Efficient bimetallic titanium catalyst for carbonyl-ene reaction

Article abstract of DOI:10.1016/j.tetlet.2009.09.078

A new family of achiral 3,3′,5,5′-tetrasubstituted-2,2′,6,6′-tetrahydroxy biphenyl ligand 4 was developed. The axial chirality of the ligand could be induced by the chelation of 2,2′,6,6′-tetrahydroxy groups with (R)-BINOL-Ti(OⁱPr)₂

Full text of DOI:10.1016/j.tetlet.2009.09.078

Tetrahedron Letters 50 (2009) 6672–6675
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Efficient bimetallic titanium catalyst for carbonyl-ene reaction
Fang Fang, Fang Xie, Han Yu, Hui Zhang, Bo Yang, Wanbin Zhang *
School of Chemistry and Chemical Technology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
a r t i c l e i n f o
a b s t r a c t
0
0
0
0
Article history:
A new family of achiral 3,3 ,5,5 -tetrasubstituted-2,2 ,6,6 -tetrahydroxy biphenyl ligand 4 was developed.
Received 12 August 2009
Revised 11 September 2009
Accepted 15 September 2009
Available online 18 September 2009
0
0
The axial chirality of the ligand could be induced by the chelation of 2,2 ,6,6 -tetrahydroxy groups with
i
(
R)-BINOL-Ti(O Pr)
2
to form an axially chiral bimetallic titanium catalyst 9. Compared with (R)-BINOL-
Ti(O Pr) catalyst, this novel catalyst 9 exhibited excellent activity and enantioselectivity for the
carbonyl-ene reaction of methylstyrene and ethyl glyoxylate. 3,3 ,5,5 -Tetrasubstituted groups showed
a remarkable effect on both enantioselectivity and yield. With 9d prepared from 3,3 ,5,5 -tetramethyl-
,2 ,6,6 -tetrahydroxy biphenyl 4d as the catalyst, the best result, up to 97.6% ee and 99% yield, was
obtained. Additionally, the bimetallic catalyst 9 also showed better catalytic capability than the
corresponding monometallic catalyst.
i
2
0
0
0
0
Keywords:
0
0
2
Bimetallic titanium catalyst
0
0
0
0
3
,3 ,5,5 -Tetrasubstituted-2,2 ,6,6 -
tetrahydroxy biphenyl
Carbonyl-ene reaction
Ó 2009 Elsevier Ltd. All rights reserved.
The design and development of novel and effective chiral
ligands for enantioselective reactions are of the fundamental
aspects in asymmetric catalysis, and have attracted a great deal
of attention from both academic research and industry. Thousands
of ligands with various chiral elements have been developed and
applied in many catalytic asymmetric reactions to produce enanti-
omerically pure compounds.1
Among them, axial chirality is one of the important stereogenic
elements used for the development of chiral ligands.2 In general,
there are two necessary preconditions for axial chirality in biaryl
molecules, that is, a rotationally stable biaryl axis and the presence
of different ortho substituents on both sides of the biaryl axis.
Recently, we are interested in a new family of axially achiral
biaryl, which has four constitutionally identical substituents
groups at the ortho positions of the biphenyl axis. This type of mol-
because of the different energies of the two diastereomers. These
chiral bimetallic complexes would provide new reactivity patterns
and physical properties that could not be achieved with similar
monometallic complexes, and neighboring metal ions would be ex-
4
pected to cooperate in promoting the reaction.
