Axial [6,6′-(2,4-pentadioxy)]-1,1′-biphenyl-2,2′-diamine (PD-BIPHAM): practical synthesis and applications in asymmetric hydrogenation

Article abstract of DOI:10.1016/j.tet.2010.03.073

A rapid, reliable, and atom-economical procedure for the novel axially biphenyl diamine, (R,R,S_ax)-PD-BIPHAM 1, has been developed successfully by using highly efficient central-to-axial transformation strategy. The attractive feature of this m

Full text of DOI:10.1016/j.tet.2010.03.073

Tetrahedron 66 (2010) 3702–3706
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Axial [6,60-(2,4-pentadioxy)]-1,10-biphenyl-2,20-diamine (PD-BIPHAM): practical
synthesis and applications in asymmetric hydrogenation
,
b
,
a
c
a
Chun-Jiang Wang a , Zhong-Ping Xu , Xiang Wang , Huai-Long Teng
*
a College of Chemistry and Molecular Sciences, Wuhan University, Hubei Province, 430072, PR China
b State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjing, 300071, PR China
c School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan, Hubei Province, 430073 PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A rapid, reliable, and atom-economical procedure for the novel axially biphenyl diamine, (R,R,Sax)-
PD-BIPHAM 1, has been developed successfully by using highly efficient central-to-axial transformation
strategy. The attractive feature of this methodology is that no tedious resolution was needed. The
effectiveness of this new chiral skeleton was initially demonstrated by highly enantioselective hydro-
Received 21 January 2010
Received in revised form 16 March 2010
Accepted 19 March 2010
Available online 24 March 2010
genation of a-dehydroamino acid esters.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Axial biphenyl diamine
Central chirality
Axial chirality
PD-BIPHAM
Asymmetric hydrogenation
1. Introduction
sufficiently as an axial scaffold. Therefore, the development of a new
and practical atropisomeric biphenyl diamine is in high demand.
Catalytic asymmetric reaction is one of the most powerful
methods for the synthesis of enantiomerically enriched products,
and ligand design based on chiral backbone plays a crucial role in
this area.1 Among many successful chiral skeletons, atropisomeric
biaryl backbones, most notably 1,10-binaphthalene derivatives (e.g.,
BINOL, BINAP, BINAM, and NOBIN),2 occupy a prominent position in
asymmetric synthesis (Fig. 1). 1,10-Binaphthyl-2,20-diamine (abbre-
viated to BINAM), the commercially available but restrictively ex-
pensive chiral binaphthalene diamine, and has found widespread
uses in many metal-catalyzed2d,3 or organo-catalyzed4 asymmetric
reactions in the past decades. Comparing to the widely used
binaphthalene counterpart, much less attention has beenpaid to the
similarly atropisomeric biphenyl backbond although the steric and
electronic properties of such skeleton are more easily modified.5
One biphenyl diamine, 6,60-dimethyl-biphenyl-2,20-diamine
(abbreviated to BIPHAM) was synthesized early in 1927,6 however,
only limited applications in asymmetric catalysis have been repor-
ted probably due to its unpractical and exhaustive fractional
resolution procedures.7 Although BIPHAM has also been commer-
cialized, the higher cost prevents it from being investigated
O
NH
NH
NH
NH
NH
NH
2
2
2
2
2
2
O
(R,R,S )-PD-BIPHAM
ax
6,6'-dimethyl-biphenyl-
2,2'-diamine (BIPHAM)
BINAM
Figure 1. Atropisomeric biaryl diamine: BINAM, 6,60-dimethyl-biphenyl-2,20 diamine
and the newly designed (R,R,Sax)-PD-BIPHAM.
