Heterogeneous Pd-catalyzed asymmetric allylic substitution using resin-supported Trost-type bisphosphane ligands

Article abstract of DOI:10.1002/1521-3773(20021018)41:20<3852::AID-ANIE3852>3.0.CO;2-I

Easy recovery and reutilization of the catalyst in consecutive reactions: These are the advantages offered by a new class of polymer-bound Trost-type ligands (see Figure; is a polystyrene-based resin or JandaJEL). A complex is formed with [{(η³-C₃H₅)PdCl}₂] that catalyzes asymmetric allylic substitutions with excellent activity and enantioselectivity (up to 99% ee).

Full text of DOI:10.1002/1521-3773(20021018)41:20<3852::AID-ANIE3852>3.0.CO;2-I

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readily recovered from the reaction mixture and offer the
possibility of reusing both components. Surprisingly, to the
best of our knowledge, there has been no report so far on the
use of a heterogeneous analogue of ligand 1 for asymmetric
allylic substitutions.[6]
Heterogeneous Pd-Catalyzed Asymmetric
Allylic Substitution Using Resin-Supported
Trost-Type Bisphosphane Ligands**
Choong Eui Song,* Jung Woon Yang, Eun Joo Roh,
Sang-gi Lee, Jou Hyeon Ahn, and Hogyu Han*
We present here the supported bisphosphane ligands 8a
and 8b, which are polymeric analogues of the Trost-type
ligand 1 and exhibit excellent activity and enantioselectivity
(up to 99% ee) in Pd-catalyzed desymmetrization reactions.
These ligands can be reused for consecutive reactions without
any further addition of a Pd source. The immobilized ligands 8
were designed with the following criteria: 1) The molecular
structure of the monomeric moiety should mimic precisely the
optimum structure of ligand 1; 2) the monomeric moiety
should be attached by a single flexible linkage to the polymer
support to minimize detrimental changes in the conforma-
tional preference of the reactant catalyst intermediates; and
3) the morphology of the resin should be such that no
limitation on mass transfer arises, with all active sites freely
accessible.
For economic, environmental, and social reasons, the trend
towards the application of optically pure compounds is
undoubtedly increasing. Among the various methods to
produce single enantiomers, asymmetric catalysis is one of
the most attractive from the atom-economic point of view
of.[1] Over the last thirty years, numerous catalytic reactions
ꢀ
ꢀ
ꢀ
allowing the enantioselective formation of C H, C C, C O,
ꢀ
C N, and other bonds have been discovered. A number of
homogeneous chiral catalysts have gained wide acceptance
owing to their efficiency and selectivity, and some of them are
even used on an industrial scale.[2] However, in spite of the
huge amount of work devoted to this subject in both academic
and industrial fields, the contribution of asymmetric catalysis
in the overall production of chiral chemicals is much lower
than originally expected. One of the major drawbacks of
homogeneous catalysis is the need for separating the rela-
tively expensive catalysts from the reaction mixture at the end
of the process. One of the most promising solutions to this
problem seems to be the anchoring of effective soluble
catalytic systems to an insoluble matrix, ideally without any
reduction of catalytic performance
The polymeric ligands 8 and their homogeneous analogue 7
were synthesized by the route depicted in Scheme 1. The
tBoc
tBoc
tBoc
N
N
N
a)
b)
N3
N3
H2N
NH2
MsO
OMs
2
3
4
with respect to the homogeneous
phase.[3]
c)
O
O
In our continuing effort to de-
velop efficient heterogeneous chi-
ral catalysts,[4] we became interest-
ed in the immobilization of Trost-
type bisphosphane ligands such as
1, which have proven to be ex-
NH HN
tBoc
H
N
N
PPh2 Ph2P
O
O
O
O
1
d)
NH HN
NH HN
PPh2 Ph2P
PPh2 Ph2P
tremely useful in palladium(0)-catalyzed asymmetric allylic