With this axial chiral catalyst design concept of the former case
(Fig. 1, 2), we have successfully developed a new family of tetraox-
azolinyl biphenyl ligands, in which a chiral element was intro-
duced in the oxazoline coordination group. When they chelated
with Pd(II), a stable axial chirality of the biphenyl backbone was in-
duced and only one of the two diastereomer complexes was
formed. This chelation-induced axially chiral Palladium complex
system with tetraoxazoline ligands showed excellent catalytic
activities and enantioselectivities in the Wacker-type cyclizations.5
Herein, using our axial chiral catalyst design concept of the later
case mentioned above (Fig. 1, 3), we would like to report a new
family of achiral ortho-tetrahydroxy biphenyl ligand 4 (Fig. 2)
and its complexation and application to the enantioselective
2
ecule has three C symmetric factors in its structure, but no axial
chirality due to the molecular symmetry. However, when the four
identical substituents are linked pairwise by two bridges, the axial
chirality of the molecule is induced, so a pair of enantiomers is
0
0
carbonyl-ene reactions. Since four substituted groups at 3,3 ,5,5 -
positions are near the metal reaction center, when 4 is complexed
to metal ion, the bimetallic catalyst so formed (Fig. 1, 3) is
expected to have a better effect on catalytic activities and
enantioselectivities.
formed, which is different from traditional axially chiral molecules
3
(
Fig. 1, 1). If the four substituents are of the coordination group
and coordinated to metal ions, one pair of enantiomeric complexes
would be formed. If we introduce a chiral element in the four coor-
dination groups (Fig. 1, 2) or an additional chiral ligand (Fig. 1, 3) to
the metal ions, one of the two possible diastereomeric bimetallic
complexes with different axial chirality in biphenyl backbone
should be formed in preference to the other, and in some cases,
only one of the two bimetallic diastereomers might be formed
Achiral ligand 4 can be readily prepared. 4a, 4b, and 4e were
6
0
0
0
0
prepared as reported methods. 3,3 ,5,5 -Tetrabromo-2,2 ,6,6 -tet-
rahydroxy biphenyl 4c was readily synthesized as following
0
0
(Scheme 1): bromation of 2,2 ,6,6 -tetramethoxy biphenyl with
Br (4.4 equiv) in the presence of HOAc (0.3 equiv) gave bromized
compound 5 in quantitative yield. Then, 3,3 ,5,5 -tetrabromo-
2
7
0
0
0
0
8
2
,2 ,6,6 -tetrahydroxy biphenyl 4c was obtained by the deprotec-
*
Corresponding author. Tel./fax: +86 21 5474 3265.
E-mail address: wanbin@sjtu.edu.cn (W. Zhang).
tion of 5 with BBr (4.4 equiv) in quantitative yield.
3
0
040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.09.078

F. Fang et al. / Tetrahedron Letters 50 (2009) 6672–6675
6673
C2
C2
C2
A
A
A
A
L
*
L*
L
L
L
L
*
L
C2
C2
C2
C2
C2
C2
*L
L*
*
L*
L'
L'
L
L
L
L'
A
A
A
A
A
A
+
M
M
*
*
M
*
M
*
A
A
L*
L
L'
L
1
2
3
Figure 1. The inducement of the axial chirality of the axially achiral biaryl.
R
R
Cl
Cl
OCH3
H CO
OCH3
H CO
3
3
HO
OH
OH
CH O / HOAc / HCl / H PO
2
3
4
H CO
OCH3
100 ºC, 10 h, 94%
H CO
OCH3
Cl
3
3
HO
Cl
R
R
6
4a-e
R = H, Cl, Br, Me, Et
H CO
OCH3
OCH3
HO
HO
OH
OH
NaBH4 / DMSO
rt., 2 h, 99%
3
BBr3 / CH2Cl2
-78 ºC, 2 h, 100%
Figure 2. Axially achiral ortho-tetrahydroxy biphenyl ligands 4a–e.
H3CO
0
0
0
0
Preparation of the 3,3 ,5,5 -tetramethyl-2,2 ,6,6 -tetrahydroxy
7
4d
biphenyl 4d was as following (Scheme 2): firstly, chloromethyla-
0
0
Scheme 2. The synthesis of ligand 4d.
tion of 2,2 ,6,6 -tetramethoxy biphenyl with paraformaldehyde
30 equiv) in the mixture acid of phosphoric acid, concentrated
hydrochloric acid, and acetic acid (V = 1:1:1, 0.01 M) afforded
product 6 with 94% isolated yield. Then, reduction of 6 by NaBH
gave 3,3 ,5,5 -tetramethylated compound 7 in 99% yield. After the
(
9
R
R
4
0
0
10
i
HO
OH
OH
O
O
OPr
toluene / ether
60 ºC, 0.5 h
deprotection of 7 with BBr
titative yield.
