The first optically active BINOL-BINAP copolymer catalyst: Highly stereoselective tandem asymmetric reactions [7]

Full text of DOI:10.1021/ja000778k

6500
J. Am. Chem. Soc. 2000, 122, 6500-6501
The First Optically Active BINOL-BINAP
Copolymer Catalyst: Highly Stereoselective Tandem
Asymmetric Reactions
Hong-Bin Yu, Qiao-Sheng Hu, and Lin Pu*
Department of Chemistry, UniVersity of Virginia
CharlottesVille, Virginia 22901
ReceiVed March 3, 2000
Optically active 1,1′-bi-2-naphthol [BINOL, (R)-1] and 2,2′-
bis(diphenylphosphino)-1,1′-binaphthyl [BINAP, (R)-2] represent
two most important classes of chiral biaryl ligands and have found
very extensive applications in asymmetric catalysis.1 BINOL
ligands contain hard oxygen atoms and are used to coordinate
with hard metal centers such as Al(III), Ti(IV), Zn(II), and Ln-
-9
Scheme 1. Synthesis of the First BINOL-BINAP Copolymer
(III) to generate highly enantioselective Lewis acid catalysts for
many asymmetric organic transformations such as Diels-Alder
reactions, Michael additions, ene reactions, and organometal
additions to carbonyls.5 BINAP ligands contain soft phosphorus
atoms and are used to coordinate with soft late transition metals
such as Rh and Ru to carry out asymmetric hydrogenations, olefin
isomerizations and others.8 The distinctively different coordi-
native ability of BINOL versus BINAP provides an excellent
opportunity to design novel multifunctional catalysts for tandem
asymmetric reactions by joining these two types of ligands.
-7
,9
Recently, we have discovered that an optically active BINOL
polymer (R)-3 can catalyze highly enantioselective diethylzinc
be dissolved in common organic solvents such as CH
2
Cl
2
, THF,
toluene, and DMF. Its molecular weight is M
Mn ) 7500 (PDI ) 1.55) as measured by gel permeation
chromatography relative to polystyrene standards. The specific
w
) 11 600 and
addition to a broad range of aldehydes including aryl, alkyl, and
R,â-unsaturated aldehydes.10 We have also found that an optically
2 6 6 2
active BINAP polymer (R)-4 after treated with [RuCl (C H )]
optical rotation of (R,R)-8 is [R]
D
2 2
) -75 (c ) 0.14, CH Cl ).
and (R,R)-1,2-diphenylethylenediamine (DPEN) can catalyze
1
11
The H NMR spectrum of this polymer is well resolved, indicating
a well-defined structure. The 31P NMR spectrum of the polymer
displays a predominate singlet at δ -14.77, consistent with the
BINAP units.11 Polymer (R,R)-8 was then converted to a
highly enantioselective hydrogenation of ketones. These dis-
coveries demonstrate that the rigid and sterically regular polybi-
naphthyl structure can preserve the stereoselectivity of monomer
catalysts. This has encouraged us to synthesize the copolymers
of BINOL and BINAP ligands for tandem asymmetric reactions.
Herein, our synthesis and study of the first optically active BINOL
and BINAP copolymer ligand is communicated.
polymeric ruthenium(II) complex 9 by reacting with [RuCl
)]
and (R,R)-DPEN. The 31P NMR spectrum of polymer 9
shows a singlet at δ 46.33, the same as the monomeric BINAP
2
-
(C
H
6 6
2
1
3
ruthenium complex reported by Noyori and co-workers.
We have used a triphenylene dibromide linker molecule 5 to
copolymerize with the optically active monomers (R)-6 and (R)-7
in a 2:1:1 ratio. After several steps including the Suzuki coupling,
reduction of the phosphoryl groups and hydrolysis of the BINOL-
protecting groups, a copolymer (R,R)-8 was obtained (see Scheme
1
and details in the Supporting Information). In this polymer, the
BINOL and BINAP units are expected to be distributed randomly
along the polymer chain. This polymer is a yellow solid and can
(
1) Whitesell, J. K. Chem. ReV. 1989, 89, 1581.
(
2) Rosini, C.; Franzini, L.; Raffaelli, A.; Salvadori, P. Synthesis 1992,
5
03.
(
3) Bringmann, G.; Walter, R.; Weirich, R. Angew. Chem., Int. Ed. Engl.
1
990, 29, 977.
(
4) Pu, L. Chem. ReV. 1998, 98, 2405.
