzhanglei@163.com (L. Zhang), xiangping@dicp.ac.cn (X.-P.
Hu).
https://doi.org/10.1016/j.tetlet.2020.152763
0040-4039/Ó 2021 Elsevier Ltd. All rights reserved.

C. Dong, Dao-Sheng Liu, L. Zhang et al.
Tetrahedron Letters 65 (2021) 152763
a) Successful trisubstituted vinyl esters in previous works:
OAc
version and with an enantioselectivity of 79% ee (entry 1 versus
entry 2). Further screening of ferrocenylphosphine-phospho-
Ar
Alkyl
Ar
ramidite ligands disclosed that ligand L2b bearing
a
3,30-
dimethyl-1,10-binaphthyl moiety was the most promising, which
gave the hydrogenation product in full conversions and with 83%
ee (entry 3). The nature of solvent showed great effect in the
hydrogenation performance, and ClCH2CH2Cl proved to be the best
choice in term of the enantioselectivity (entries 7–11). When the
Alkyl
OCOR
Alkyl
OAc
Alkyl
OBz
Ar
OCOR
( )n
A
D
E
B
C
b) This work:
Ar
*
Ar
[Rh]/L*
Alkyl
Alkyl
i
AcO
up to 97% ee
AcO
reaction was performed in PrOH, extremely low conversion was
F
observed (entry 11). An attempt to further improve the hydrogena-
tion performance by optimizing the H2 pressure or reaction tem-
perature failed (entries 12–15). During the optimization of the
hydrogenation conditions, an unusual phenomenon was observed
that the present of a small amount of protic solvent could improve
the enantioselectivity (entries 16–18). After examining a series of
protic additives, tBuOH was found to be the best choice (entry
17). The subsequent investigation on the amount of tBuOH dis-
closed that the addition of 50 uL of tBuOH led to the best enantios-
electivity without any compromise to the reactivity (entries 19–
Scheme 1. Rh-catalyzed asymmetric hydrogenation of trisubstituted vinyl esters.
room temperature for 24 h under a H2 pressure of 20 bar in the
presence of 1 mol% of Rh-catalyst prepared in situ from [Rh
(COD)2]BF4 and 1.1 equiv of chiral ligand, and some representative
results are summarized in Table 1. The results disclosed that the
structure of phosphine-phosporamidite ligands significantly
affected the reactivity and enantioselectivity (entries 1–6). To our
surprise, 1-phenylethylamine-derived ligand L1 displayed no
activity towards this hydrogenation, while the structurally similar
ferrocenylphosphine-phosphoramidite ligand L2a led to a full con-
t
21). We reasoned that the presence of a small amount of BuOH
may facilitate the liberation of the hydrogenation product from
the central metal by the competitive O-coordination of tBuOH
Table 1
Optimization of hydrogenation conditions.a
[Rh(COD)2]BF4 (1 mol%)
L*
H2, additives (30 uL)
(1.1 mol%)
Ph
OAc
Ph
OAc
2a
1a
solvent (2 mL), temp, 24 h
(E/Z = 3.35/1)
R
R
N
O
P
O
P
PPh2
O
N
N
P
O
PPh2
O
O
Fe
PPh2
Fe
R
L1
)
(Rc,Ra)-PEAPhos (
L3
)
(Rc,Sp,Ra)-(
L2
)
(Sc,Rp,Sa)-PPFAPhos (
L2a
L2b
: R = Me;
: R = H;
: R = I
L3a
: R = H;
: R = Me
L2c
L3b
Entry
L*
solvent
additive
H2 (bar)
Temp. (oC)
Conv.b (%)
eec (%)
1
2
3
4
5
6
7
8
L1
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
ClCH2CH2Cl
CF3CH2OH
THF
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
20
20
20
20
20
20
20
20
20
20
20
10
30
20
20
20
20
20
20
20
20
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
10
50
rt
rt
rt
rt
rt
rt
<10
>99
>99
<10
>99
>99
>99
65
–
L2a
L2b
L2c
L3a
L3b
L2b
L2b
L2b
L2b
L2b
L2b
L2b
L2b
L2b
L2b
L2b
L2b
L2b
L2b
L2b
79
83
–
69
74
85
64
17
7
9
50
50
10
11
12
13
14
15
16
17
18
19
20
21
EtOH
iPrOH
<10
>99
>99
90
>99
>99
>99
>99
>99
>99
90
–
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
81
82
83
35
85
87
81
85
91
86
CF3CH2OH (30 uL)
tBuOH (30 uL)
AcOH (30 uL)
tBuOH (10 uL)
tBuOH (50 uL)
tBuOH (70 uL)
a
Reaction conditions: all reactions were carried out with a Rh/Ligands /1a (0.125 mmol) at a ratio of 1:1.1:100 in 2 mL of solvent in the presence of additives under an H2
pressure for 24 h, unless otherwise noted.
b
Conversion was determined by GC.