3
(4.4 equiv), 4d11 was obtained in quan-
+
Ti
i
HO
R
OPr
Then we investigated the complexation of 4 with Ti(IV). When 4
i
R
was added to 2 equiv (R)-BINOL-Ti(O Pr)
2
and stirred at 60 °C for
.5 h, 2,2 ,6,6 -tetrahydroxy groups were linked pairwise by chela-
tion with metal Ti to give the compound 9 with bimetallic struc-
0
0
4a-e
0
8
R
R
1
2
L
L
ture (Scheme 3).
Then this new catalyst 9 prepared from the addition of axial
O
O
O
O
O
O
O
i
Ti
L
Ti
L
2
achiral biphenyl 4 to (R)-BINOL-Ti(O Pr) was evaluated by the
O
carbonyl-ene reaction (Scheme 4),13 since it was reported by
Mikami that dramatic increases in both yields and the ees could
R
R
be obtained by the addition of optically active ligands such as
9a-e
i
(
R)-BINOL to the (R)-BINOL-Ti(O Pr)
2
catalyst compared with no
R = H, Cl, Br, Me, Et
1
4
addition or addition of racemic ligands such as (±)-BINOL.
L = iPrOH
i
4
Thus, (R)-BINOL and Ti(O Pr) (molar ratio = 1:1) were stirred in
0
0
Scheme 3. The synthesis of the axially chiral bimetallic titanium catalysts 9a–e.
dry toluene at rt for 30 min, and then, to this mixture 2,2 ,6,6 -tet-
Br
Br
Br
Br
H CO
OCH3
OCH3
H CO
OCH3
HO
OH
3
3
Br / HOAc
rt., 3 h, 100%
BBr / CH Cl
3 2 2
2
-78 ºC, 2 h, 100%
H CO
H CO
OCH3
Br
HO
Br
OH
Br
3
3
Br
5
4c
Scheme 1. The synthesis of ligand 4c.

6
674
F. Fang et al. / Tetrahedron Letters 50 (2009) 6672–6675
O
OH
9
(5 mol%)
L
O
O
+
O
O
O
O
OH
OH
H
Et
Ph
Et
Ph
Toluene
Ti
O
11
O
10
12
L
Scheme 4. The carbonyl-ene reaction catalyzed by the axially chiral bimetallic
titanium catalyst 9a–e.
L = iPrOH
13d
Figure 3. The axially chiral monometallic titanium catalyst 13d.
rahydroxy biphenyl 4 (0.5 equiv) resolved in dry ether was added,
and stirred for another 0.5 h at 60 °C. At 0 °C,
a-methylstyrene 10
(
10 equiv) and freshly distilled ethyl glyoxylate 11 (20 equiv) were
added and stirred at 0 °C for 30 h. The results of the experiment
R
R
R
O
R
showed that bimetallic catalyst 9 showed higher enantioselectivity
L
HO
OH
i
O
O
OH
OH
i
(R)-BINOL-Ti(OPr)
and activity than catalyst (R)-BINOL-Ti(O Pr)
1
2
(Table 1, entries
2
Ti
L
0
0
–6), and the introduction of sterically bulky 3,3 ,5,5 -tetrasubstit-
HO
R
OH
O
R
uents had a remarkable effect on enantioselectivity or/and yield
Table 1, entries 2–6). The yields of the reaction were advanced
dramatically except 9c and 9e, which were presumed to be too
R
R
(
4
R,R-13
0
0
R
O
R
bulky in 3,3 ,5,5 -positions and decreased the activity of the reac-
0
0
L
L
tion. When 9d containing 3,3 ,5,5 -tetramethyl groups was used,
2 was obtained with the best result in 97.6% ee and 99% yield
Table 1, entry 5).
