Efficient P-Chiral Biaryl Bisphosphorus Ligands for Palladium-Catalyzed Asymmetric Hydrogenation

Article abstract of DOI:10.1002/cjoc.201700645

A series of structurally novel P-chiral biaryl bisphosphorus ligands L1-L5 (BABIBOPs) are developed, providing high efficiency for the first time in palladium-catalyzed asymmetric hydrogenation of β-aryl and β-alkyl substituted β-keto esters. With the Pd-L3 (iPr-BABIBOP) catalyst, a series of chiral β-hydroxyl carboxylic esters are formed in excellent enantioselectivities (up to>99% ee) and yields at catalyst loading as low as 0.01 mol%.

Full text of DOI:10.1002/cjoc.201700645

Efficient P-Chiral Biaryl Bisphosphorus Ligands for Palladium-Catalyzed
Asymmetric Hydrogenation
Wenhao Jiang,a Qing Zhao,b Wenjun Tang*, a,b
a Department of Pharmaceutical Engineering , School of Pharmacy, East China
University of Science and Technology, 130 Mei Long Rd, Shanghai 200037
b State Key Laboratory of Bio-Organic and Natural Products Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling Ling Rd,
Shanghai 200032, E-mail: tangwenjun@sioc.ac.cn
ABSTRACT A series of structurally novel P-chiral biaryl bisphosphorus ligands L1-5 (BABIBOPs) are developed, providing high efficiency for the first time in
palladium-catalyzed asymmetric hydrogenation of β-aryl and β-alkyl substituted β-keto esters. With the Pd-L3 (iPr-BABIBOP) catalyst, a series of chiral β-
hydroxyl carboxylic esters are formed in excellent enantioselectivities (up to >99% ee) and yields at catalyst loading as low as 0.01 mol %.
KEYWORDS biaryl bisphosphorus ligands, asymmetric hydrogenation, enantioselectivity, palladium, P-chiral
Introduction
In contrast to the latest advances in rhodium, ruthenium, and
iridium catalyzed asymmetric hydrogenation, the palladium-
catalyzed asymmetric hydrogenation remains
a
relatively
underdeveloped area.1-3 Excellent enantioselectivities (>99% ee)
were only achieved on a few substrates.2 In particular, palladium-
catalyzed asymmetric hydrogenation of ketones remains a very
difficult area with few successes.3j,3i For example, only a moderate
enantiomeric excess (48%) was observed on palladium-catalyzed
asymmetric hydrogenation of a β-aryl-β-keto ester.3j It is therefore
of significant importance to continue the vigorous research and
development in exploring efficient palladium-catalyzed asymmetric
hydrogenation.
Figure 1 Design of P-chiral biaryl bisphosphorus ligands BABIBOPs
Results and Discussion
Preparation of L1-5 commenced from the known chiral triflate
1,7a a key chiral synthetic unit for various P-chiral phosphorus
ligands.7 Homocoupling of 1 at 4 position would furnish the
skeleton of these ligands. However, many methods including
copper-, palladium- or nickel-catalyzed coupling resulted in
hydrolysis of the triflate as the main side-reaction. We then
decided to convert triflate 1 to the corresponding aryl iodide 2.
Thus, Buchwald-Hartwig amination, Boc deprotection, and
Sandmeyer iodination formed iodide 2 in 33% unoptimized yield
through three steps. Next, the homocoupling of 2 was pursued. It
turned out that the copper-mediated Ullmann-type coupling and
Suzuki-type cross-coupling conditions failed to provide the desired
product largely because of the great steric hindrance encountered
in this transformation. After many experimentations, we were
pleased that the nickel-catalyzed homo-coupling conditions
reported by Lin8 and coworker were applicable and led to the
formation of homocoupling product 3a in 68% yield. Installations
of alkyl substituents were easily accomplished by treatment of 3a
under conditions of LDA/RI to form 3b-e in acceptable yields.
