Novel 1,4-diphosphanes with imidazolidin-2-one Backbones as chiral ligands: Highly enantioselective Rh-catalyzed hydrogenation of enamides

Article abstract of DOI:10.1002/1521-3773(20020301)41:5<847::AID-ANIE847>3.0.CO;2-F

Appropriate gauche steric interactions between the N-substituents and the phosphanylmethyl groups (see picture, top right) in the novel 1,4-diphosphane ligands 1 having an imidazolidin-2-one backbone affect the conformational flexibility of the seven-memb

Full text of DOI:10.1002/1521-3773(20020301)41:5<847::AID-ANIE847>3.0.CO;2-F

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selectivity.[8] Here we report a new type of 1,4-diphosphane
ligands with an imidazolidin-2-one backbone, namely, (4S,5S)-
Novel 1,4-Diphosphanes with Imidazolidin-2-
one Backbones as Chiral Ligands: Highly
Enantioselective Rh-Catalyzed Hydrogenation
of Enamides**
4,5-bis(diphenylphosphanylmethyl)imidazolidin-2-ones
1
(bdpmi, Figure 2), which showed excellent enantioselectiv-
ities in Rh-catalyzed hydrogenation of a-arylenamides, a
reaction that has attracted considerable attention recently.[9]
Sang-gi Lee,* Yong Jian Zhang, Choong Eui Song,
Jae Kyun Lee, and Jung Hoon Choi
Transition metal catalyzed asymmetric hydrogenation is
one of the most powerful methods for the synthesis of
optically active compounds, and the development of new
chiral phosphanes plays a crucial role in this area.[1, 2] Since
Kagan and Dang developed the first C2-symmetric 1,4-
diphosphane ligand (diop) in the early 1970s,[3] many diop
analogues (A and B in Figure 1) have been synthesized and
Figure 2. (S,S)-bdpmi ligands 1 and the Newman projection showing
possible gauche interactions.
The design of the bdpmi ligands 1 was based on the
following hypothesis: the consecutive gauche steric interac-
tions between the N-substituents and phosphanylmethyl
groups, as revealed in Newman projections (Figure 2), may
influence the conformational flexibility of the seven-mem-
bered metal-chelate ring, and the enantioselectivity could
therefore be strongly dependent on the steric nature of the R
groups.
To test this hypothesis, a number of substituents R with
different bulkiness were introduced on the nitrogen atom of
imidazolidin-2-one (Scheme 1). Straightforward conversion
of l-tartaric acid to the C2-symmetric vicinal diamine 2[10] and
subsequent reaction of 2 with carbonyldiimidazole (CDI) led
to the key intermediate 3 in 40% overall yield. Deprotection
Figure 1. Various types of 1,4-diphosphanes forming seven-membered
metal chelate rings.
applied in various asymmetric catalytic reactions.[4] However,
the enantioselectivities obtained with these diop-type 1,4-
diphosphane ligands are not always sufficiently high. It is
generally believed that the low enantioselectivities with diop-
type 1,4-diphosphanes are largely due to the formation of
comformationally flexible seven-membered metal-chelate
rings. Thus, transfer of backbone chirality through a methyl-
ene group to the phenyl group on the phosphane may not be
efficient.[5] Only a few diphosphane ligands forming seven-
membered metal chelates (e.g., axially chiral binap[6] and
bicp[7]) achieved high enantioselectivities. More recently,
ligands C have been introduced in which the configurations
of the stereogenic centers are crucial to obtain high enantio-
O
O
H2N
BnO
NH2
R
R
a
N
N
b,d–f
HN
NH
OBn
PPh2
1b–1g
Ph2P
OBn
BnO
d–f
3
2
c–f
O
O
Ph
Ph
[*] Dr. S.-g. Lee, Dr. C. E. Song, J. K. Lee
Life Sciences Division
HN
NH
N
N
Korea Institute of Science and Technology
P.O. Box 131, Cheongryang, Seoul 130-650 (Korea)
Fax : (‡82)2-958-5189
PPh2
Ph2P
Ph2P
PPh2
1a
1h
E-mail: sanggi@kist.re.kr
Scheme 1. a) CDI (1.2equiv), CH 2Cl2, reflux, 4 h, 94%; b) NaH, RBr,
THF, reflux; R ˆ H, Me: 35%; Me, Me: 89%; Et, Et: 91%; iPr, iPr: 16%;
iBu, iBu: 43%; Bn, Bn: 90%; c) PhBr, tBuONa, Pd-dppf, toluene, 96%;
d) H2/Pd C, MeOH, RT, 82 99% or for R ˆ Bn, Pd(OH)2/C, cyclo-
hexene, MeOH/EtOAc (1:1), reflux, 81%; e) TsCl (2.2 equiv), pyridine,
71 86% or for R ˆ Bn: MsCl (2.2 equiv), Et3N, CH2Cl2, 74%; f) KPPh2,
CH2Cl2, RT, R ˆ H, H: 76%; H, Me: 73%; Me, Me: 70%; Et, Et: 67%; iPr,
iPr: 74%; iBu, iBu: 77%; Bn, Bn: 74%; Ph, Ph: 70%. dppf ˆ 1,1×-
bis(diphenylphosphino)ferrocene.