substitutions.[5] In spite of the versatility of this class of chiral
ligands, the catalytic system provides relatively lowturnover
numbers and frequencies, and both ligand 1 itself and
palladium are quite expensive. Thus, it would be highly
desirable to develop heterogeneous analogues that could be
6
5
P
e)
f)
CPh3
N
Ph
Ph
O
O
N
NH HN
[*] Dr. C. E. Song, E. J. Roh, Dr. S.-g. Lee
Life Sciences Division
O
O
PPh2 Ph2P
NH HN
PPh2 Ph2P
8
Korea Institute of Science and Technology
PO Box 131, Cheongryang, Seoul 130-650 (Korea)
Fax : (þ 82)2-958-5189
7
E-mail: s1673@kist.re.kr
Prof. H. Han, J. W. Yang
Department of Chemistry
Korea University
8a : Polystyrene-based resin (0.152 mmol g–1
8b : JandaJEL (0.174 mmol g–1
)
P
)
Seoul 136-701 (Korea)
Fax : (þ 82)2-3290-3121
E-mail: hogyuhan@korea.ac.kr
Scheme 1. Synthesis of the polymer-bound ligands 8. a) NaN3, DMF, 858C,
24 h, 78%; b) 10% Pd/C, H2 (50 psi), MeOH, 99%; c) DPPBA, DCC,
DMAP, CH2Cl2, RT, 24 h, 70%; d) BF3¥Et2O, CH2Cl2, 08C!RT, 1 h, 98%;
e) trityl chloride, Et3N, DMAP, CH2Cl2, RT, 1 h, 96%; f) polymer-bound
triphenylchloromethane (cross-linked with 1% DVB) for 8a or JandaJEL
trityl chloride for 8b, Et3N, DMAP, CH2Cl2, RT, 14 h. Boc ¼ tert-butoxy-
carbonyl, DCC ¼ dicyclohexylcarbodiimide, DMAP ¼ 4-dimethylamino-
pyridine, DPPBA ¼ 2-diphenylphosphanylbenzoic acid, DVB ¼ divinyl-
benzene, Ms ¼ methanesulfonyl.
Prof. J. H. Ahn
Department of Chemical Engineering
Gyeongsang National University
Chinju 660-701 (Korea)
[**] This research was supported by a grant (NRL-program: 2N22890)
from the Ministry of Science and Technology in Korea.
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Table 2. Results of the Pd-catalyzed intramolecular cyclization of biscarb-
catalytic reduction of N-tBoc-(3R,4R)-3,4-diazidopyrrolidine
(3), which was obtained by azide substitution of N-Boc-
(3S,4S)-3,4-bis(methanesulfonyloxy)pyrrolidine (2),[7] fol-
lowed by reaction of the resulting diaminopyrrolidine 4 with
2-diphenylphosphanylbenzoic acid (DPPBA) in the presence
of dicyclohexylcarbodiimide (DCC) afforded the monomeric
moiety 5. After deprotection[8] of the tBoc group of 5 with
BF3¥Et2O in CH2Cl2, the resulting monomeric ligand 6 was
allowed to react with polystyrene-based trityl chloride resin[9]
and JandaJEL trityl chloride[10] in the presence of triethyl-
amine in dichloromethane to give the pale yellowpolymeric
ligands 8a and 8b, respectively. The trityl chloride is relatively
inert to the formation of the phosphonium salt during the
anchoring of 6 to the polymer support. The polymeric chloride
moieties that remained were capped with methoxy groups[11]
(see the Experimental Section). Nitrogen analysis of 8a and
8b indicated that 0.152 and 0.174 mmolgꢀ1 of the monomeric
moiety 6 were incorporated, respectively. To compare the
catalytic efficiency in homogeneous and heterogeneous
reactions, the homogeneous analogue 7 was also prepared
by the reaction of 6 with trityl chloride.[12]
amate 10.[a]
chiral ligands
O
[{(η3-C3H5)PdCl}2]
O
O
O
O
NHTs
O
N
Et3N / THF / 0oC
TsHN
Ts
10
Entry
Ligand
Time [min]
Yield [%][b]
ee [%][c]
Config.
1
2
3
4[d]
5[d]
6[d]
7[d]
7
20
30
20
20
40
60
180
99
98
99
99
99
99
95
99
97.5
99
98.2
97.7
97.1
94.7
1S,4R
1S,4R
1S,4R
1S,4R
1S,4R
1S,4R
1S,4R
8a
8b
8b
8b
8b
8b
[a] All reactions were carried out on
a 0.2-mmol scale based on
biscarbamate 10 at 08C. The molar ratio of [{(h3-C3H5)PdCl}2]:ligand:10:
NEt3 was 0.025:0.075:1:1; Ts ¼ p-toluenesulfonyl. [b] Yields of isolated
product. [c] Determined by HPLC using Chiralpak AD column with
iPrOH/heptane (15/85), flowrate: 1.0 mLmin ꢀ1; elution times: 24.4 min
(1S,4R), 27.3 min (1R,4S). [d] The reaction was carried out with the 8b Pd
complex recovered from the previous run without further addition of [{(h3-
C3H5)PdCl}2].