Finally, stereospecific reduction of bisphosphine oxides 3a-e under
conditions of HSiCl3/Et3N formed ligands L1-5 in good yields.
With ligands L1-5 in hand, we studied palladium-catalyzed
asymmetric hydrogenation9 of ethyl 3-oxo-3-phenylpropanoate
(4a). The reactions were initially performed at rt under 450 psi H2
pressure with trifluoroethanol as the solvent in the presence of
Pd(OCOCF3)2 (2 mol %) and chiral ligand (2.2 mol %). As shown in
Table 1, all ligands L1-5 provided full converstions but with
dramatically different enantioselectivities (entries 1-5). While
The development of chiral phosphorus ligands with novel
structural motif have played a significant role for the development
of new efficient transition-metal-catalyzed asymmetric reactions.4
Although atropisomeric biaryl bisphosphine ligands such as BINAP,
BIPHEP and related ligands have demonstrated high efficiencies in
a number of asymmetric catalytic reactions, their limitations in
controlling enantioselectivity and reactivity are observed on many
occasions.1f,5 It is therefore important to design biaryl
bisphosphorus ligands with new structural motif. Efficient P-chiral
biaryl bisphosphorus ligands are rarely reported.6 Herein we report
the development of new and tunable P-chiral bisphosphorus
ligands L1-5 (BABIBOPs) that possess the following features: a) The
chiral elements of the ligands are largely originated from the
central P-chirality instead of the biaryl axial chirality; b) The biaryl
chelating ligands adopt the coordination modes with transition
metals similar to BINAP- or BIPHEP-type ligands; c) Such ligands
containing dihydrobenzooxophosphole framework7 provide well-
defined yet tunable chiral environment. Modification of its steric
properties can be accomplished by simple variations of the R
groups at 2,2’ positions. Applications of these ligands L1-5 in
palladium-catalyzed asymmetric hydrogenation of β-aryl-β-keto
esters are studied. Excellent enantioselectivities (up to >99% ee)
and turnover numbers (up to 10,000) have been achieved on these
substrates for the first time with a chiral palladium catalyst.
This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which
may lead to differences between this version and the Version of Record. Please cite this
article as doi: 10.1002/cjoc.201700645
This article is protected by copyright. All rights reserved.

Scheme 1 Syntheses of Ligands L1-5
8
9
L3
L3
L3
L3
THF
<5
N/A
(CF3)2CHOH
CF3CF2CH2OH
CF3CF2CH2OH
100
100
100
89 (R)
95 (R)
98 (R)
10
11d
a
Unless otherwise stated, the reactions were performed in designated
solvent under 450 psi H2 at rt for 12 h with 4a (0.25 mmol), Pd(OCOCF3)2 (2
mol %), and ligand (2.2 mol %). b Determined by GC. c Determined by chiral
HPLC on
a Chiralcel OD-H column. The absolute configuration was
determined by comparing its optical rotation with reported data.10a d T = 0
oC.
The substrate scope of the palladium-catalyzed asymmetric
hydrogenation of β-aryl substituted β-keto esters with the Pd-L3
catalyst was explored. As can be seen from Table 2, the substrates
were not limited to ethyl esters, the methyl and tert-butyl esters 5b
and 5c were also formed in excellent yields and ees (entries 1-2). A
series of substituted β-aryl-β-keto ethyl esters with different
electronic properties and substitution patterns were further
hydrogenated and the corresponding β-hydroxy carboxylic esters
were obtained in excellent yields and enantioselectivities (entries 3-
13). Both electron-rich and electron-deficient substrates were well
tolerable (entries 3,5). para-, meta-, and ortho-Substituted β-aryl-β-
keto esters were all hydrogenated smoothly to form hydrogenation
products in excellent ees (entries 3-13). Besides β-aryl-β-keto
esters, β-alkyl-β-keto esters (4o-q) were also suitable substrates to
provide corresponding alcohols (5o-q) in high ees (entries 14-16).