Y. J. Zhang, Prof. J. H. Choi
Department of Chemistry
Hanyang University
Seoul 133-791 (Korea)
[**] This work was supported by the Ministry of Science and Technology
(National Research Laboratory Program).
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
Angew. Chem. Int. Ed. 2002, 41, No. 5
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847

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of the O-benzyl groups (after N-alkylation for 1b 1g) and
tosylation (mesylation for 1g) followed by reaction with
potassium diphenylphosphide afforded ligands 1a 1g. The
N-phenyl group of 1h was introduced by using the Hartwig
Buchwald arylamination method.[11]
N-Acetylphenylethenamine (4a) was used as model sub-
strate for hydrogenation. All reactions were carried out at
208C under 1 atm of H2 and with an Rh:ligand ratio of 1:1.2
(Table 1).[12] Although a standard reaction time of 12h was
O
O
R
R
N
N
R
R
N
N
Me
Me
Me
Me
a, b) DABCO
P
OMe
MeO
P
2
2
TsO
OTs
Me
BH3
: R = H, H (78%)
: R = Me, Me (74%)
1i
1j
a)
HP
OMe
2
/ nBuLi/THF
1k: R = Bn, Bn (64%)
Me
Table 1. Rh-catalyzed asymmetric hydrogenation of N-acetyl phenyle-
thenamine 4a with 1a 1h as chiral ligands.[a]
H2 (1 atm )
H2 (1 atm )
100% conv. 40.9% ee with 1i
100% conv. 86.5% ee with 1j
100% conv. 71.7% ee with 1k
1 (1.2 mol %)
1 (1.2 mol %)
Ph
NHAc
Ph
NHAc
[Rh(cod)2]BF4
(1 mol %)
CH2Cl2, 12 h
[Rh(cod)2]BF4
(1 mol %)
CH2Cl2, 12 h
Ph
NHAc
Ph
NHAc
4a
5a
4a
Ligand
5a
Scheme 2. Synthesis of ligands 1i k and Rh-catalyzed hydrogenation of
enamide 4a with 1i 1k as ligands. DABCO ˆ 1,4-diaza[2.2.2]bicyclooc-
tane.
Entry
Conv. [%][b]
ee [%][c]
Config.[d]
1
2
3
4
5
6
7
8
9
(S,S)-diop
100
100
100
100
100
100
100
100
100
60.2
86.4
94.0
98.5
97.3
95.7
97.2
96.2
94.6
R
R
R
R
R
R
R
R
R
1a
1b
1c
1d
1e
1 f
1g
1h
The catalytic hydrogenation can be applied successfully to a
series of a-arylenamides 4b 4g to give chiral amine deriv-
atives 5b 5g with Me2bdpmi 1c (Table 2). In all cases, the
N,N-dimethylated ligand 1c exhibited excellent enantioselec-
tivity. The electronic nature of the para substituents in a-
phenylenamides has an effect on the enantioselectivity.