Herein, we reported the concise synthesis of a new type of
atropisomeric biphenyl diamine: (Sax)-[6,60-(2R,4R-pentadioxy)]-
1,10-biphenyl-2,20-diamine (abbreviated to (R,R,Sax)-PD-BIPHAM)
through central-to-axial chirality transformation strategy, and the
asymmetric inductive efficiency of the new chiral biphenyl diamine
backbone was demonstrated through highly efficient asymmetric
hydrogenation with bis(aminophosphine) ligands derived from
(R,R,Sax)-PD-BIPHAM.8
2. Results and discussion
The conceptual diastereoselective intramolecular Ullmann
coupling of two aryl units, pre-fixed through chiral tether,9 is
* Corresponding author. Tel.: þ86 27 68754067; fax: þ86 27 65241880; e-mail
address: cjwang@whu.edu.cn (C.-J. Wang).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.03.073

C.-J. Wang et al. / Tetrahedron 66 (2010) 3702–3706
3703
a popular and appealing strategy in the synthesis of atropiso-
meric biaryl compounds since it avoids the time-consuming and
tedious resolution for obtaining the enantiomerically pure
compounds. Highly efficient central-to-axial chirality trans-
formation (up to 99% de) has been realized through various chiral
diols and 1,2-amino alcohols,9a and it has also been successfully
demonstrated for constructing several atropisomeric diphos-
phine ligands, such as NAPhenPhos,10 PQ-Phos,11 and C3*-tune-
phos,12 in which the commercially available chiral (S,S)- or (R,R)-
2,4-pentanediol was used as the central chiral bridge and re-
markably high diaselectivities were achieved. Inspired by the
aforementioned research works, we envisioned that the central-
to-axial chirality transformation strategy would facilitate syn-
thesizing atropisomeric diamine without extra resolution, and
thereby present more efficient and practical synthetic method
for the biphenyl diamine. To the best of our knowledge, this
strategy has not been reported for the synthesis of atropisomeric
diamine so far.8
compound 6 and therefore 98.5:1.5 diastereoselectivity was
generated in the key Ullmann coupling reaction, that is, the
diastereoselective differentiation was highly controlled for this
copper-mediate intramolecular Ullmann coupling even at 120 ꢀC.
To our delight, the enantiopure dinitro compound 5 (>99% de)
can be easily achieved by simple crystallization of the crude
product. Finally, reductive hydrogenation of enantiomerically
pure 5 in the presence of catalytic amount of Pd/C afforded the
desired atropisomeric (R,R,Sax)-PD-BIPHAM 1 in quantitative
yield (Scheme 1). Finally, reductive hydrogenation of enantio-
merically pure 5 in the presence of catalytic amount of Pd/C
afforded the desired atropisomeric (R,R,Sax)-PD-BIPHAM 1 in
quantitative yield.
O
i) BBr , DCM
3
MeO
MeO
NO
NO
NO
NO
2
2
2
2
ii) MeI/K CO , DMF
2
3
O
The concise synthetic route of atropisomeric (R,R,Sax)-PD-
BIPHAM 1 is depicted in Scheme 1. The chiral dinitro compound 4
containing central stereogenic linkage was prepared by Mitsu-
nobu reaction with (2S,4S)-pentanediol 2 and 3-nitro-2-iodo-
phenol 3.13 Both enantiomers of (2S,4S) and (2R,4R)-pentanediol
are commercially available or easily obtained through Ru-BINAP-
catalyzed asymmetric hydrogenation of inexpensive starting
material 2,4-pentandione.14 The double Mitsunobu reaction
proceeded smoothly and afforded (2R,4R)-4 in 86% yield within
(S )-6
ax
(R,R,S )-5
ax
Scheme 2. Diastereoselectivity determination of intramolecular Ullmann Coupling
through HPLC analysis of the known compound (Sax)-6.
To determine the absolute axial chirality of the biaryl moiety
of 5 and 1, 3,30,5,50-tetrakis-bromo-PD-BIPHAM 7 was synthe-
sized from PD-BIPHAM through highly efficient and simple bro-
mination protocol, which also verifies the easily modification
property of biphenyl backbones mentioned before (Scheme 3). A
X-ray analysis of crystal of 7 revealed Sax configuration for axial
biphenyl moiety and (2R,4R) configuration for the two central
chirality therefore also for the corresponding moiety in 5 and 1
(Fig. 2).17
2 h as
a
single diastereoisomer.15 Alternatively, the linked
(2R,4R)-4 could be also achieved in little lower yield through
reaction (2S,4S)-pentanediol di-p-tosylate with 3-nitro-2-iodo-
phenol in the presence of K2CO3 in DMF (see Experimental
section). The linked central stereogenic (2R,4R)-4 underwent
copper-mediate intramolecular Ullmann coupling to generate the
corresponding atropisomeric dinitro compound (R,R,Sax)-5 in 75%
yield.
