Axial 4,4′,6,6′-tetrakis-trifluoromethyl-biphenyl-2, 2′diamine (TF-BIPHAM): Resolution and applications in asymmetric hydrogenation

Article abstract of DOI:10.1021/ol8018677

(Equation Presented) The racemic TF-BIPHAM was resolved for the first time, and the effectiveness of the resolved diamine was demonstrated by highly enantioselective hydrogenation of α-aryl enamides and α-dehydroamino acid esters using readily accessible

Full text of DOI:10.1021/ol8018677

ORGANIC
LETTERS
2008
Vol. 10, No. 21
4711-4714
Axial 4,4′,6,6′-Tetrakis-trifluoromethyl-
biphenyl-2,2′-diamine (TF-BIPHAM):
Resolution and Applications in
Asymmetric Hydrogenation
Chun-Jiang Wang,* Feng Gao, and Gang Liang
College of Chemistry and Molecular Sciences, Wuhan UniVersity, 430072, China
cjwang@whu.edu.cn
Received July 8, 2008
ABSTRACT
The racemic TF-BIPHAM was resolved for the first time, and the effectiveness of the resolved diamine was demonstrated by highly enantioselective
hydrogenation of r-aryl enamides and r-dehydroamino acid esters using readily accessible bis(aminophosphine) ligands.
Catalytic asymmetric reaction is one of the most powerful
methods for the synthesis of enantiomerically enriched
products, and ligand design based on a chiral backbone plays
a crucial role in this area.1 Among various applied chiral
skeletons, atropisomeric biaryl backbones, most notably 1,1′-
binaphthalene derivatives (e.g., BINOL, BINAP and BI-
NAM), occupy an important position in asymmetric synthesis
(Figure 1).2 Inspired by the tremendous success of BINAP
in asymmetric catalysis,3 some C2-symmetric biphenyl
diphosphines such as MeO-BIPHEP,4 TunePhos,5 SEGPhos,6
and P-Phos7 have been documented as efficient ligands in
asymmetric hydrogenation. Compared to the binaphthalene
counterpart, the steric and electronic properties of the
atropisomeric biphenyl framework are more easily modified.8
We are interested in the development of a new type of C2-
symmetric biphenyldiamine: the 4,4′,6,6′-Tetrakis-trifluoro-
methyl-biphenyl-2,2′-diamine (abbreviated to TF-BIPHAM).
Its precursor, dinitro compound, was reported early in 1949,9
however, the racemic TF-BIPHAM was first utilized as an
important intermediate for the synthesis of one less efficient
chiral ligand BIFUP until 1991.10 To the best of our
(1) (a) Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-
VCH: Weinheim, 2000. (b) ComprehensiVe Asymmetric Catalysi I-III;
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999.
(c) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley: New
York, 1994.
(2) For recent reviews, see: (a) Chen, Y.; Yekta, S.; Yudin, A. K. Chem.
ReV. 2003, 103, 3155. (b) Brunel, J. M. Chem. ReV. 2005, 105, 857. and
2007, 107, PR1. (c) Berthod, M.; Mignani, G.; Woodward, G.; Lemaire,
M. Chem. ReV. 2005, 105, 1801. (d) Telfer, S. G.; Kuroda, R. Coord. Chem.
ReV. 2003, 242, 33.
(5) Zhang, Z.; Qian, H.; Longmire, J.; Zhang, X. J. Org. Chem. 2000,
65, 6223.
(6) Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura,
T.; Kumobayashi, H. AdV. Synth. Catal. 2001, 343, 264.
(7) Pai, C.-C.; Lin, C.-W.; Lin, C.-C.; Chen, C.-C.; Chan, A. S. C.;
Wong, W. T. J. Am. Chem. Soc. 2000, 122, 11513.
(3) (a) Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.;
Souchi, T.; Noyori, R. J. Am. Chem. Soc. 1980, 102, 7932. (b) Noyori, R.
Angew. Chem., Int. Ed. 2002, 41, 2008.
(4) Schmid, R.; Broger, E. A.; Cereghtti, M.; Crameri, Y.; Foricher, J.;
Lalonde, M.; Muller, R. K.; Scalone, M.; Schoettel, G.; Zutter, U. Pure
Appl. Chem. 1996, 68, 131.
(8) For reviews: (a) McCarthy, M.; Guiry, P. J. Tetrahedron 2001, 57,
3809. (b) Shimizu, H.; Nagasaki, I.; Saito, T. Tetrahedron 2005, 61, 5405.
(9) Bradsher, C. K.; Bond, J. B. J. Am. Chem. Soc. 1949, 71, 2659.
10.1021/ol8018677 CCC: $40.75
Published on Web 09/26/2008
2008 American Chemical Society