Enamides with electron-donating substituents (4b and 4e,
entries 1 and 4 in Table 2) give higher enantioselectivity than
those with electron-withdrawing substituents (4c and 4d,
entries 2and 3). Remarkably, the mixtures of E- and Z-
enamides 4g 4k (E/Z ˆ 1:2.0 2.5) were also reduced with
very high enantioselectivities (>99.0% ee, entries 6 10). It is
noteworthy that the ee values of 97.8 99.0% obtained with
bdpmi ligand 1c are higher than or comparable to those
obtained with other families of efficient chiral diphosphane
ligands.[8, 9]
[a] The reaction conditions were [Rh(cod)2]BF4:ligand:substrate
0.01:0.012:1, H2 pressure 1 atm, reaction time 12h, solvent CH 2Cl2, room
temperature. [b] Determined by 1H NMR and GC analysis. [c] Determined
by chiral GC on a CP-Chirasil-Dex CB column. [d] Determined by
comparing the sign of the optical rotation with that reported in ref. [9b].
chosen, most reactions were complete within 4 h. With 1a,
which does not have N-substitutents, 4a was hydrogenated to
5a with 86.4% ee (entry 2). Under the same conditions,
60.2% ee was obtained with diop (entry 1). Introducing one
N-methyl group (1b) increased the enantioselectivity to
94.0% ee (entry 3). The enantioselectivity was further in-
creased with N,N-dimethylated ligand 1c to 98.5% ee (en-
try 4). Comparison of the sense of asymmetric induction
imparted by diop, 1a, 1b,and 1c suggested that the steric
interactions between the N-substituents and the phosphanyl-
methyl group is one of the key elements that controls
enantioselectivity. However, N-substituents larger than meth-
yl resulted in slightly lower enantioselectivities (entries 5 9),
that is the ee values decreased with increasing A values of the
N-substituents.[13]
Significantly lower ee values were obtained with 1i 1k,
synthesized by reaction of the tosylated intermediates for
ligands 1a and 1c (mesylated for 1g) with lithium bis(3,5-
dimethyl-4-methoxyphenyl)phosphide borane complex.[14]
The NH ligand 1i hydrogenated 4a with only 40.9% ee,
whereas the enantioselectivity with the N,N'-dimethylated
ligand 1j increased to 86.5% ee (Scheme 2). The ligands 1i
1k possessing electron richer and bulkier phosphane groups
uniformly give lower ee values than the corresponding 1a, 1c,
and 1g, and this indicates that steric effects alone may not be
responsible for controlling enantioselectivity. However, the
reason for the striking deterioration in enantioselectivity with
1i 1k is not clear at present.
Table 2. Rh-catalyzed asymmetric hydrogenation of various N-acetyl a-
arylenamides with 1c as chiral ligand.[a]
R1
R1
H2 (1 atm )
1c (1.2 mol %)
[Rh(cod)2]BF4
(1 mol%)
CH2Cl2, 12 h
Ar
NHAc
Ar
NHAc
4
5
Entry
4
Ar, R1
Conv. [%][b]
ee [%][c]
Config.[d]
1
2
3
4
5
6
7
8
9
4b
4c
4d
4e
4 f
4g
4h
4i
p-MeC6H4, H
p-FC6H4, H
p-ClC6H4, H
p-MeOC6H4, H
2-naphthyl, H
C6H5, Me
100
100
100
100
100
100
100
100
100
100
98.6
97.9
97.8
R
R
R
R
R
R
R
R
R
R
99.0
> 99.0[e]
> 99.0
> 99.0
> 99.0
> 99.0
99.0
C6H5, Et
p-MeOC6H4, Me
p-ClC6H4, Me
p-MeC6H4, Me
4j
4k
10
[a] The reaction conditions were [Rh(cod)2]BF4:1c:substrate 0.01:0.012:1,
H2 pressure 1 atm, reaction time 12h, solvent CH 2Cl2, room temperature.
[b] Determined by 1H NMR and GC analysis. [c] Determined by chiral GC
on
a CP-Chirasil-Dex CB column. [d] Absolute configurations were
ascertained by comparison of the sign of optical rotation with that reported
in ref. [9b]. [e] Determined by HPLC on a Chiralcel OD column.
848
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1433-7851/02/4105-0848 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2002, 41, No. 5

COMMUNICATIONS
Tetrahedron: Asymmetry 1997, 8, 4027 4031; d) S.-g. Lee, C. W. Lim,
C. E. Song, K. W. Kim, C. H. Jun, J. Org. Chem. 1999, 64, 4445 4451.
[11] a) Review: J. F. Hartwig, Angew. Chem. 1998, 110, 2154 2177; Angew.
Chem. Int. Ed. 1998, 37, 2046 2067; b) A. S. Guram, S. L. Buchwald, J.