Experimental details: a) NH2Boc (2.0 equiv), CsF (1.4 equiv), Xantphos
(10 mol %), Pd2(dba)3 (5 mol %), THF, 75 oC, 50%; b) CF3COOH (14 equiv),
DCM, 0 oC to rt, 90%; c) NaNO2 (2.0 equiv), HCl (15 equiv), KI (4.0 equiv),
CH3CN/H2O = 8/3 (v/v), -20 oC to rt, 73%; d) NiCl2(PPh3)2 (0.25 equiv), PPh3
(0.5 equiv), Zn (3.0 equiv), NaH (8.0 equiv), THF, 80 oC, 68%; e) LDA (5.0
equiv), RI (5.0 equiv), THF, -78 oC to rt, 50% (3b), 85% (3c), 49% (3d), 37%
(3e); f) HSiCl3 (15 equiv), TEA (20 equiv), toluene, 110oC, 95% (L1), 93% (L2),
95% (L3), 93% (L4), 93% (L5).
Table 2 Palladium-catalyzed asymmetric hydrogenation of ethyl 3-oxo-3-
phenylpropanoate
ligands L2-5 consistently led to one enantiomer preferentially,
ligand L1 provided the major reduction product with the opposite
configuration. This observation indicated the influence of the steric
properties at the vicinity of the phosphorus centers on
enantioselectivity and stereo-configuration, and further
demonstrated the importance of ligand modularity in developing
efficient asymmetric catalytic reactions. Among these five ligands,
iPr-BABIBOP (L3) provided a best ee (93%, entry 3). Study of the
solvent effect with the Pd-iPr-BABIBOP catalyst disclosed that
solvent played a significant role for the high reactivity (entries 6-
10). While trifluoroethanol provided a complete conversion, MeOH,
EtOH, and THF did not lead to the reduction product. Further
screening of various fluorine-containing alcohols showed that
pentafluoropropanol was beneficial for the enantioselectivity,
providing 5a in 95% ee (entry 10). Interestingly, the hydrogenation
proceeded even at 0 oC to form chiral alcohol 5a in 98% ee (entry
11). It should be noted that this was the highest enantioselectivity
reported in asymmetric hydrogenation of β-aryl-β-keto esters with
a chiral palladium catalyst.
Entriesa
R,R’
Yield (%)b
99
Ee (%)c
98(5b)
>99(5c)
>99(5d)
>99(5e)
98(5f)
1
2
C6H5,Me (4b)
C6H5,tBu (4c)
99
3
p-MeOC6H4,Et (4d)
p-MeC6H4,Et (4e)
p-FC6H4,Et (4f)
p-ClC6H4,Et (4g)
p-BrC6H4,Et (4h)
p-IC6H4,Et (4i)
p-CF3C6H4,Et (4j)
m-MeC6H4,Et (4k)
m-MeOC6H4,Et (4l)
o-MeOC6H4,Et (4m)
o-MeC6H4,Et (4n)
Me,Et (4o)
99
4
99
5
99
6
99
97(5g)
97(5h)
97(5i)
7
99
8
99
9
99
97(5j)
Table 1 Palladium-catalyzed asymmetric hydrogenation of ethyl 3-oxo-3-
phenylpropanoate
10
11
12
13
14
15
16
99
99(5k)
98(5l)
99
99
>99(5m)
93(5n)
98(5o)
95(5p)
92(5q)
99
99
Et,Et (4p)
99
Entriesa
Ligandb
L1
Solvent
TFE
conv (%)b
100
100
100
100
100
<5
Ee (%)c
66 (S)
81 (R)
93 (R)
89 (R)
42 (R)
N/A
iPr,Et (4q)
99
1
2
3
4
5
6
7
a Unless otherwise stated, the reactions were performed in CF3CF2CH2OH
under 450 psi H2 at 0 oC for 12 h with 4b-k (0.25 mmol), Pd(OCOCF3)2 (2
mol %), and L3 (2.2 mol %). b Isolated yields. c Determined by chiral HPLC on
OD-H, AD-H, OJ-H or ID-3 column. The absolute configuration was
determined by comparing its optical rotation with reported data.10a-10h
L2
TFE
L3
TFE
L4
TFE
L5
TFE
Besides β-aryl substituted β-keto esters, other functionalized
ketones such as α-phthalimide ketone, α-benzoylamino ketone, α-
benzoyloxy ketone, and α-keto ester were also suitable substrates
L3
MeOH
EtOH
L3
<5
N/A
This article is protected by copyright. All rights reserved.