(
5) Maruoka, K.; Yamamoto, H. In Catalytic Asymmetric Synthesis; Ojima,
I., Ed.; VCH: New York, 1993; p 413.
We have studied the use of the poly(BINOL-BINAP)-
ruthenium complex 9 in a tandem catalytic asymmetric diethylzinc
(
6) Shibasaki, M.; Sasai, H.; Arai, T. Angew. Chem., Int. Ed. Engl. 1997,
3
6, 1236.
(
7) Keck, G. E.; Tarbet, K. H.; Geraci, L. S. J. Am. Chem. Soc. 1993, 115,
8
467.
(12) Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J. Am.
Chem. Soc. 1995, 117, 2675.
(13) Doucet, H.; Ohkuma, T.; Murata, K.; Yokozawa, T.; Kozawa, M.;
Katayama, E.; England, A. F.; Ikariya, T.; Noyori, R. Angew. Chem., Int. Ed.
1998, 37, 1703.
(
(
(
(
8) Noyori, R. Acc. Chem. Res. 1990, 23, 345.
9) Noyori, R. Tetrahedron 1994, 50, 4259.
10) Huang, W.-S.; Hu, Q.-S.; Pu, L. J. Org. Chem. 1999, 64, 7940.
11) Yu, H.-B.; Hu, Q.-S.; Pu, L. Tetrahedron Lett. 2000, 41, 1681.
1
0.1021/ja000778k CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/23/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 27, 2000 6501
Scheme 2. Tandem Asymmetric Reaction Involving
Diethylzinc Addition and Hydrogenation
pressure reactor and was degassed by two freeze-pump-thaw
cycles. Hydrogen pressure (150 psi) was applied to the reactor
which was stirred at room temperature for 2 d. After release of
the hydrogen pressure, CH
organic solution was washed with 1 N HCl (5 mL × 2) and brine
5 mL × 3). After concentration under vacuum, polymer complex
was recovered from the organic solution by precipitation with
2 2
Cl (10 mL) was added, and the
(
9
MeOH. Removal of the solvents from the organic solution
followed by purification with column chromatography on silica
gel (hexane:EtOAc ) 3:1) gave 11 in 99% yield. The ee (92%)
and de (86%) of the product were determined by GC-chiral
column after converted to the corresponding diacetate.
In addition to the uses in the tandem asymmetric reactions,
the bifunctional poly(BINOL-BINAP) catalyst can be also used
as either BINOL or BINAP catalyst for individual asymmetric
reactions. For example, we have used polymer 9 to catalyze the
asymmetric hydrogenation of acetophenone to (S)-1-phenyletha-
nol. We found that polymer 9 not only showed high enantiose-
lectivity similar to the monomeric BINAP-Ru catalysts, but also
gave high catalytic turn-overs. In the presence of polymer 9 with
a BINAP unit to substrate ratio of 1:4900, the hydrogenation was
Table 1. Tandem Asymmetric Reactions of Acetyl Benzaldehydes
in the Presence of the Multifunctional Chiral Polymer Catalyst
solvent
Et
2
Zn
H
2
conv.
(%) (%)
ee
de
(%)
a
b,c
b,d
entry
1
substrate
p-acetyl
benzaldehyde
p-acetyl
benzaldehyde
p-acetyl
benzaldehyde
m-acetyl
addition addition
toluene iPrOH
>99% 92
86
2
toluene toluene + >99% 94
87
78
75
i
e
PrOH
3f
4
toluene PrOH
i
>99% 93
>99% 94
toluene iPrOH
completed with >99% conversion and 84% ee. The reaction was
benzaldehyde
i
conducted under H
2
(175 psi) in toluene/ PrOH (1:1) in the
a
1
b
t
Determined by H NMR. Determined by GC-chiral â-Dex 120
presence of BuOK at room temperature. Polymer 9 catalyzed
the diethylzinc addition to 10 to generate (R)-1-(p-acetylphenyl)-
propanol with 95% ee and complete conversion at 0 °C in 5.5 h
at a BINOL unit:substrate ratio of 1:50.
c
column after converted to the diacetate. For the diethylzinc addition.
d
For the hydrogenation. e Toluene: PrOH ) 1:1. Toluene in the ZnEt
i
2
f
addition step is not removed. The recovered catalyst was used.