Furthermore, addition of (R)-BINOL-Ti(O Pr)
i
O
O
O
O
(
R)-BINOL-Ti(OPr)2
1
Ti
Ti
L
(
O
R
O
O
i
L
2
to 4d with the
R
molar ratio of 1:1 formed the monometallic catalyst 13d (Fig. 3),
with which catalyst, 96.1% ee and 90% yield were obtained (Table
R,R,R-9
1
, entry 7). This result was slightly inferior to the corresponding
R = H, Cl, Br, Me, Et
i
bimetallic catalyst 9d in both ee and yield (Table 1, entry 5).
Though there was not much direct information to prove the
inducement of axial chirality in biphenyl skeleton of bimetallic cat-
alyst 9, comparing our results with those of Mikami,14 it was sug-
gested that the R axial chirality of the biphenyl backbone was
L = PrOH
Scheme 5. The suggested inducement process of the complex 9 to form the R
configuration.
induced in the complex 9, which resulted in more catalytic activity
i
In conclusion, we have developed a new family of achiral
,3 ,5,5 -tetrasubstituted-2,2 ,6,6 -tetrahydroxy biphenyl ligand 4.
and higher enantioselectivity than (R)-BINOL-Ti(O Pr)
2
.
0
0
0
0
3
The R axial chirality inducement process in complex 9 could be
suggested as follows: R axial chirality in biphenyl skeleton was
The axial chirality of the ligand could be induced by the chelation
0
0
i
2
of 2,2 ,6,6 -tetrahydroxy groups with (R)-BINOL-Ti(O Pr) to form
induced by (R)-BINOL when achiral tetrahydroxy biphenyl 4 was
i
an axially chiral bimetallic titanium catalyst 9. And this novel
catalyst 9 exhibited excellent activity and enantioselectivity for
carbonyl-ene reaction of methylstyrene and ethyl glyoxylate
chelated with 1 equiv (R)-BINOL-Ti(O Pr)
2
to form monometallic
catalyst R,R-13 (Scheme 5), since 13 showed much better activity
i
and enantioselectivity compared with (R)-BINOL-Ti(O Pr)
1
2
(Table
i
0
0
1
4
compared with (R)-BINOL-Ti(O Pr) catalyst system. 3,3 ,5,5 -Tetra-
, entry 7). The similar phenomenon was also reported by Vallée
2
substituted groups showed remarkable effect on both enantio
and co-workers in the case of conformationally flexible biphenols,
0
0
selectivity and yield. With 9d prepared from 3,3 ,5,5 -tetra-
of which the axial chirality was induced by a chiral activator, (R)-
0
0
i
17
methyl-2,2 ,6,6 -tetrahydroxy biphenyl 4d as the catalyst, 97.6%
ee was obtained with 99% yield. Additionally, the bimetallic cata-
lyst 9 also showed better catalytic capability than the correspond-
ing monometallic one.
BINOL-Ti(O Pr)
(
5
2
.
R,R-13 was then chelated with another 1 equiv
to form bimetallic catalyst R,R,R-9 (Scheme
), which showed better catalytic behavior than the corresponding
i
R)-BINOL-Ti(O Pr)
2
monometallic one.
Acknowledgments
Table 1
This work was partially supported by the National Nature
Science Foundation of China, Nippon Chemical Industrial Co., Ltd,
and Instrumental Analysis Center of Shanghai Jiao Tong University.
a,15
The carbonyl-ene reaction catalyzed by 9 and 13d complex
Yieldb (%)
Eec (%)
Entry
R (cat.)
1d
2
3
4
5
—
74
99
99
89
99
91
90
90.0
93.1
91.3
94.1
97.6
96.8
96.1
References and notes
H (9a)
Cl (9b)
Br (9c)
CH
CH
CH
1.
For selected reviews on asymmetric catalysis, see: (a) Noyori, R. Asymmetric
Catalysis in Organic Synthesis; Wiley-Interscience: New York, 1994;
3
3
3
(9d)
CH (9e)
(13d)
(
b)Comprehensive Asymmetric Catalysis I-III; Jacobsen, E. N., Pfaltz, A.,
6
7
2
e
Yamamoto, H., Eds.; Springer: Berlin, 1999; (c) Ojima, I. Catalytic Asymmetric
Synthesis, 2nd ed.; Wiley-VCH: New York, 2000; (d) Berkessel, A.; Groeger, H.