Br
O
Br
O
O
Br
2
NH
NH
NH
NH
2
2
2
2
HOAc
98% yield
NO2
O
OH
OH
O
O
I
I
DEAD, PPh3
Br
Br
+
HO
NO2
(R,R,S )-1
(R,R,S )-7
ax
THF
86% yield
ax
I
3
Scheme 3. Synthesis of (R,R,Sax)-30,30,5,50-tetrakis-bromo-PD-BIPHAM 7.
2
NO2
(R,R)-4
With enantiopure (R,R,Sax)-PD-BIPHAM 1 in hand, we extended
its application to the synthesis of bis(aminophosphine) ligands 8.
O
O
O
Cu, DMF
75% yield
Pd/C, H2
99% yield
NO2
NO2
NH2
NH2
O
(R,R,Sax)-5
(R,R,Sax)-1
Scheme 1. Synthesis of atropisomeric diamine (R,R,Sax)-PD-BIPHAM
1
through
central-to-axial chirality transformation strategy.
In order to determine the diastereoselectivity of the key
intramolecular Ullmann coupling step, the crude dinitro com-
pound 5, after removing the copper salts, were treated with BBr3
followed by methylation with MeI/K2CO3 in DMF to generate the
known compound 616 (Scheme 2). Note that upon cleavage of the
chiral linkage embedded in the crude compound 5, any mixture
of diastereomers with respect to the assured central chirality
(2R,4R) and the axial chirality formed in the intramolecular
Ullmann coupling reaction would now become a mixture of
enantiomers with respect to the axial chirality. According to
HPLC analysis, up to 97% ee was determined for the derived
Figure 2. X-ray crystal structure of (R,R,Sax)-7.

3704
C.-J. Wang et al. / Tetrahedron 66 (2010) 3702–3706
As shown in Scheme 4, the chiral ligand was conveniently obtained
in good yield by the reaction of (R,R,Sax)-PD-BIPHAM 1 with PPh2Cl
in the presence of Et3N and catalytic amount of DMAP.
atom-economical procedure for axially biphenyl diamine without
tedious resolution and diversifies the family of chiral axially chiral
biphenyl backbones. The effectiveness of this new chiral skeleton
was demonstrated by highly efficient asymmetric hydrogenation
of
a-dehydroamino acid esters with the chiral bis(aminophos-
O
O
O
O
phine) ligand derived from (R,R,Sax)-PD-BIPHAM. Further in-
vestigations of this new axially biphenyl diamine in asymmetric
catalysis are underway in our laboratory and will be reported in
due course.
PPh2Cl, Et3N
DMAP, DCM
NH2
NH2
NHPPh2
NHPPh2
(R,R,Sax)-1
(R,R,Sax)-8
4. Experimental section
4.1. General remarks
Scheme 4. Synthesis of the bis(aminophosphine) (R,R,Sax)-8.