In summary, the first optically active BINOL-BINAP copoly-
mer catalyst has been designed and synthesized. This novel
multifunctional polymer catalyst has shown excellent stereose-
lectivity in tandem asymmetric reactions involving diethylzinc
addition to aldehydes and hydrogenation of ketones. It demon-
strates that the rigid polybinaphthyl structure not only can preserve
the catalytic properties of a monomer catalyst but can also allow
distinctively different catalytic sites to function independently in
the polymer chain to conduct different asymmetric reactions. The
use of the copolymer catalyst rather than a mixture of monomer
catalysts greatly simplifies the recovery of the catalysts as well
as the purification of the products in the tandem asymmetric
reaction. In addition, the rigid polymer structure prevents possible
interferences between the monomer catalysts. Using copolymer
catalysts is also potentially more advantageous than using polymer
mixtures since it can avoid the inhomogeneity problems such as
phase-separation and solubility difference associated with the use
and recovery of the polymer mixtures. Besides the uses in tandem
asymmetric catalysis, the distinctive catalytic functions of the
BINOL and BINAP units also allows the copolymer to be used
in individual reactions that require either BINOL- or BINAP-
addition and asymmetric hydrogenation of p-acetylbenzaldehyde
(
10)1 to generate chiral diol 11 (Scheme 2). The experimental
results are summarized in Table 1. In the presence of 4 mol %
based on the repeating unit of the copolymer) of the BINOL-
4a,b
(
BINAP copolymer catalyst 9, the two asymmetric reactions
proceeded efficiently to generate chiral diol 11. We found that
the ee for the diethylzinc addition was 92%, and the de for the
hydrogenation step was 86% (entry 1, Table 1). The configurations
for the two chiral centers in 11 are assigned to be R and S as
shown in Scheme 2 on the basis of the previous studies on the
polymer and monomer catalysts.1
0-13,15
The stereoselectivities of
the copolymer catalyst are similar to those of the corresponding
monomer catalysts when used independently.1
2,13,15
We have also
carried out the tandem asymmetric diethylzinc addition and
hydrogenation of m-acetylbenzaldehyde1
4c,d
using copolymer
catalyst 9 and have observed good stereoselectivity for the
formation of chiral diol 12 (entry 4, Table 1). The copolymer
catalyst can be easily recovered by simple precipitation and
filtration. The recovered copolymer showed almost the same
enantioselectivity for the diethylzinc addition step and a slightly
lower diastereoselectivity for the hydrogenation step (entry 3,
Table 1).
based catalysts. Therefore, the work reported here points a new
16,17
direction to design chiral polymer catalysts
synthesis.
for asymmetric
A typical experimental procedure for the tandem asymmetric
reactions is given here. Under nitrogen, Et Zn (0.049 g, 0.40
2
mmol) was added to a toluene (2 mL) solution of polymer 9 (0.020
g, 0.0080 mmol, based on the polymer repeating unit) in a 10
mL flask. The mixture was stirred at room temperature for 15
min, and then 10 (0.030 g, 0.20 mmol) was added. The reaction
mixture was stirred at 0 °C for 5 h and was quenched by addition
Acknowledgment. This research was supported by the department
of chemistry at University of Virginia. We also thank the partial support
of this research by the U.S. National Science Foundation (DMR-9529805)
and the National Institute of Health (1R01GM58454).
Supporting Information Available: Detailed experimental proce-
dures and characterizations involving all of the monomers and polymers
and the GC analysis results of the chiral alcohol products (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
i
of PrOH (0.5 mL). After removal of the solvent under vacuum,
t
i
BuOK (0.010 g, 0.090 mmol) and PrOH (1.5 mL) were added.
The reaction flask was then placed inside a 125 mL stainless steel
(
14) (a) Tateiwa, J.-i.; Horiuchi, H.; Uemura, S. J. Org. Chem. 1995, 60,
JA000778K
4
039. (b) Milstein, D.; Stille, J. K. J. Org. Chem. 1979, 44, 1613. (c)
Karmanova, I. B.; Vol’eknsktein, Y. B.; Belen’kil, L. I. Chem. Heterocycl.
Compd. 1973, 9, 451. (d) Bromilow, J.; Bronlee, R. T.; Craik, D. J.; Sadek,
M. Magn. Reson. Chem. 1986, 24, 862.
(16) Itsuno, S. In Polymeric Materials Encyclopedia; Synthesis, Properties
and Applications; Salamone, J. C., Ed.; CRC Press: Boca Raton, FL, 1996;
Vol. 10, p 8078.
(15) Huang, W.-S.; Hu, Q.-S.; Pu, L. J. Org. Chem. 1998, 63, 1364.
(17) Pu, L. Chem. Eur. J. 1999, 5, 2227.