The catalytic efficiency of the polymeric ligands 8 was
examined with the Pd-catalyzed desymmetrization[13] of cis-
1,4-bis(benzoyloxy)cyclopent-2-ene (9) with dimethylmalo-
nate nucleophile (Table 1) and the intramolecular cyclization
than Merrifield resin.[14] This characteristic of the JandaJEL
support is envisaged to give the bulky ligand greater degrees
of freedom and, as a result, to act more like a homogeneous
catalyst.
After the successful first run of the intramolecular cycliza-
tion of 10 (entry 3, Table 2), the reaction mixture was filtered
off under an argon atmosphere and the catalyst resin complex
was rinsed with dry THF (3 î 5 mL). The 31P NMR spectrum
of the recovered orange resin showed a signal at d ¼ þ
26.0 ppm (85% H3PO4 external reference). This remarkable
downfield shift indicates that the phosphanyl group of 8b in
the recovered resin is coordinated to palladium. Finally, the
recovered Pd complex of 8b was subjected to further catalytic
reactions without any further addition of a Pd source. The
recovered catalyst could be recycled with only a slight loss in
activity and enantioselectivity (from 99% ee in the first run to
94.7% ee in the fifth run; entries 3 7, Table 2). These results
demonstrate that in addition to highly facilitated workup
procedures, the JandaJEL-bound catalyst 8b offers the
advantage of easy recovery and reutilization in consecutive
heterogeneous asymmetric desymmetrization reactions.
In summary, we have prepared a promising class of
polymer-bound chiral ligands for heterogeneous asymmetric
allylic substitution reactions. In particular, the JandaJEL-
bound ligand 8b exhibited excellent activity and enantiose-
lectivity in Pd-catalyzed asymmetric desymmetrizations. To
the best of our knowledge, this is the first successful work on
heterogeneous asymmetric desymmetrization reactions in
which Trost-type ligands were used. Studies to optimize the
reaction conditions for continuous processing are currently in
progress.
Table 1. Results of the Pd-catalyzed desymmetrization of 9 with dimethyl-
malonate nucleophile.[a]
MeO2C
MeO2C
chiral ligands
3
Ph
O
O
Ph
O
Ph
[{(η -C3H5)PdCl}2]
O
O
CH2(CO2Me)2 / NaH
THF, 0 o
O
C
9
Entry
Ligand
Time
Yield [%][b]
ee [%][c]
Config.
1
2
3
7
8a
8b
1 h
15 h
30 min
98
73
98
98
84
96
1S,4R
1S,4R
1S,4R
[a] All reactions were carried out on a 0.2-mmol scale based on substrate 9
at 08C. The molar ratio of [{(h3-C3H5)PdCl}2]:ligand:9:NaH(95%):dime-
thylmalonate was 0.025:0.15:1:1.8:1.5. [b] Yields of isolated product.
[c] Determined by HPLC using Chiralcel OJ column with iPrOH/hexane
(15/85), flowrate: 1.0 mLmin ꢀ1; elution times: 15.8 min (1S,4R), 21.5 min
(1R,4S).
of biscarbamate 10 (Table 2). The catalytic activity and
enantioselectivity of the monomeric analogue 7 was first
investigated as a control experiment. We were pleased to find
that this ligand showed high activity and enantioselectivity
(up to 99% ee) in the Pd-catalyzed desymmetrization reac-
tions of 9 and 10 (entry 1, Tables 1 and 2). This result indicates
that the homochiral pyrrolidine diamine moiety is an appro-
priate chiral scaffold for the catalyst.
