Scheme 1. Synthesis of Dendritic Pyrphos Ligands 1-G a
n
a
2 2
Reagents and conditions: (a) DCC, DMAP, CH Cl , rt, 10 h.
behaviors of the core. However, it is still unclear how the
primary structure of the dendrimer biases its conformation
and consequently influences its catalytic properties. Here we
report a systematical study on the relationship between
dendrimer structure and catalytic property by choosing 3,4-
bis(diphenylphosphino)pyrrolidine (pyrphos, (3R,4R)-2) as
a model ligand. This study demonstrated that the structure
and conformation of the dendrimer significantly influenced
its catalytic activity.
catalytic activity and/or enantioselectivity compared to that
of the corresponding homogeneous catalyst. Recently, we
have reported a soluble poly(ethylene glycol)-supported
pyrphos, which showed highly catalytic efficiency due to
the homogeneous state during reaction. To make better-
defined immobilized catalysts for the study of the structure-
property relationships, we have now synthesized a number
of Fr e´ chet-type dendrimers in which one pyrphos unit was
located at the focal point. To the best of our knowledge, the
attachment of this diphosphine ligand at the focal point of a
dendrimer has not been reported to date.
1
2
Chiral diphosphines are the most widely used ligands in
the asymmetric catalytic hydrogenation of CdC and CdO
5
bonds. Chiral dendritic diphosphines have been reported by
The synthesis of new dendritic chiral pyrphos ligands is
outlined in Scheme 1. Polyether dendrons 3 with carboxyl
groups located at the focal point were synthesized by using
the convergent method reported by Fr e´ chet and co-workers;13
2 was synthesized according to the procedures reported by
6
7
2c,4e
3b,8
Brunner et al., Togni et al., Gade et al.,
and ourselves.
However, most of the ligands studied do not contain the
necessary functionalities for the convenient attachment to
9
dendrimers. Pyrphos, which was easily synthesized from
1
0
natural tartaric acid, contains a functional amino group to
which organic or inorganic supports may be directly attached.
Rhodium pyrphos and its derivatives have been studied for
the asymmetric hydrogenation of dehydroamino acid with
up to 99% ee. To recycle these expensive and oxygen-
sensitive catalysts, the complexes have been immobilized
on the Merrifield resin, silica gel, and TentaGel.1 However,
most of these immobilized catalysts have shown lower
Nagel and co-workers. A polyether dendrimer was chosen
to ensure catalyst stability under the reaction conditions. The
condensation reaction of 2 with 3 in the presence of 1,3-
dicyclohexylcarbodiimine (DCC) and 4-(dimethylamino)-
pyridine (DMAP) in dichloromethane at room temperature
gave chiral dendrimer ligands 1-G (n ) 0-3) in high yield.
n
0,11
These ligands were purified by flash column chromatography
1
13
31
and were characterized by H, C, and P NMR spectros-
copy, elemental analyses, and/or HRMS and MALDI-TOF
mass spectrometry. All results are consistent with the
compounds synthesized.
(
4) For examples of dendrimer catalysts with improved selectivity, see:
(
a) Ropartz, L.; Morris, R. E.; Foster, D. F.; Cole-Hamilton, D. J. Chem.
Commun. 2001, 361. (b) Ropartz, L.; Haxton, K. J.; Foster, D. F.; Morris,
R. E.; Slawin, A. M. Z.; Cole-Hamilton, D. J. J. Chem. Soc., Dalton Trans.
n
To investigate the efficiency of 1-G in asymmetric
2
002, 4323. (c) Mizugaki, T.; Murata, M.; Ooe, M.; Ebitani, K.; Kaneda,
K. Chem. Commun. 2002, 52. (d) Dahan, A.; Portnoy, M. Org. Lett. 2003,
, 1197. (e) Ribourdouille, Y.; Engel, G. D.; Richard-Plouet, M.; Gade, L.
H. Chem. Commun. 2003, 1228.
5) (a) Noyori, R.; Takaya, T. Acc. Chem. Res. 1990, 23, 345. (b) Tang,
catalysis, the rhodium-catalyzed asymmetric hydrogenation
of R-acetamido cinnamic acid (4) was chosen to be the model
reaction. The dendritic Rh catalysts were prepared in situ
5
(
W. J.; Zhang, X. M. Chem. ReV. 2003, 103, 3029.
n 2 4
via the reaction of 1-G with [Rh(COD) ]BF in dichloro-
(
6) Brunner, H.; Stefaniak, S.; Zabel, M. Synthesis 1999, 1776.
methane at room temperature for 30 min. All dendritic Rh-1
complexes were tested, and the preliminary results are
summarized in Table 1.
(
7) (a) K o¨ llner, C.; Pugin, B.; Togni, A. J. Am. Chem. Soc. 1998, 120,
1
0274. (b) Schneider, R.; K o¨ llner, C.; Weber, I.; Togni, A. Chem. Commun.
1
999, 2415.
(8) (a) Deng, G. J.; Fan, Q. H.; Chen, X. M.; Liu, D. S.; Chan, A. S. C.
Chem. Commun. 2002, 1570. (b) Deng, G. J.; Fan, Q. H.; Chen, X. M.;
Liu, G. H. J. Mol. Catal. A: Chem. 2003, 193, 21.
(11) During our study, fixation of pyrphos to the periphery of poly-
(propyleneimine) and PAMAM dendrimers was reported by Gade, L. H. et
al.; see refs 2c and 4e.
(12) Fan, Q. H.; Deng, G. J.; Lin, C. C.; Chan, A. S. C. Tetrahedron:
Asymmetry 2001, 12, 1241.
(13) Hawker, C. J.; Fr e´ chet, J. M. J. J. Am. Chem. Soc. 1990, 112,
7638.
(
9) Pyrphos first reported by Nagel and co-workers, see: Nagel, U.;
Kinzel, E.; Andrade, J.; Prescher, G. Chem. Ber. 1986, 119, 3326.
10) For immobilized Pyrphos-containing catalysts, see: (a) Nagel, U.
(
Angew. Chem., Int. Ed. Engl. 1984, 23, 435. (b) Nagel, U.; Kinzel, E. J.
Chem. Soc. Chem. Commun. 1986, 1098. (c) Nagel, U.; Leipold, J. Chem.
Ber. 1996, 129, 815.
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Org. Lett., Vol. 6, No. 9, 2004