The catalytic performance of bis(aminophosphine) 8 was tested
in the Rh(I)-catalyzed asymmetric hydrogenation18 of
-dehy-
a
All reactions were carried out using standard Schlenk tech-
niques unless specified other otherwise. The degassed dry solvents
are used throughout each experiment. 1H NMR spectra were
recorded on a VARIAN Mercury 300 MHz spectrometer in chloro-
form-d. Chemical shifts are reported in parts per million with the
internal TMS signal at 0.0 ppm as a standard. The data are reported
as (s¼singlet, d¼doublet, t¼triplet, q¼quartet, m¼multiplet or
unresolved, br s¼broad singlet, coupling constant(s) in Hz, in-
tegration). 13C NMR spectra were recorded on a VARIAN Mercury
75 MHz spectrometer in chloroform-d. Chemical shifts are reported
in parts per million with the internal chloroform signal at 77.0 ppm
as a standard. 31P NMR spectra were recorded on a VARIAN Inova-
600 MHz spectrometer in chloroform-d, chemical shifts are repor-
ted in parts per million with the external 85% H3PO4 signal at
0.0 ppm as a standard. Commercially obtained reagents were used
without further purification. All reactions were monitored by TLC
with silica gel-coated plates. Enantiomeric ratios were determined
by chiral HPLC using a chiralpak AD-H column with hexane and
i-PrOH as solvents, or determined by chiral GC using a Supelco
droamino acid esters 9, and the results are summarized in Table 1. A
wide array of ring substituted phenylalanine derivatives 10 were
formed with excellent enantioselectivities, regardless of the posi-
tion and the electronic property of the substituents on the phenyl
ring, which demonstrates the asymmetric inductive efficiency of
the new chiral biphenyl diamine backbone. Compared with the
results achieved by (R)-BDPAB (L1) derived from (R)-1,10-
binaphthyl-2,20-diamine19 and similar ligand (L2) derived from
(S)-6,60-dimethoxyl-1,10-biphenyl-2,20-diamine, our catalyst sys-
tem shows much higher enantioselectivities.20
Table 1
Rh-catalyzed asymmetric hydrogenation of (Z)-acetamido-3-arylacrylic acid methyl
estersa
COOMe
[Rh(COD) ]BF /8 (0.5 mol%)
COOMe
NHAc
9
2
4
*
R
R
H
(10 atm), THF, rt
NHAc
10
2
Entry
Substrate
R
ee (%)
chiral Select 1000 or a Chirasil-L-Val column. The absoluted con-
(R)-L1b
(S)-L2c
(R,R,Sax)-8d
figurations of the known products were determined by comparing
the GC or HPLC retention times with the reported data. 3-Nitro-2-
iodophenol13 and (2S,4S)-pentanediol14 was prepared by the
reported synthetic methods.
1
2
3
4
5
6
7
8
9a
9b
9c
9d
9e
9f
9g
9h
9i
Ph
90
74
d
71
72
72
74
d
73
73
d
d
96
96
96
97
94
93
96
96
95
94
95
o-Me–Ph
p-Me–Ph
o-Cl–Ph
m-Cl–Ph
p-Cl–Ph
o-MeO–Ph
p-MeO–Ph
p-F–Ph
d
95
90
90
88
d
d
d
d
93
4.1.1. Synthesis of (R,R)-4.
OH OH
9
10
11
, DEAD, PPh
o
3
9j
9k
2-Naphthyl
H
THF, 0 C to rt
NO
2
86% yield
A
O
O
I
I
(R,R)-4
HO
NO
2
O
O
NHPPh2
NHPPh2
NHPPh2
NHPPh2
MeO
MeO
NHPPh2
NHPPh2
I
3
B
OTs OTs
DMF, 80
NO
2
, K CO
2
3
o
C
(R)-BDPAB (L1)
(S)-DMBDPPABD (L2)
(R,R,Sax)-8
70% yield
a
In all cases, full conversion was achieved with (R,R,Sax)-8 as chiral ligand.
The data were reported by Chan under 30 psi hydrogenation in THF using (R)-
Method A: To
a solution of 2-iodo-3-nitrophenol (1.65 g,
b
6.24 mmol), (2S,4S)-pentane-2,4-diol (0.31 g, 3.0 mmol), and tri-
phenylphosphine (1.63 g, 6.24 mmol) in 10 mL THF, a solution of
diethyl azodicarboxylate (1.09 g, 62.4 mmol) in 5 mL THF was
added at 0 ꢀC. The mixture was gradually warmed up to room
temperature. The reaction was completed in additional 6 h. The
solvent was removed in vacuum, and the residue was subjected to
BDPAB (L1) as chiral ligand, see: Ref. 19a.
c
The date were reported by Chen under 0.68 MPa in acetone using
(S)-DMBDPPABD (L2) as chiral ligand, see: Ref. 20.