The ee-value was determined by Chrial GC.
c
2

C. Dong, Dao-Sheng Liu, L. Zhang et al.
Tetrahedron Letters 65 (2021) 152763
[Rh(COD)2]BF4 (1 mol%)
and the product, therefore favorable to the catalyst turnover and
enantioselectivity. However, excess BuOH inhibited the O-coordi-
t
L2b
(1.1 mol%)
H2 (20 bar), tBuOH (0.5 mL)
DCE (20 mL), rt, 24 h
Ph
OAc
(E/Z = 3.35/1)
0.5 g, 2.8 mmol
Ph
OAc
2a
nation of the substrate to the central metal, thus leading to the
decrease in the hydrogenation performance. However, the real role
1a
t
of BuOH is still unclear [9,10].
Having established the optimized conditions, we next exploited
NaOH/MeOH
reflux, 3 h
Ph
3a,
OH
0.36 g
the scope of
a-aryl-b-alkylvinyl acetates. All vinyl acetates were
directly used as a mixture of E/Z-isomers (for the E/Z ratio of each
vinyl ester, see the Supporting Information). The results in
Scheme 2 indicated that the substitution pattern on the phenyl
ring showed some influence on the enantioselectivity. Thus,
orthro-substituted substrate 1b displayed much lower reactivity
towards the hydrogenation in comparison with its meta- and
para-analogues (1c and 1d). The electronic effect and the substitu-
tion pattern at meta- or para-position of the phenyl ring showed an
observable effect in the hydrogenation outcome although all sub-
strates exhibited excellent conversions and good to high enantios-
electivities. Among them, 3-F-substituted substrate 1f gave the
best result of > 99% conversion and 96% ee. Besides the methyl sub-
stituent at the b-position, other aliphatic groups were also toler-
ated. For examples, the hydrogenation of b-Et and b-iPr-
substituted vinyl acetates 1o and 1p led to the corresponding
hydrogenation products 2o and 2p in > 99% conversion with 90%
ee and > 99% conversion with 95% ee, respectively.
To demonstrate synthetic utility of this methodology, a 0.5 g-
scale hydrogenation of 1a was conducted under the optimized con-
ditions, giving 1-phenylpropyl acetate 2a in full conversion. The
further transformation of 2a by the reaction with NaOH/MeOH in
a simple procedure gave rise to the corresponding alcohol 3a in
good yield and with the maintained enantioselectivity (Scheme 3).
In summary, we have realized an enantioselective Rh-catalyzed
93% yield, 92% ee
Scheme 3. Synthetic transformation.
enantioselectivities. Further development and application of this
hydrogenation, and further modification and application of chiral
phosphine-phosphoramidite ligands are still underway.
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
Acknowledgments
Financial supports from the National Natural Science Founda-
tion of China (22071240 and 21772196) are gratefully
acknowledged.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tetlet.2020.152763.
hydrogenation of the E/Z mixtures of
a-aryl-b-alkylvinyl acetates
with a structurally fine-tuning chiral ferrocenylphosphine-phos-
phoramidite ligand developed by ourselves. The addition of a small
amount of tBuOH to the reaction system has been demonstrated to
improve the hydrogenation performance. Under optimized condi-
References
[1] J.G. de Vries, C.J. Elsevier (Eds.), Handbook of Homogeneous Hydrogenation,
Wiley-VCH, Weinheim, 2007.
tions, various
a-aryl-b-alkylvinyl acetates in a form of the E/Z-mix-
[2] (a) For selected reviews, see: R. Noyori, T. Ohkuma Angew. Chem. Int. Ed. 40
(2001) 40;
ture were hydrogenated in excellent yields and good to high
(b) W. Tang, X. Zhang, Chem. Rev. 103 (2003) 3029;
(c) H.-U. Blaser, C. Malan, B. Pugin, F. Spindler, H. Steiner, M. Studer, Adv.