Am. Chem. Soc. 1994, 116, 7901 7902; c) J. Yin, S. L Buchwald, Org.
Lett. 2000, 2, 1101 1104.
[12] The enantioselectivity was slightly decreased at a lower reaction
temperature (95.7% ee at 68C) or higher hydrogen pressure
(95.2% ee at 40 psi) with ligand 1g. Other solvents such as acetone
(95.6% ee), THF (93.9% ee), and MeOH (94.2% ee) were also
examined with 1g as chiral ligand.
In summary, we have developed a new family of 1,4-
diphosphanes 1 with an imidazolidin-2-one backbone as chiral
ligands and showed their utility in the hydrogenation of a-
enamides. The modular construction of this ligand class allows
for wide structural diversity. Studies of this kind and
mechanistic investigations are underway.
Experimental Section
For details on the synthesis of 1a 1k and their precursors, see Supporting
Information.
[13] M. B. Smith, J. March, March×s Advanced Organic Chemistry, 5th ed.,
Wiley, New York, 2001, p. 174.
[14] a) T. Imamoto, S. Kikuchi, T. Miura, Y. Wada, Org. Lett. 2001, 3, 87
90; b) T. Morimoto, M. Chiba, K. Achiwa, Tetrahedron Lett. 1989, 30,
735 738.
General procedure for the asymmetric hydrogenation of enamide 4: 1
(0.0074 mmol) was added to
a solution of [Rh(cod)2]BF4 (2.5 mg,
0.0062mmol; cod ˆ 1,5-cyclooctadiene) in CH2Cl2 (2mL). After the
reaction mixture had been stirred at 208C for 20 min, enamide
(0.62mmol) was added. The hydrogenation was performed at 20 8C under
1 atm of hydrogen for 12h. The reaction mixture was passed through a
short silica gel column to remove the catalyst. The enantiomeric excess and
the reaction conversion were measured by chiral GC or HPLC without any
further purification.
4
Received: October 17, 2001 [Z18078]
MimickingMetallophosphatases: Revealinga
Role for an OH Group with No Libido**
[1] a) H. Takaya, T. Ohta, R. Noyori in Catalytic Asymmetric Synthesis
(Ed.: I. Ojima), VCH, New York, 1993, pp. 1 39; b) Comprensive
Asymmetric Catalysis, Vol. 1 III (Eds.: E. N. Jacobsen, A. Pfaltz, H.
Yamamoto), Springer, Berlin, 1999.
[2] Selected recent papers: a) T. Ireland, G. Grossheimann, C. Wieser-
Jeunesse, P. Knochel, Angew. Chem. 1999, 111, 3397 3400; Angew.
Marcello Forconi and Nicholas H. Williams*
Typically, descriptions of enzyme catalysis use multiple
simultaneous interactions between the substrate and the
active site to explain the remarkable efficiency which is
normally observed.[1] This poses the intriguing question–do
the different interactions operate cooperatively? That is, can a
catalytic interaction have a bigger impact when it acts in
concert with other complementary interactions than when it is
used alone. This is difficult to mimic with simple compounds;
usually when multiple interactions are introduced into a
model system, it is found that they act independently rather
than simultaneously, and such models generally do not rival
enzyme efficiency.[2] Here we report how catalysis of phos-
phate monoester hydrolysis by an intramolecular OH group
becomes much more effective when combined with catalysis
by a dinuclear metal ion complex.
We have incorporated phosphate monoesters 1a c into
dinuclear CoIII complexes 2a c. We have previously studied
this type of complex as a structural and functional model for
dinuclear metallophosphatases.[3] We wanted to investigate
the effect of combining intramolecular general acid catalysis
with this highly reactive core, as X-ray crystallography has
revealed that as well as the metal ions in the active sites of
metallophosphatase such as protein phosphatase-1 (PP-1) and
kidney bean purple acid phosphatase (KBPAP), potential
¡
Chem. Int. Ed. 1999, 38, 3212 3215; b) G. Francio, F. Faraone, W.
Leitner, Angew. Chem. 2000, 112, 1486 1489; Angew. Chem. Int. Ed.
2000, 39, 1428 1430; c) M. T. Reetz, G. Mehler, Angew. Chem. 2000,
112, 4047 4049; Angew. Chem. Int. Ed. 2000, 39, 3889 3890; d) C.-C.