d
Enantiomeric excesses were determined by GC. The absolute configuration of
the products was determined as S by comparing the retention times with the
reported data in the literatures.
flash silica gel chromatography to afford 4 in 86% yield. Mp 80 ꢀC;
25
3. Conclusions
[a
]
ꢁ192.8 (c 0.98, CHCl3); IR (KBr)
n
2978, 2092, 1642, 1583, 1450,
1H NMR (CDCl3,
7.23 (dd, J¼7.2, 7.8 Hz, 2H), 7.09 (d, J¼7.2 Hz, 2H),
D
1355, 1272, 1144, 1109, 1019, 844, 790, 734 cmꢁ1
TMS, 300 MHz)
6.83 (d, J¼7.8 Hz, 2H), 4.89–4.82 (m, 2H), 2.15 (m, 2H), 1.45 (d,
;
In summary, the atropisomeric PD-BIPHAM is designed and
prepared successfully for the first time by using central-to-axial
transformation strategy, which presents a rapid, reliable and
d
J¼6.0 Hz, 6H); 13C NMR (CDCl3, TMS, 75 MHz)
d 158.16, 155.59,

C.-J. Wang et al. / Tetrahedron 66 (2010) 3702–3706
3705
130.33, 116.89, 115.97, 81.36, 73.98, 44.78, 20.34; HRMS calcd for
C17H16I2N2O6: 597.9098, found: 597.9099.
(dd, J¼7.2, 7.8 Hz, 2H), 6.55 (d, J¼7.8 Hz, 2H), 6.48 (d, J¼7.2 Hz,
2H), 4.57–4.51(m, 2H), 1.80 (m, 2H), 1.32(d, J¼6.3 Hz, 6H); 13C
Method B: To a solution of 2-iodo-3-nitrophenol (1.06 g,
4 mmol) in dry 10 mL DMF, K2CO3 (1.1 g, 8 mmol) was added.
The mixture was stirred for 4 h. A solution of (2S,4S)-2,4-pen-
tanediol di-p-toluenesulfonate (0.91 g, 2.2 mmol) in 10 mL dry
DMF was added. The mixture was stirred at 80 ꢀC for 4 h. The
reaction mixture was poured into ice-water, and then extracted
with ether. The combined organic layers were dried over
Na2SO4. The solvent was removed in vacuum, and the residue
was subjected to flash silica gel chromatography to afford 4 in
70% yield.
NMR (CDCl3, TMS, 75 MHz) d 159.10, 145.55, 129.24, 113.37, 110.29,
108.11, 75.21, 41.18, 22.54; HRMS calcd for C17H20N2O2: 284.1525,
found: 284.1522.
4.2.2. Synthesis of 7. To a solution of (R,R,Sax)-1 (0.568 g, 2.0 mol) in
15 mL AcOH was added Br2 (1.41 g, 8.8 mol) in 10 mL AcOH drop-
wise, and then the reaction mixture was stirred at room tempera-
ture for 3 h. The reaction mixture was poured into ice-water, and
then extracted with DCM. The combined organic layers were dried
over Na2SO4. The solvent was removed in vacuum, and the residue
was subjected to flash silica gel chromatography to obtain 7 in 98%
25
4.1.2. Synthesis of 5. To a solution of 4 (3.60 g, 6.0 mmol) in 35 mL
dry DMF was added copper powder (1.52 g, 24.0 mmol). The mix-
ture was heated at 120 ꢀC until the reaction was completed. After
DMF was removed in vacuum, the residue was dissolved in DCM,
and then washed with water and brine. The organic layer was dried
over Na2SO4. The solvent was removed in vacuum, and the residue
was subjected to flash silica gel chromatography to afford 5 in 75%
yield and 97% diastereoselectivity. The enantiopure dinitro com-
yield. [
a
]
þ215.4 (c 1.48, CHCl3); IR (KBr)
n 3363, 2973, 2933.5,
D
2100.1, 1623, 1455, 1376, 1004, 1250, 1113, 1091, 1005, 900, 784, 744,
721 cmꢁ1 1H NMR (CDCl3, TMS, 300 MHz)
; d 7.64 (s, 2H), 4.92 (m,
2H), 1.73 (m, 2H), 1.28 (d, J¼5.7 Hz, 6H); 13C NMR (CDCl3, TMS,
75 MHz)
d 153.50, 142.46, 136.07, 116.88, 104.38, 103.33, 74.38,
40.80, 21.57; HRMS calcd for C17H16Br4N2O2: 595.7945, found:
595.7947.