Synth. Catal. 345 (2003) 103;
(d) Y.-G. Zhou, Acc. Chem. Res. 40 (2007) 1357;
R
R
(e) S.J. Roseblade, A. Pfaltz, Acc. Chem. Res. 40 (2007) 1402;
(f) N.B. Johnson, I.C. Lennon, P.H. Moran, J.A. Ramsden, Acc. Chem. Res. 40
(2007) 1291;
(g) C.S. Shultz, S.W. Krska, Acc. Chem. Res. 40 (2007) 1320;
(h) H. Shimizu, I. Nagasaki, K. Matsumura, N. Sayo, T. Saito, Acc. Chem. Res. 40
(2007) 1385;
[Rh(COD)2]BF4 (1 mol%)
L2b
(1.1 mol%)
H2 (20 bar), tBuOH (50 uL)
DCE (2 mL), rt, 24 h
Ar
OAc
1b-p
(E/Z mixture)
Ar
OAc
2b-p
(i) J.-H. Xie, S.-F. Zhu, Q.-L. Zhou, Chem. Rev. 111 (2011) 1713;
(j) Y. Zhu, K. Burgess, Acc. Chem. Res. 45 (2012) 1623;
(k) D.S. Wang, Q.A. Chen, S.M. Lu, Y.G. Zhou, Chem. Rev. 112 (2012) 2557;
(l) D.J. Ager, A.H.M. de Vries, J.G. de Vries, Chem. Soc. Rev. 41 (2012) 3340;
(m) P. Etayo, A. Vidal-Ferran, Chem. Soc. Rev. 42 (2013) 728;
(n) Q.-A. Chen, Z.-S. Ye, Y. Duan, Y.-G. Zhou, Chem. Soc. Rev. 42 (2013) 497;
(o) J.J. Verendel, O. Pàmies, M. Diéguez, P.G. Andersson, Chem. Rev. 114 (2014)
2130;
OAc
OAc
OAc
2b
2c
2d
<10% conv. >99% conv., 88% ee
>99% conv., 84% ee
2e
2f
2g
2h
2i
(R = OMe): >99% conv., 84% ee
(R = F): >99% conv., 96% ee
(R = Cl): >99% conv., 88% ee
(R = Br): >99% conv., 95% ee
(R = CF3): >99% conv., 85% ee
(p) G. Chelucci, S. Baldino, W. Baratta, Acc. Chem. Res. 48 (2015) 363;
(q) R.H. Morris, Acc. Chem. Res. 48 (2015) 1494;
(r) P.J. Chirik, Acc. Chem. Res. 48 (2015) 1687;
R
OAc
(s) Y.Y. Li, S.-L. Yu, W.-Y. Shen, J.-X. Gao, Acc. Chem. Res. 48 (2015) 2587;
(t) Z. Zhang, N.A. Butt, W. Zhang, Chem. Rev. 116 (2016) 14769.
[3] For a review, see: Z. Wang, Z. Zhang, Y. Liu, W. Zhang Chin. J. Org. Chem. 36
(2016) 447.
[4] (a) B.D. Vineyard, W.S. Knowles, M.J. Sabacky, G.L. Bachman, D.J. Weinkauff, J.
Am. Chem. Soc. 99 (1977) 5946;
2j
2k
2l
2m
2n
(R = OMe): >99% conv., 95% ee
(R = F): >99% conv., 89% ee
(R = Cl): >99% conv., 90% ee
(R = Br): >99% conv., 83% ee
(R = CF3): >99% conv., 88% ee
OAc
R
(b) A. Miyashita, H. Takaya, T. Souchi, R. Noyori, Tetrahedron 40 (1984) 1245;
(c) D. Peña, A.J. Minnaard, J.G. de Vries, B.L. Feringa, J. Am. Chem. Soc. 124
(2002) 14552;
(d) J. Chen, W. Zhang, H. Geng, W. Li, G. Hou, A. Lei, X. Zhang, Angew. Chem.
Int. Ed. 48 (2009) 800;
OAc
OAc
(e) S.-F. Zhu, T. Liu, S. Yang, S. Song, Q.-L. Zhou, Tetrahedron 68 (2012) 7685;
(f) J. Jiang, Y. Wang, X. Zhang, ACS Catal. 4 (2014) 1570.
[5] (a) Y. Kuroki, D. Asada, Y. Sakamaki, T. Iseki, Tetrahedron Lett. 41 (2000) 4603;
(b) E.A. Broger, W. Burkart, M. Hennig, M. Scalone, R. Schmid, Tetrahedron:
Asymmetry 9 (1998) 4043;
2p
2o
>99% conv., 95% ee
>99% conv., 90% ee
Scheme 2. Scope of a-aryl-b-alkylvinyl acetates.
3

C. Dong, Dao-Sheng Liu, L. Zhang et al.
Tetrahedron Letters 65 (2021) 152763
(c) L. Pignataro, C. Bovio, M. Civera, U. Piarulli, C. Gennari, Chem. Eur. J. 18
(2012) 10368.