Pai, C.-W. Lin, C.-C. Lin, C.-C. Chen, A. S. C. Chan, J. Am. Chem. Soc.
2000, 122, 11513 11514; e) U. Berens, M. J. Burk, A. Gerlach, W.
Hems, Angew. Chem. 2000, 112, 2057 2060; Angew. Chem. Int. Ed.
2000, 39, 1981 1894.
[3] a) T.-P. Dang, H. B. Kagan, J. Chem. Soc. Chem. Commun. 1971, 481;
b) H. B. Kagan, T. P. Dang, J. Am. Chem. Soc. 1972, 94, 6429 6433.
¬
¬
[4] a) J. Gawronski, K. Gawronska, Tartaric Acid and Malic Acid in
Synthesis, Wiley, New York, 1999, p. 332, and references therein.
Selected recent papers: b) W. Hu, C.-C. Chen, G. Xue, A. S. C. Chan,
Tetrahedron: Asymmetry 1998, 9, 4183 4192; c) M. Hayashi, Y.
Hashimoto, H. Takezaki, Y. Watanabe, K. Saigo, Tetrahedron:
Asymmetry 1998, 9, 1863 1866; d) V. Tararov, R. Kadyrov, T. H.
Riermeier, J. Holz, A. Bˆrner, Tetrahedron Lett. 2000, 41, 2351 2355.
[5] In Rh-catalyzed asymmetric hydrogenation, the orientation of phenyl
groups of chiral diphenylphosphane ligands dictates the enantiose-
lectivity. See: a) W. S. Knowles, Acc. Chem. Res. 1983, 16, 106 112;
b) J. M. Brown, P. L. Evans, Tetrahedron 1988, 44, 4905 4916; c) J. S.
Giovannetti, C. M. Kelly, C. R. Landis, J. Am. Chem. Soc. 1993, 115,
4040 4057; d) H. Brunner, A. Winter, J. Breu, J. Organomet. Chem.
1998, 553, 285 306.
[6] A. Miyashita, A. Yashuda, H. Takaya, K. Toriumi, T. Ito, T. Souchi, R.
Noyori, J. Am. Chem. Soc. 1980, 102, 7932 7934.
[7] G. Zhu, P. Cao, Q. Jiang, X. Zhang, J. Am. Chem. Soc. 1997, 119, 1799
1800.
[8] a) W. Li, X. Zhang, J. Org. Chem. 2000, 65, 5871 5874; b) Y.-Y. Yan,
T. V. RajanBabu, Org. Lett. 2000, 2, 4137 4140.
[9] Only a few ligands are effective for Rh-catalyzed asymmetric hydro-
genation of enamides: a) ref. [8]; b) M. J. Burk, Y. M. Wang, J. R. Lee,
J. Am. Chem. Soc. 1996, 118, 5142 5143; c) F.-Y. Zhang, C.-C. Pai,
A. S. C. Chan, J. Am. Chem. Soc. 1998, 120, 5808 5809; d) G. Zhu, X.
Zhang, J. Org. Chem. 1998, 63, 9590 9593; e) D. Xiao, Z. Zhang, X.
Zhang, Org. Lett. 1999, 1, 1679 1681; f) I. D. Gridnev, M. Yasutake,
N. Higashi, T. Imamoto, J. Am. Chem. Soc. 2001, 123, 5268 5276.
[10] Application of the C2-symmetric diamine 2 in the preparation of chiral
ligands: a) T. Oishi, M. Hirama, Tetrahedron Lett. 1992, 33, 639 642;
b) S.-g. Lee, C. W. Lim, C. E. Song, I. O. Kim, Tetrahedron: Asymme-
try 1997, 8, 2927 2932; c) S.-g. Lee, C. W. Lim, C. E. Song, I. O. Kim,
[*] Dr. N. H. Williams, M. Forconi
Chemistry Department
University of Sheffield
Sheffield S3 7HF (UK)
Fax : (‡44)114-2738673
E-mail: N.H.Williams@Sheffield.ac.uk
[**] We thank the Royal Society and Nuffield foundation for financial
support, and the BBSRC for a studentship (M.F.).
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
Angew. Chem. Int. Ed. 2002, 41, No. 5
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
1433-7851/02/4105-0849 $ 17.50+.50/0
849