to provide corresponding alcohols 6-9 in good to excellent ees with
a Pd-L1 or Pd-L3 catalyst (Figure 2).
OH
O
P
P
H
O
OEt
O
Pd
B
CF3
H+
A
H
O
CF3COO
P
P
O+
P
H
O
Pd
OEt
L3
≡
O
P
H
Figure 2 Asymmetric hydrogenation of other ketones with the Pd-L1 or Pd-
L3 catalyst
CF3
O
P
P
H
O
E
Pd
CF3
C
OH
O
H
OEt
O
H
O
5a
OEt
H
H2
O
P
P
Pd+
O
CF3
D
Figure 4 A proposed mechanism
Conclusions
In summary, we have developed a series of structurally novel
P-chiral biaryl bisphosphorus ligands BABIBOPs that have shown
high efficiency in palladium-catalyzed asymmetric hydrogenation.
With the Pd-iPr-BABIBOP catalyst, excellent enantioselectivities
(up to >99% ee) and turnover numbers (10,000 TON) have been
achieved for the first time in Pd-catalyzed asymmetric
hydrogenation of β-aryl or β-alkyl substituted β-keto esters,
providing an efficient method for the syntheses of a series of
functionalized chiral alcohols. The high tunability of these ligands
holds promise to be applicable to a variety of asymmetric catalytic
reactions and research in this direction is actively ongoing in our
laboratory.
Figure 3 The X-ray structure of Pd(L1)(OCOCF3)2 [the H atoms and
chloroform are omitted for clarity, selected bond lengths (Å): 2.212, 2.218
(Pd−P), selected bond angle (o): 92.4 (P −Pd− P)]
Supporting Information
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2018xxxxx.
Acknowledgement
The work is supported by the Strategic Priority Research
Program of the Chinese Academy of Sciences XDB20000000, CAS
(QYZDY-SSW-SLH029), NSFC-21432007, 21572246, and K.C.Wong
Education Foundation.
Scheme 2 Gram-scale hydrogenation of 4a with the Pd-L3 catalyst
To demonstrate the practicality of this hydrogenation
methodology, both palladium complexes Pd(L1)(OCOCF3)2 and
Pd(L3)(OCOCF3)2 were prepared. The X-ray structure11 of the
Pd(L1)(OCOCF3)2 complex (Figure 3) revealed a nearly square
planer geometry of the palladium center coordinated with the C2-
symmetrical BABIBOP(L1) and two trifluoroacetates. By employing
Pd(L3)(OCOCF3)2 (0.01 mol %) as the catalyst precursor,
hydrogenation of 4a (2.39 g) proceeded smoothly in
pentafluoropropanol (2 mL) and TFA (0.7 mL) under 30 atm of
hydrogenation pressure for 2 days, providing 5a in 93% ee and 99%
yield (Scheme 2). It should be noted this is the highest turnover
number (10,000) reported to date to our knowledge.
References
[1] For recent reviews in asymmetric hydrogenation, see: (a) Zhang, Z.;
Butt, N. A.; Zhang, W. Chem. Rev. 2016, 116, 14769. (b) Verendel, J. J.;
Pàmies, O.; Diéguez, M.; Andersson, P. G. Chem. Rev. 2014, 114, 2130.