Asymmetric Organocatalysis: From Biomimetic Concepts to Applications in
Asymmetric Synthesis; Wiley-VCH: Weinheim, 2005; (e) Hargaden, G. C.;
Guiry, P. J. Chem. Rev. 2009, 109, 2505.
a
b
c
The reaction was carried out with the molar ratio of 1/2/0.05 (10/11/9).
Isolated yield.
The ee was determined by HPLC on a chiral OJ column and absolute configu-
1
6
2. For selected reviews, see: (a) McCarthy, M.; Guiry, P. J. Tetrahedron 2001, 57,
809; (b) Shimizu, H.; Nagasaki, I.; Saito, T. Tetrahedron 2005, 61, 5405; (c) Li, Y.
ration was assigned to be R by comparing with the literature.
3
d
e
i
Using (R)-BINOL-Ti(O Pr)
The catalyst 13d was formed by mixing (R)-BINOL-Ti(O Pr)
molar ratio of 1:1, the reaction was carried out with the molar ratio of 1/2/0.1 (10/
1/13d).
2
as the catalyst.
M.; Kwong, F. Y.; Yu, W. Y.; Chan, A. S. C. Coord. Chem. Rev. 2007, 251, 2119; (d)
Ogasawara, M. Tetrahedron: Asymmetry 2009, 20, 259.
Mislow, K.; Glass, M. A. W.; Hopps, H. B.; Simon, E.; Wahl, G. H., Jr. J. Am. Chem.
Soc. 1964, 86, 1710.
i
2
and 4d with the
3.
1

F. Fang et al. / Tetrahedron Letters 50 (2009) 6672–6675
6675
4
.
.
(a) Gavrilova, A. L.; Bosnich, B. Chem. Rev. 2004, 104, 349; (b) Guo, H.; Wang, X.;
Ding, K. Tetrahedron Lett. 2004, 45, 2009.
(a) Zhang, Y. J.; Wang, F.; Zhang, W. J. Org. Chem. 2007, 72, 9208; (b) Wang, F.;
Yang, G.; Zhang, Y. J.; Zhang, W. Tetrahedron 2008, 64, 9413.
Yu, S. C.; Chie, Y. M.; Guan, Z. H.; Zhang, X. M. Org. Lett. 2008, 10, 3469.
12. Bimetallic catalyst 9 can be confirmed by Mass, for example 9d: ES+: m/z: 958
[M+23].
13. Yuan, Y.; Zhang, X.; Ding, K. Angew. Chem., Int. Ed. 2003, 42, 5478.
14. (a) Mikami, K.; Matsukawa, S. Nature 1997, 385, 613; (b) Mikami, K.;
Matsukawa, S.; Volk, T.; Terada, M. Angew. Chem., Int. Ed. 1997, 36, 2768.
5
6
7
.
.
0
0
0
0
1
3,3 ,5,5 -Tetrabromo-2,2 ,6,6 -tramethoxy biphenyl 5. Yield: 100%.
H
C
NMR
NMR
15. A general procedure for carbonyl-ene reaction: Under an atmosphere of argon,
13
i
(
400 MHz, CDCl
100 MHz, CDCl
3
):
d
7.84 (s, 2H, ArH), 3.64 (s, 12H, OCH
3
);
(R)-BINOL 14.3 mg (0.05 mmol) and Ti(O Pr)
4
14.8
l
l (0.05 mmol) were stirred
0 0
(
3
): d 156.37, 136.69, 125.91, 112.81, 61.18; HRMS calcd for
, 589.7585, found 589.7540.
in dry toluene 1 ml at rt for 30 min, and then to this mixture, 3,3 ,5,5 -
tetramethyl-2,2 ,6,6 -tetrahydroxy biphenyl 4d 6.8 mg (0.025 mmol) resolved
in 0.5 ml dry ether was added, and stirred for another 0.5 h at 60 °C. At 0 °C,
0
0
C
16
H
14Br
4
O
4
3,3 ,5,5 -Tetrabromo-2,2 ,6,6 -tetrahydroxy biphenyl 4c. Yield: 100%. 1H NMR
0
0
0
0
8
.