Scheme 1. Resolution of TF-BIPHAM
Figure 1
BIPHAM.
. Some atropisomeric chiral biaryl ligands and TF-
knowledge, the resolution and applications of this potential
chiral backbone in asymmetric catalysis have not been
reported so far.
Herein, we report the first resolution of racemic TF-
BIPHAM, and the development of a class of efficient
bis(aminophosphine) ligands using the resolved diamine.
These bis(aminophosphine) ligands exhibit excellent to
almost perfect enantioselectivity in Rh-catalyzed asymmetric
hydrogenation of enamides and R-dehydroamino acid es-
ters.11
under mild condition furnished each enantiomer in high
overall yield. The enantiomeric excess, determined by chiral
HPLC (Chiralpak AS-H column, hexane/isopropanol 95:5,
1 mL/min), was found to be >99.9% ee in each case. The
(S)-configuration of the (-)-enantiomer was determined by
the X-ray analysis of the corresponding diastereomer (S,S)-2
(Figure 2).15,16
The preparation of racemic TF-BIPHAM was carried out
by following the reported method in >80% yield from the
commercially available 2,4-bis(trifluoromethyl)-bromoben-
zene in 3 steps.10,12 After several unsuccessful attempts to
resolve the racemic TF-BIPHAM through inclusion crystal-
lization,13 we were able to obtain the two optical diamines
through highly efficient chromatography resolution of the
corresponding diastereomeric disulfonamide derived from
inexpensive (1S)-camphor-10-sulfonyl chloride and then
hydrolyzation of each pure diastereomer with sulfuric acid
(Scheme 1).14 The two disulfonamides of (()-TF-BIPHAM
showed unusually large separation factors on TLC plates,
which allowed their separation by simple column chroma-
tography. Removal of the (1S)-camphor-10-sulfonyl moieties
Figure 2. X-ray Crystal Structure of (S,S)-2.
(10) Murata, M.; Morimoto, T.; Achiwa, K. Synlett. 1991, 827.
(11) For recent reviews, see: (a) Tang, W.; Zhang, X. Chem. ReV. 2003,
103, 3029. (b) Zhang, W.; Chi, Y.; Zhang, X. Acc. Chem. Res. 2007, 40,
1278.
With enantiopure 1 in hand, we extended its application
to the synthesis of a new type of C2-symmetric bis(amino-
phosphine) ligands 3. As shown in Scheme 2, the chiral
ligands 3 were conveniently obtained in good yields by
lithiation of (S)-1 with n-BuLi and then reaction with R2PCl.
Ligands 3 are stable enough to be purified by column
chromatography in air. The enhanced stability of the ligands
could be possibly attributed to the four strong electron-
withdrawing trifluoromethyl groups attached to the biphenyl
backbone.
(12) 2,4-bis(trifluoromethyl)-bromobenzene can be synthesized from
much cheaper compound 1,3-bis(trifluoromethyl)benezen directely, See:
Leconte, S.; Ruzziconi, R. J. Fluorine Chem. 2002, 117, 167
.
(13) (a) Inclusion Compounds; Atwood, J. L., Davies, J. E. D., MacNicol,
D. D., Eds.; Academic Press: London, 1984; Vols. I-III; Oxford University
Press: Oxford, 1991; Vols. IV, V. (b) Molecular Inclusion and Molecular
Recognition-Clathrates I and II; Weber, E., Ed.; Topics in Current
Chemistry; Springer: Berlin, 1987, 1988; Vols. 140, 149. (c) Tanaka, K.;
Okada, T.; Toda, F. Angew. Chem., Int. Ed. Engl. 1993, 32, 1147. (d) Toda,
F.; Tanaka, K.; Stein, Z.; Goldberg, I. J. Org. Chem. 1994, 59, 5748. (e)
Toda, F.; Tanaka, K. Chem. Commun. 1997, 1087. (f) Ding, K.; Wang, Y.;
Yun, H.; Liu, J.; Wu, Y.; Terada, M.; Okubo, Y.; Mikami, K. Chem.-Eur.
J. 1999, 5, 1734. (g) Periasamy, M.; Venkatraman, L.; Thomas, K. R. J. J.
Org. Chem. 1997, 62, 4302.
The catalytic performance of ligands 3 were initially tested
in the Rh(I)-catalyzed hydrogenation of aryl enamide sub-
(14) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic
Synthesis, 3rd ed.; John Wiley & Sons, Inc.: New York, 1999.
4712
Org. Lett., Vol. 10, No. 21, 2008