(c) Wang, D.-S.; Chen, Q.-A.; Lu, S.-M.; Zhou, Y.-G. Chem. Rev. 2012, 112,
2557. (d) Opalaiah, K.; Kagan, H. B. Chem. Rev. 2011, 111, 4599. (e) Xie,
J.-H.; Zhu, S.-F.; Zhou, Q.-L. Chem. Rev. 2011, 111, 1713. (f) Tang, W.;
Zhang, X. Chem. Rev. 2003, 103, 3029. (g) Asymmetric Catalysis on
Industrial Scale: Challenges, Approaches and Solutions; Blaser, H.-U.;
Schmidt, E. Eds.; Wiley-VCH: Weinheim, 2004. (h) Comprehensive
Asymmetric Catalysis; Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H., Eds.;
Springer: Berlin, 1999.
[2] For a recent review on palladium-catalyzed asymmetric hydrogenation,
see: Chen, Q.-A.; Ye, Z.-S.; Duan, Y.; Zhou, Y.-G. Chem. Soc. Rev. 2013,
42, 497.
[3] For selected reports on palladium-catalyzed asymmetric hydrogenation:
(a) Chen, Z.-P.; Hu, S.-B; Chen, M.-W.; Zhou, Y.-G. Org. Lett. 2016, 18,
On the basis of Fan and Zhou’s mechanistic work3e and our
own investigations, we proposed a mechanism of the palladium-
catalyzed asymmetric hydrogenation of β-aryl substituted β-keto
esters illustrated in Figure 4. The palladium hydride species A
interacts with the protonated substrate B under acidic conditions
to form complex C, which undgoes hydride tranfer to provide the
cationic palladium species D. Disocciation of the reduction product
5a followed by coordination of hydrogen forms complex E, which
eliminates a proton to regenerate the palladium hydride species A.
This article is protected by copyright. All rights reserved.

2676. (b) Song, B.; Yu, C.-B.; Huang, W.-X.; Chen, M.-W.; Zhou, Y.-G.
Org. Lett. 2015, 17, 190. (c) Chen, Z.-P.; Chen, M.-W.; Shi, L.; Yu, C.-B.;
Zhou, Y.-G. Chem. Sci. 2015, 6, 3415. (d) Cai, X.-F.; Huang, W.-X.; Chen,
Z.-P.; Zhou, Y.-G. Chem. Commun., 2014, 50, 9588. (e) Duan, Y.; Li, L.;
Chen, M.-W.; Yu, C.-B.; Fan, H.-J.; Zhou, Y.-G. J. Am. Chem. Soc. 2014,
136, 7688. (f) Yu, C.-B.; Huang, W.-X.; Shi, L.; Chen, M.-W.; Wu, B.; Zhou,
Y.-G. J. Am. Chem. Soc. 2014, 136, 15837. (g) Li, C.; Chen, J.; Fu, G.; Liu,
D.; Liu, Y.; Zhang, W. Tetrahedron 2013, 69, 6839. (h) Chen, J.; Liu, D.;
Butt, N.; Li, C.; Fan, D.; Liu, Y.; Zhang, W. Angew. Chem. Int. Ed. 2013,
52, 11632. (i) Wang, C.; Yang, G.; Zhuang, J.; Zhang, W. Tetrahedron
Lett. 2010, 51, 2044. (j) Yang, Q.; Shang, G.; Gao, W.; Deng, J.; Zhang X.
Angew. Chem. Int. Ed. 2006, 45, 3832. (k) Wang, C.-Q.; Lu, S.-M.; Zhou,
Y.-G. Org. Lett., 2005, 7, 3235. (l) Wang, D.-S.; Chen, Q.-A.; Li, W.; Yu,
C.-B.; Zhou, Y.-G.; Zhang, X. J. Am. Chem. Soc. 2010, 132, 8909. (m)
Wang, D.-S.; Ye, Z.-S.; Chen, Q.-A.; Zhou, Y.-G.; Yu, C.-B.; Fan, H.-J.,
Duan, Y. J. Am. Chem. Soc. 2011, 133, 8866. (n) Wang, Z.; Zhang, Z.; Liu,
Y.; Zhang, W. Chin. J. Org. Chem. 2016, 36, 274. (o) Yuan, Q.; Zhang,
W. Chin. J. Org. Chem. 2016, 36, 447.
Chem. Soc. 2014, 136, 570. (i) Li, C.; Chen, D.; Tang, W. Synlett 2016,
27, 2183.