(e) J.-D. Huang, X.-P. Hu, Z.-C. Duan, Q.-H. Zeng, S.-B. Yu, J. Deng, D.-Y. Wang, Z.
Zheng, Org. Lett. 8 (2006) 4367;
[6] Q. Jiang, D. Xiao, Z. Zhang, P. Cao, X. Zhang, Angew. Chem. Int. Ed. 38 (1999)
516.
(f) D.-Y. Wang, X.-P. Hu, J.-D. Huang, J. Deng, S.-B. Yu, Z.-C. Duan, X.-F. Xu, Z.
Zheng, Angew. Chem. Int. Ed. 46 (2007) 7810;
[7] P. Mamone, M.F. Grünberg, A. Fromm, B.A. Khan, L.J. Gooen, Org. Lett. 14 (2012)
3716.
(g) J. Wassenaar, E. Jansen, W.-J. van Zeist, F.M. Bickelhaupt, M.A. Siegler, A.L.
Spek, J.N.H. Reek, Nature Chem. 2 (2010) 417;
[8] (a) P.J. González-Liste, F. León, I. Arribas, M. Rubio, S.E. García-Garrido, V.
Cadierno, A. Pizzano, ACS Catal. 6 (2016) 3056;
(h) X.-M. Zhou, J.-D. Huang, L.-B. Luo, C.-L. Zhang, X.-P. Hu, Z. Zheng, Org.
Biomol. Chem. 8 (2010) 2320;
(b) F. León, P.J. González-Liste, S.E. García-Garrido, I. Arribas, M. Rubio, V.
Cadierno, A. Pizzano, J. Org. Chem. 82 (2017) 5852.
[9] (a) For selected reviews, see: F. Boeda, T. Beneyton, C. Crevisy Mini-Rev. Org.
Chem. 5 (2008) 96;
(i) X. Zhang, B. Cao, S. Yu, X. Zhang, Angew. Chem. Int. Ed. 49 (2010) 4047;
(j) S.H. Chikkali, R. Bellini B. de Bruin J.I. van der Vlugt J.N.H. Reek,, J. Am.
Chem. Soc. 134 (2012) 6607;
(k) C.-J. Hou, Y.-H. Wang, Z. Zheng, J. Xu, X.-P. Hu, Org. Lett. 14 (2012) 3554;
(l) C. Schmitz, K. Holthusen, W. Leitner, G. Franciò, ACS Catal. 6 (2016) 1584;
(m) C. Chen, S. Jin, Z. Zhang, B. Wei, H. Wang, K. Zhang, H. Lv, X.-Q. Dong, X.
Zhang, J. Am. Chem. Soc. 138 (2016) 9017;
(n) C. You, B. Wei, X. Li, Y. Yang, Y. Liu, H. Lv, X. Zhang, Angew. Chem. Int. Ed.
55 (2016) 6511;
(o) C. You, S. Li, X. Li, J. Lan, Y. Yang, L.W. Chuang, H. Lv, X. Zhang, J. Am. Chem.
Soc. 140 (2018) 4977;
(b) L. Eberhardt, D. Armspash, J. Harrowfield, D. Matt, Chem. Soc. Rev. 37
(2008) 839;
(c) J. Wassenaar, J.N.H. Reek, Org. Biomol. Chem. 9 (2011) 1704;
(d) C.-J. Hou, X.-N. Liu, Y. Xia, X.-P. Hu, Chin. J. Org. Chem. 32 (2012) 2239;
(e) D. Drommi, C.G. Arena, Curr. Org. Chem. 20 (2016) 2552;
(f) X.-S. Chen, C.-J. Hou, X.-P. Hu, Synth. Commun. 46 (2016) 917.
[10] (a) For selected examples, see: G. Franciò, F. Faraone, W. Leitner Angew.
Chem., Int. Ed. 39 (2000) 1428;
(p) X.-H. Hu, X.-P. Hu, Adv. Synth. Catal. 361 (2019) 5063;
(q) H.-Q. Du, X.-P. Hu, Org. Lett. 21 (2019) 8921;
(b) X.-P. Hu, Z. Zheng, Org. Lett. 6 (2004) 3585;
(c) Y. Yan, X. Zhang, J. Am. Chem. Soc. 128 (2006) 7198;
(d) W. Zhang, X. Zhang, Angew. Chem., Int. Ed. 45 (2006) 5515;
(r) X.-H. Hu, X.-P. Hu, Org. Lett. 21 (2019) 10003.
4