Encouraged by these results, we then applied ligands 3a
and 3b in the Rh(I)-catalyzed hydrogenation of other R-aryl
enamides under the optimized conditions (Table 2). It appears
Scheme 2
.
Synthesis of the C2-Symmetric Bis(aminophosphine)s
from the Resolved TF-BIPHAM
Table 2. Rh-Catalyzed Asymmetric Hydrogenation of Enamides
4a
entry
substrate
Ar
ee (%)b,c
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4a
Ph
99.5 (99.2)
99.4 (99.3)
99.7 (99.1)
99.2 (99.3)
98.2 (97.8)
99.8 (99.2)
99.9 (99.6)
99.6 (99.4)
99.5 (99.0)
97.6 (95.5)
99.2 (99.0)
99.0 (99.3)
99.3 (99.0)
99.0
m-Me-Ph
p-Me-Ph
m-Cl-Ph
p-Cl-Ph
m-Br-Ph
p-Br-Ph
m-MeO-Ph
p-MeO-Ph
o-F-Ph
strate 4a.11 As shown in Table 1, the catalytic activity of
Table 1. Screening Studies of Asymmetric Hydrogenation of
Enamide 4aa
9
10
11
12
13
14
p-F-Ph
p-CF3-Ph
2-naphtyl
Ph
entryb ligand
solvent
temp (°C) PH2 (atm) ee (%)c,d
1
3a
3a
3a
3b
3c
3d
3a
3b
3a
3a
3a
3a
3a
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
Acetone
EtOAc
DCM
rt
rt
rt
rt
rt
rt
5
5
5
5
5
10
3
97.4
97.0
97.5
97.9
10.7
5.8
99.2
99.5
98.7
99.1
97.3
97.0
97.5
a In all cases, full conversion was achieved. b Enantiomeric excesses
were determined by GC or HPLC. The absolute configuration of the products
was determined by comparing the retention times with the reported data in
the literature. c Data in parentheses was achieved by using 3a as the chiral
ligand. d S/C ) 1000.
2e
3f
4
50
10
10
10
10
10
10
10
10
10
10
5
6
7
8
that the position and the electronic property of the substit-
uents on the aromatic rings had a very limited effect on the
enantioselectivities. In all cases, ligands 3a and 3b exhibited
similar excellent enantioselectivities. Further optimization
showed that high yield and enantioselectivity remained when
the reaction was performed with as low as 0.1 mol% of
catalyst loading. (Table 2, entry 14).
9
10
11
12
13
MeOH
THF
5
5
a Unless otherwise noted, the reactions were carried out with a S/C )
200:1. b In all cases, full conversion was achieved. c Enantiomeric excesses
were determined by GC using a Chiral Select 1000 capillary column.
d Absolute configuration of the products was determined by comparing the
GC retention times with the reported data in the literature. e Reaction time
) 10 h. f Reaction time ) 20 min.
Remarkable enantioselectivity and catalytic activity were
also observed in the Rh(I)-catalyzed asymmetric hydrogena-
tion of R-dehydroamino acid esters with ligand 3b.11 As
shown in Table 3, a wide array of substituted phenylalanine
derivatives were formed with excellent enantioselectivities
regardless of the position and the electronic property of the
substituents on the phenyl ring (Table 3, entries 2, 4-12).
Hydrogenation of 6a and 6k with the reduced catalyst loading
(0.1-0.02 mol%) still afforded the corresponding products
in full conversion with 99% ee. (Table 3, entries 3 and 14).
ligands 3a and 3b was found to be superior to that of ligands
3c and 3d (Table 1, entries 1 and 4-6). These results
demonstrated the importance of the steric and electronic
effects of the ligands on the enantioselectivities: when the
phenyl group on the phosphorus atom of ligand 3a was
replaced by more steric hindered but electron-withdrawing
3,5-bis(trifluoromethyl)phenyl group, the enantioselectivity
decreased significantly; ligand 3d containing cyclohexyl
group on the phosphorus atom, displayed a similarly negative
effect on the enantioselectivity. The hydrogen pressure has
influence only on the reaction rate not on the enantioselec-
tivity (Table 1, entries 1-3). A preliminary screening of
solvent effects showed that there was no significant difference
among the tested solvents (Table 1, entries 7-13). Reducing
the temperature to 5 °C in toluene led to complete reaction
with >99% ee within 30 min (Table 1, entries 7 and 8).
(15) Crystal data for (S,S)-2: C36H36F12N2O6S2, Mr ) 884.79, T ) 150
K, Orthorhombic, space group P212121, a ) 13.8439(5), b ) 14.6436(6),
c ) 37.6480(14) Å, V ) 7632.2(5) Å3, Z ) 8, 13 657 unique reflections,
final R1 ) 0.0886 and wR2 ) 0.1961 for 11 145 observed [I > 2σ(I)]
reflections. Higher parameters R1 and wR2 may be ascribed to the poor
data quality. CCDC 692522 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystal-
lographic Data Centre, 12, Union Road, Cambridge CB21EZ, UK; fax:
(+44) 1223-336-033; or deposit@ccdc.cam.ac.uk).
(16) (a) Flack, H. D. Acta Crystallogr. 1983, A39, 876. (b) Flack, H. D.;
Bernardinelli, G. Acta Crystallogr. 1999, A55, 908.
Org. Lett., Vol. 10, No. 21, 2008
4713