.
1
3
(
400 MHz, CDCl
DMSO-d 153.16, 134.59, 112.59, 101.43; HRMS calcd for
33.6959, found 533.6938.
3
): d 7.69 (s, 2H, ArH), 5.56 (s, 4H, OH); C NMR: (100 MHz,
a-methylstyrene 65 ll (0.5 mmol) and freshly distilled ethyl glyoxylate 117 ll
(1.0 mmol) were added and stirred at 0 °C for another 30 h. Pure product 12
was obtained by column chromatography over silica gel eluted with
6
)
d
C
12
H
6
Br
4
O
4
,
5
0
0
0
0
1
1
9
3,3 ,5,5 -Tetrachloromethyl-2,2 ,6,6 -tetramethoxy biphenyl 6. Yield: 94%. H NMR
petroleum/ethyl acetate (10:1). H NMR (400 MHz, CDCl
3
): d 7.44–7.28 (m,
), 4.30–4.24 (m, 1H, CHOH),
), 3.07 (dd, J = 4.5 Hz, 13.5 Hz, 1H, CCH CH), 2.84 (dd,
J = 8.1 Hz, 13.5 Hz, 1H, CCH CH), 2.73 (d, J = 6.0 Hz, 1H, OH), 1.24 (t, J = 7.2 Hz,
3H, CH ). Enantiomeric excesses were determined by HPLC using a Daicel
Chiralpak OJ column, eluent, hexane/ PrOH = 90/10, flow rate: 0.5 ml/min,
k = 254 nm, = 18.46 min (minor), 25.05 min (major), respectively, the
13
(
400 MHz, CDCl
NMR (100 MHz, CDCl
calcd for C20 22Cl
3
): d 7.57 (s, 2H, ArH), 4.67 (s, 8H, CH
2
), 3.61 (s, 12H, OCH
): d 157.87, 133.41, 127.58, 122.95, 61.88, 41.20; HRMS
3
);
C
5H, ArH), 5.44 (s, 1H, C@CH
4.15–4.00 (m, 2H, OCH
2 2
), 5.25 (s, 1H, C@CH
3
2
2
H
4
O
4
468.0243, found 468.0228.
2
0
0
00
1
1
1
0. 3,3 ,5,5 -Tetramethyl-2,2 ,6,6’-tetramethoxy biphenyl 7. Yield: 100%. H NMR
3
1
3
i
(
400 MHz, CDCl
NMR (100 MHz, CDCl
calcd for C20 330.1831, found 330.1798.
3
): d 7.03 (s, 2H, ArH), 3.49 (s, 4H, OCH
3
), 2.27 (s, 12H, CH
3
);
C
3
): d 156.23, 132.65, 126.04, 122.97, 60.17, 16.28; HRMS
t
R
H
26
O
4
absolute configuration of the homoallylic alcohol is R, based on literature data.
16. Wang, X.; Wang, X.; Guo, H.; Wang, Z.; Ding, K. Chem. Eur. J. 2005, 11, 4078.
17. Chavarot, M.; Byrne, J. J.; Chavant, P. Y.; Pardillos-Guindet, J.; Vallée, Y.
Tetrahedron: Asymmetry 1998, 9, 3889.
0
0
0
0
1
1. 3,3 ,5,5 -Tetramethyl-2,2 ,6,6 -tetrahydroxy biphenyl 4d. Yield: 100%. H NMR
13
(
400 MHz, CDCl
NMR (100 MHz, CDCl
for C16 , 274.1205, found 274.1200.
3
): d 7.04 (s, 2H, ArH), 4.71 (s, 4H, OH), 2.21 (s, 12H, CH
3
);
C
3
): d 156.81, 136.58, 119.99, 115.30, 21.56; HRMS calcd
18 4
H O