With these results in hand, we turned to studying polymer-
bound 8a and 8b. The activity and enantioselectivity of the
polystyrene-based catalyst 8a (entry 2, Tables 1 and 2) were
slightly lower than those obtained with 7. However, the
JandaJEL-based catalyst 8b (entry 3, Tables 1 and 2) was
nearly as effective (up to 99% ee) as 7. The JandaJEL resin is a
polystyrene resin containing flexible tetrahydrofuran-derived
cross-linkers, and is therefore reported to swell much better
Experimental Section
8b: Compound 6 (288.7 mg, 0.426 mmol) and Et3N (89 mL, 0.639 mmol)
were added to a suspension of polymer-bound triphenylchloromethane
(JandaJEL; 2.0 g, 1.42 mmol) in CH2Cl2 (50 mL), and the mixture was
stirred at ambient temperature for 14h under a nitrogen atmosphere. The
resin was filtered and washed with CH2Cl2 (160 mL), water (150 mL), and
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methanol (200 mL) and then dried under vacuum. To cap the unchanged
chloride moieties with methoxy groups, the resin was stirred for 15 min in
CH2Cl2/methanol (1/1, v/v; 15 mL) containing an excess of Et3N (383 mL,
2.75 mmol). The resin was filtered and washed with CH2Cl2 (50 mL), water
(150 mL), and methanol (200 mL). To remove any traces of unchanged
chiral monomer 6 in the resin, 8b was then continuously extracted in a
Soxhlet device with THF for 24h and dried under vacuum. Solid-state 31P
NMR (85% H3PO4 external reference): d ¼ ꢀ11.6 ppm (brs).
Noncovalent Chemistry of Nitrous Oxide:
Interactions with Secondary cis Amides in
Solution**
Grigory V. Zyryanov, Erin M. Hampe, and
Dmitry M. Rudkevich*
The environmental impact of nitrous oxide (N2O) is
enormous. As one of the most abundant components of the
atmosphere, N2O plays a critical role in the destruction of the
ozone layer and contributes to the greenhouse effect.[1]
Emission of N2O into the atmosphere has already reached
13 million tons and is constantly growing. The widespread use
of nitrogen-containing fertilizers and the industrial manufac-
ture of nylon are critical contributors to this amount. The
major natural suppliers of N2O are enzyme-supported nitri-
fication/denitrification processes in soils in which this gas is
the key intermediate.[2] N2O is also involved in a number of
biochemical processes, especially related to anesthesia.[3]
Together with O2 and CO, N2O belongs to the family of
blood gases.
The chemistry of N2O is limited, although it is considered to
be a reliable and nontoxic source of oxygen for catalysis.[4] It is
commonly known as a noncoordinating gas and as a very poor
ligand. Although several metal complexes react with N2O,
[Ru(NH3)5(N2O)]2þ is the only characterized complex to
date.[5]
The rules governing reversible interactions between N2O
and various receptor sites, which usually precede the covalent
fixation and are also responsible for the biochemical action,
are still poorly understood. We report herein the previously
unnoticed noncovalent interactions between secondary
amides and N2O in apolar solutions. N2O frequently circulates
in biological fluids,[2,3] and its rather weak dipole dipole
interactions with hydrophobic fragments of proteins has been
noticed.[6] At the same time, the possibility of its involvement
in hydrogen bonding with proteins and enzymes has been
routinely ignored.
Hydrogen bonding is one of the most important forces in
Nature and is responsible for self-assembly and enzyme
selectivity.[7] In chemistry, it has been used in the design of
effective receptors for polar neutral molecules and anions in
the gas phase, in solution, and in the solid state.[8] Molecules of
gases are known to form hydrogen bonds in the gas phase.
Among the typical examples are the adducts of acidic HF,
HCl, HBr, and HCN with N2, CO, CO2, and OCS,[9] and weak
PhOH¥¥¥Ar (N2, CO) molecular clusters.[10] At the same time,
Received: April 15, 2002 [Z19097]
[1] a) Comprehensive Asymmetric Catalysis, Vol. I III (Eds.: E. N. Jacob-
sen, A. Pfaltz, H. Yamamoto), Springer, Berlin, 1999; b) Catalytic
Asymmetric Synthesis (Ed.: I. Ojima), Wiley-VCH, NewYork, 2000.
[2] a) Chirality in Industry, Vol. I (Eds.: A. N. Collins, G. N. Sheldrake, J.
Crosby), Wiley, NewYork, 1992; b) Chirality in Industry, Vol. II(Eds.:
A. N. Collins, G. N. Sheldrake, J. Crosby), Wiley, NewYork, 1996.
[3] B. Pugin, H.-U. Blaser in Comprehensive Asymmetric Catalysis, Vol. 3
(Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer, Berlin,
1999, p. 1367.
[4] a) C. E. Song, J. W. Yang, H.-J. Ha, Tetrahedron: Asymmetry 1997, 8,
841; b) C. E. Song, C. R. Oh, S. W. Lee, S.-g. Lee, L. Canali, D. C.