pound 5 (>99% de) can be easily achieved by simple crystallization
25
4.3. Procedure for the preparation of (R,R,Sax)-8
of the crude product in CHCl3. Mp 264 ꢀC; [
a
]
þ567.2 (c 1.17,
D
CHCl3); IR (KBr)
n
2933, 1633, 1528, 1444, 1344, 1270, 1194, 1159,
1086, 979, 892, 813, 743 cmꢁ1
;
1H NMR (CDCl3, TMS, 300 MHz)
To
a solution of (R,R,Sax)-1 (0.10 g, 0.352 mmol), Et3N
(0.28 g, 0.40 mL, 2.77 mmol), and DMAP (12 mg, 0.098 mmol)
in 3 mL DCM was added Ph2PCl (0.186 g, 0.85 mmol) at 0 ꢀC.
The reaction mixture was then allowed to warm to ambient
temperature and stirred overnight. The solvent was removed
under vacuum, and the crude product was purified through
d
7.91 (d, J¼7.5 Hz, 2H), 7.52 (dd, J¼7.5, 7.8 Hz, 2H), 7.41 (d, J¼7.8 Hz,
2H), 4.61 (m, 2H), 1.80 (m, 2H), 1.34 (d, J¼6.0 Hz, 6H); 13C NMR
(CDCl3, TMS, 75 MHz) d 157.82, 148.76, 129.56, 123.50, 119.15, 77.03,
39.98, 21.90; HRMS calcd for C17H16N2O6: 344.1008, found:
344.1012.
a basic alumina column to afford (R,R,Sax)-8 as white solid in
25
85% yield. [
a
]
þ88.9 (c 0.94, CHCl3); IR (KBr)
n 3366, 2676,
D
4.2. Diastereoselectivity determination of the intramolecular
Ullmann Coupling step
2927, 2095, 1644, 1592, 1575, 1453, 1433, 1375, 1289, 1250,
1089, 1032, 739, 695 cmꢁ1
phosphorous decoupled)
;
1H NMR (CDCl3, TMS, 300 MHz,
7.25–7.13 (m, 22H), 7.03 (d,
d
To a solution of (R,R,Sax)-5 (69 mg, 0.2 mmol) in 5 mL dry
dichloromethane was added BBr3 (50 mL, 0.5 mmol) at ꢁ78 ꢀC,
and the solution was stirred for 1 h. The mixture was quenched
with 2 N HCl. The water layer was extracted with ether. The
combined organic layers were dried over Na2SO4 and evapo-
rated to afford a yellow solid. The yellow solid was dissolved in
3 mL DMF, K2CO3 (212 mg, 2.0 mmol) and CH3I (170 mg,
1.2 mmol) were added, and then the mixture was heated at
80 ꢀC for 48 h. The reaction mixture was poured into ice-water,
and then extracted with ether. The combined organic layers
were dried over Na2SO4. The solvent was removed in vacuum,
and the residue was subjected to flash silica gel chromatog-
raphy to afford the known compound 6 in 97% yield. The
product 6 was analyzed by HPLC to determine the diaster-
eoselectivity of the intramolecular Ullmann Coupling reaction
(Chiralcel AD-H, i-propanol/hexane¼3:97, flow rate 1.0 mL/min,
J¼6.6 Hz, 2H), 6.64 (d, J¼7.8 Hz, 2H), 4.61 (m, J¼6.9 Hz, 2H),
1.79 (m, 2H), 1.33 (d, J¼6.6 Hz, 6H); 13C NMR (CDCl3, TMS,
75 MHz, phosphorous decoupled)
d 153.63, 140.29, 135.68,
134.17, 126.14, 125.22, 124.25, 123.65, 123.09, 110.26, 104.89,
104.41, 69.99, 35.70, 17.11; 31P NMR (CDCl3, 85% H3PO4,
242.86 MHz)
d
32.257; HRMS calcd for C41H38N2O2P2:
652.2409, found: 652.2411.