In conclusion, the chiral TF-BIPHAM was resolved
through a rapid and reliable procedure for the first time,
which diversifies the family of chiral biphenyl backbones.
The effectiveness of TF-BIPHAM was demonstrated by
highly enantioselective hydrogenation of R-aryl enamides and
R-dehydroamino acid esters using readily accessible bis(ami-
nophosphine) ligands. Further application of the resolved
chiral diamine in asymmetric catalysis is ongoing in our
laboratory and will be reported in due course.
Table 3. Rh-Catalyzed Asymmetric Hydrogenation of
(Z)-Acetamido-3-arylacrylic Acid Methyl Estersa
entry
substrate
R
ligand
ee (%)b
1
6a
6a
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
Ph
Ph
Ph
3a
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
97.4
99.0
99.1
99.0
99.0
98.7
98.6
98.1
99.0
98.5
98.0
98.5
99.8
99.9
2
3c
4
Acknowledgment. This work was supported by National
Natural Science Foundation of China (20642005, 20702039)
and the startup fund from Wuhan University. We thank Mr.
Wei Li at Penn State University and Dr. Malati Raghunath
at Veterinary Medicine Pharmaceutical Sciences, Pfizer
Animal Health (India) for English review and Prof. Yuepeng
Cai in South China Normal University for solving the crystal
structure. Dedicated to Professor Xiyan Lu on the occasion
of his 80th birthday.
o-Me-Ph
p-Me-Ph
o-Cl-Ph
m-Cl-Ph
p-Cl-Ph
o-MeO-Ph
m-MeO-Ph
p-MeO-Ph
p-F-Ph
H
5
6
7
8
9
10
11
12
13
14
6k
H
Supporting Information Available: Experimental pro-
cedures and compound characterization data. This material
is available free of charge via the Internet at http://pubs.acs.org.
a In all cases, full conversion was achieved. b Enantiomeric excesses
were determined by GC or HPLC. The absolute configuration of the products
was determined by comparing the retention times with the reported data in
the literature. c S/C ) 1000, 12 h. d S/C ) 5000, 12 h.
OL8018677
In comparison with the literature results achieved by similar
bis(aminophosphine) ligands such as BDPAB,17
H8-BDPAB18 derived from chiral 1,1′-binaphthyl-2,2′-
diamine (BINAM), and MABP derived from chiral 6,6′-
dimethyl-biphenyl-2,2′-diamine,19 our catalyst system shows
comparable reactivities but higher enantioselectivities.
(17) (a) Miyano, S.; Nawa, M.; Hashimoto, H. Chem. Lett. 1980, 729.
(b) Miyano, S.; Nawa, M.; Mori, A.; Hashimoto, H. Bull. Chem. Soc. Jpn.
1984, 57, 2171.
(18) (a) Zhang, F.-Y.; Pai, C.-C.; Chan, A. S. C. J. Am. Chem. Soc.
1998, 120, 5080. (b) Guo, R.; Li, X.; Wu, J.; Kwok, W. H.; Chen, J.; Choi,
M. C. K.; Chan, A. S. C. Tetrahedron Lett. 2002, 43, 6803.
(19) Uehara, A.; Kubota, T.; Tsuchiya, R. Chem. Lett. 1983, 441.
4714
Org. Lett., Vol. 10, No. 21, 2008