[8] Liu, G.-Q., Hong, R. J. Org. Chem. 2001, 66, 2877.
[9] For representative examples of asymmetric hydrogenation of ethyl 3-
oxo-3-phenylpropanoate with other transition metal catalysts, see: (a)
Li, Y.; Yu, S.; Wu, X.; Xiao, J.; Shen, W.; Dong, Z.; Gao, J. J. Am. Chem.
Soc. 2014, 136, 4031. (b) Xie, J.; Liu, X.; Yang, X.; Xie, J.; Wang, L.; Zhou,
Q. Angew. Chem. Int. Ed. 2012, 51, 201. (c) Qiu, L.; Kwong, F.; Wu, J.;
Lam, W.; Chan, S.; Yu, W.; Li, Y.; Guo, R.; Zhou, Z.; Chan, A. J. Am. Chem.
Soc. 2006, 128, 5955. (d) Jeulin, S.; Duprat de Paule, S.;
Ratovelomanana-Vidal, V.; Genet, J.; Champion, N.; Dellis, P. Angew.
Chem. Int. Ed. 2004, 43, 320. (e) Hu, A.; Ngo, H.; Lin, W. Angew. Chem.
Int. Ed. 2004, 43, 2501. (f) Junge, K.; Dipl, B.; Enthaler, S.; Oehme, G.;
Michalik, M.; Monsees, A.; Riermeier, T.; Dingerdissen, U.; Beller, M.
Angew. Chem. Int. Ed. 2004, 43, 5066. (g) Hu, A.; Ngo, H. L.; Lin, W.
Angew. Chem. Int. Ed. 2003, 42, 6000. (h) Lotz, M.; Polborn, K.;
Knochel, P. Angew. Chem. Int. Ed. 2002, 41, 4708. (i) Zhou, Y.-G.; Tang,
W.; Wang, W.-B.; Li, W.; Zhang, X. J. Am. Chem. Soc. 2002, 124, 4952.
(j) Ireland, T.; Grossheimann, G.; Wieser-Jeunesse, C.; Knochel, P.
Angew. Chem. Int. Ed. 1999, 38, 3212. (k) Noyori, R.; Ohkuma, T.;
Kitamura, M.; Takaya, H.; Sayo, N.; Kumobayashi, H.; Akutagawa, S. J.
Am. Chem. Soc. 1987, 109, 5856.
[10] (a) Xie, J.; Liu, X.; Yang, X.; Xie, J.; Wang, L.; Zhou, Q. Angew. Chem. Int.
Ed. 2012, 51, 201. (b) Padhi, S. K.; Titu, D.; Pandian, N. G.; Chadha, A.
Tetrahedron. 2006, 62, 5133. (c) Shiomi, T.; Adachi, T.; Toribatake, K.;
Zhou, L.; Nishiyama, H. Chem. Commun. 2009, 40, 5987. (d) Xu, C.;
Yuan, C. Tetrahedron. 2005, 61, 2169. (e) Ariger, M. A.; Carreira, E. M.
Org. Lett. 2012, 14, 4522. (f) Niu, Z.; Chen, J.; Chen, Z., Ma, M.; Song,
C.;Ma, Y. J. Org. Chem. 2015, 80, 602. (g) Carnell, A. J.; Head, R.;
Schneider, M. Tetrahedron: Asymmetry. 2004, 15, 821. (h) Ji-Eon, L.;
Jaesook, Y. Angew. Chem. Int. Ed. 2008, 47, 145.