4.4. Procedure for the preparation of [Rh(8)(COD)]BF4
[Rh(COD)2]BF4 (32.6 mg, 0.080 mmol) and chiral bisamino-
phosphine ligand (R,R,Sax)-8 (54.9 mg, 0.084 mmol) was dissolved
in 2 mL degassed CH2Cl2 in a Schlenk tube under N2 at room
temperature. The resulting mixture was stirred at ambient tem-
perature for 2 h. The solvent was removed under vacuum to afford
[Rh(8)(COD)]BF4 as an orange solid, which was used as the catalyst
without further purification. 31P NMR (CDCl3, 85% H3PO4,
l
¼254 nm): 99.8% ee, tmajor¼32.2 min, tminor¼48.9 min. 1H NMR
(CDCl3, TMS, 300 MHz)
d
7.75 (d, J¼7.2 Hz, 2H), 7.50 (dd, J¼7.2,
8.1 Hz, 2H), 7.19 (d, J¼8.1 Hz, 2H), 3.72 (s, 6H); 13C NMR (CDCl3,
242.86 MHz)
d
68.645 (d, JRh–P¼249.2 Hz).
TMS, 75 MHz)
56.33.
d 156.56, 149.03, 29.28, 118.32, 116.33, 115.33,
4.5. Representative experimental procedure for the
asymmetric hydrogenation
4.2.1. Synthesis of (R,R,Sax)-1. To a solution of 5 (5.0 g, 14.5 mmol)
in 80 mL methanol was added Pd/C (0.5 g) in autoclave, into
which hydrogen gas was charged at the desired pressure (60 bar).
The mixture was stirred overnight at 50 ꢀC, and then the hydro-
gen was released carefully. The mixture was filtered and the
solvent was removed under reduced pressure. The residue was
[Rh(8)(COD)]BF4 (10.0 mg, 0.01 mmol) was dissolved in
degassed THF (8 mL) in a glovebox, and distributed equally to four
vials. To the catalyst solution was added substrate (0.5 mmol). All
the vials were placed together in a steel autoclave into which hy-
drogen gas was charged at the desired pressure. After stirring at
room temperature for 2 h, the hydrogen was released carefully and
the solution was concentrated. The residue was purified by column
chromatography to give the corresponding hydrogenation product,
subjected to flash silica gel chromatography to give (R,R,Sax)-1 in
25
99% yield. Mp 100 ꢀC; [
a
]
þ298.5 (c 1.02, CHCl3); IR (KBr)
n 3363,
D
2973, 2933, 2100, 1623, 1455, 1376, 1004, 1250, 1113, 1091, 1005,
900, 784, 744, 721 cmꢁ1 1H NMR (CDCl3, TMS, 300 MHz)
7.11
;
d

3706
C.-J. Wang et al. / Tetrahedron 66 (2010) 3702–3706
Wynn, T. J. Am. Chem. Soc. 2001, 123, 6199; (n) Denmark, S. E.; Fan, Y. J. Am.
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mizu, H.; Nagasaki, I.; Saito, T. Tetrahedron 2005, 61, 5405.
which was then directly analyzed by chiral GC to determine the
enantiomeric excess.
6. Meisenheimer, J.; Hoering, M. Chem. Ber. 1927, 60, 1425.
Acknowledgements
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This work was supported by National Natural Science Founda-
tion of China (20642005, 20702039), State Key Laboratory of
Elemento-organic Chemistry and Wuhan University. We thank Prof.
Yuepeng Cai in South China Normal University for solving the
crystal structure.
Supplementary data
Spectroscopic data of compounds 1–8. Supplementary data
associated with this article can be found, in the online version, at
doi:10.1016/j.tet.2010.03.073.
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