Sherrington, Chem. Commun. 1998, 2435; c) C. E. Song, E. J. Roh,
B. M. Yu, D. Y. Chi, S. C. Kim, K.-J. Lee, Chem. Commun. 2000, 615.
[5] Reviews: a) B. M. Trost, D. L. Van Vranken, Chem. Rev. 1996, 96, 395;
b) B. M. Trost, C. Lee in Catalytic Asymmetric Synthesis (Ed.: I.
Ojima), Wiley-VCH, NewYork, 2000, p. 593; c) A. Pfaltz, M. Lautens
in Comprehensive Asymmetric Catalysis, Vol. 2 (Eds.: E. N. Jacobsen,
A. Pfaltz, H. Yamamoto), Springer, Berlin, 1999, p. 833.
[6] Heterogeneous versions of other types of chiral ligands for asym-
metric allylic substitutions have recently been reported: a) Y. Uozumi,
K. Shibatomi, J. Am. Chem. Soc. 2001, 123, 2919; b) K. Hallman, E.
Macedo, K. Nordstrˆm, C. Moberg, Tetrahedron: Asymmetry 1999, 10,
4037; c) Y. Uozumi, H. Danjo, T. Hayashi, Tetrahedron Lett. 1998, 39,
8303; d) M. S. Anson, A. R. Mirza, L. Tonks, J. M. J. Williams,
Tetrahedron Lett. 1999, 40, 7147; e) B. F. G. Johnson, S. A. Raynor,
D. S. Shephard, T. Mashmeyer, J. M. Thomas, G. Sankar, S. Bromley,
R. Oldroyd, L. Gladden, M. D. Mantle, Chem. Commun. 1999, 1167.
[7] U. Nagel, Angew. Chem. 1984, 96, 425; Angew. Chem. Int. Ed. Engl.
1984, 23, 435.
[8] R. G. Hiskey, L. M. Beacham, V. G. Matl, J. N. Smith, E. B. Williams,
A. M. Thomas, E. T. Wolters, J. Org. Chem. 1971, 36, 488.
[9] Polymer-bound triphenylchloromethane (cross-linked with 1% DVB;
100 200 mesh; ca. 1.1 mmol Cl per gram of resin) was purchased from
Fluka.
[10] R. Manzotti, T. S. Reger, K. D. Janda, Tetrahedron Lett. 2000, 41, 8417.
[11] K. Barlos, O. Chatzi, D. Gatos, G. Stavropoulos, Int. J. Pept. Protein
Res. 1991, 37, 513.
[12] Physical data for 7: 1H NMR (300 MHz, CDCl3): d ¼ 2.15 2.21 (m,
1H), 2.75 2.81 (m, 1H), 3.78 3.83 (m, 1H), 6.24 (d, J ¼ 4.4 Hz, 1H),
6.89 6.93 (m, 1H), 7.16 7.36 (m, 18H), 7.43 (d, J ¼ 7.5 Hz, 3H), 7.54
7.58 ppm (m, 1H); 13C NMR (75.5 MHz, CDCl3): d ¼ 51.93, 55.50,
74.89, 126.73, 128.06, 128.35, 128. 41, 128.97, 129.00, 129.06, 129.09,
129.19, 129.27, 129.73, 130.66, 134.17, 134.25, 134.44, 134.51, 136.49,
136.77, 137.50, 137.60, 137.65, 137.75, 141.07, 141.40, 142.57, 169.76 ppm;
31P NMR (121 MHz, CDCl3, 85% H3PO4 as external reference): d ¼
ꢀ9.6 ppm.
[13] B. M. Trost, D. L. Van Vranken, C. Bingel, J. Am. Chem. Soc. 1992,
114, 9327.
[14] P. H. Toy, K. D. Janda, Tetrahedron Lett. 1999, 40, 6329.
[*] Prof. Dr. D. M. Rudkevich, Dr. G. V. Zyryanov, E. M. Hampe
Department of Chemistry and Biochemistry
University of Texas at Arlington
P. O. Box 19065, Arlington, TX 76019 (USA)
Fax : (þ 1)817-272-3808
E-mail: rudkevich@uta.edu
[**] We are grateful to the University of Texas at Arlington for financial
support. Prof. Dr. H. V. R. Dias and D. Jayasundara are acknowledged
for advice and experimental assistance, respectively. We thank Dr. A.
Shivanyuk for the expert assistance with calculations, and Prof. Dr. H.
Kessler for providing us with the reprints of his early work.
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Angew. Chem. Int. Ed. 2002, 41, No. 20