[4] Fu, W.; Tang, W. ACS Catal. 2016, 6, 4814.
[5] (a) Berthod, M.; Mignani, G.; Woodward, G.; Lemaire, M. Chem. Rev.
2005, 105, 1801. (b) Noyori, R. Adv. Synth. Catal. 2003, 345, 15.
[6] (a) Dutartre, M.; Bayardon, J.; Jugé, S. Chem. Soc. Rev. 2016, 45, 5771.
(b) Juge, S.; Bayardon, J.; Remond, E.; Laureano, H.; Henry, J.-C.;
Leroux, F.; Colobert, F. US 20140142325.
[7] (a) Tang, W.; Qu, B.; Capacci, A. G.; Rodriguez, S.; Wei, X.; Haddad, N.;
Narayanan, B.; Ma, S.; Grinberg, N.; Yee, N. K.; Krishnamurthy, S.;
Senanayake, C. H. Org. Lett. 2010, 12, 176. (b) Li, W.; Rodriguez, S.;
Duran, A.; Sun, X.; Tang, W.; Premasiri, A.; Wang, J.; Sidhu, K.; Patel, N.
D.; Savoie, J.; Qu, B.; Lee, H.; Haddad, N.; Lorenz, J. C.; Nummy, L.;
Hossain, A.; Yee, N.; Senanayake, C. H. Org. Process Res. Dev. 2013, 17,
1061. (c) Liu, G.; Liu, X.; Cai, Z.; Jiao, G.; Xu, G.; Tang, W. Angew. Chem.
Int. Ed. 2013, 52, 4235. (d) Huang, L.; Zhu, J.; Jiao, G.; Wang, Z.; Yu, X.;
Deng, W.-P.; Tang, W. Angew. Chem. Int. Ed. 2016, 55, 4527. (e) Tang,
W.; Capacci, A. G.; Wei, X.; Li, W.; White, A.; Patel, N. D.; Savoie, J.; Gao,
J. J.; Rodriguez, S.; Qu, B.; Haddad, N.; Lu, B. Z.; Krishnamurthy, D.; Yee,
N. K.; Senanayake, C. H. Angew. Chem. Int. Ed. 2010, 49, 5879. (f) Zhao,
Q.; Li, C.; Senanayanke, C. H.; Tang, W. Chem. Eur. J. 2013, 19, 2261. (g)
Tang, W.; Patel, N. D.; Xu, G.; Xu, X.; Savoie, J.; Ma, S.; Hao, M.-H.;
Keshipeddy, S.; Capacci, A. G.; Wei, X.; Zhang, Y.; Gao, J. J.; Li, W.;
Rodriguez, S.; Lu, B. Z.; Yee, N. K.; Senanayake, C. H. Org. Lett. 2012, 14,
2258. (h) Xu, G.; Fu, W.; Liu, G.; Senanayanke, C. H.; Tang, W. J. Am.
[11] The CIF for the crystal structure of Pd(L1)(OCOCF3)2 has been deposited
with the CCDC and has been given the deposition number CCDC
1586545.
Manuscript received: XXXX, 2017
Revised manuscript received: XXXX, 2017
Accepted manuscript online: XXXX, 2017
Version of record online: XXXX, 2017
This article is protected by copyright. All rights reserved.

Entry for the Table of Contents
Chin. J. Chem. 2018,
Efficient P-Chiral Biaryl Bisphosphorus
Ligands
for
Palladium-Catalyzed
Asymmetric Hydrogenation
A series of structurally novel P-chiral biaryl bisphosphorus ligands BABIBOPs are
developed, providing high ees and TONs for the first time in palladium-catalyzed
asymmetric hydrogenation of β-aryl and β-alkyl substituted β-keto esters.
Wenhao Jiang, Qing Zhao, Wenjun
Tang*
This article is protected by copyright. All rights reserved.