Amino acid-derived ligands for transition metals: Catalysis via a minimalist interpretation of a metalloprotein

Full text of DOI:10.1021/ja972135j

J. Am. Chem. Soc. 1997, 119, 10865-10866
10865
Scheme 1
Amino Acid-Derived Ligands for Transition
Metals: Catalysis via a Minimalist Interpretation of
a Metalloprotein
Brian Dangel, Michael Clarke, Jay Haley,
Dalibor Sames, and Robin Polt*
Department of Chemistry, UniVersity of Arizona
Tucson, Arizona 85721
ReceiVed June 26, 1997
Chemists and enzymologists have attempted to understand
and duplicate the incredible efficiency of metalloproteins for
over 70 years now.1 Of particular interest are the metallopor-
phyrins which display a wide variety of chemical reactivity,
principally due to their ability to complex almost any of the
transition metals.2 Most of the metalloporphyrin chemistry has
been developed in a “self-governing field,” far removed from
the practical constraints imposed by the requirements of catalysis
and organic synthesis.3 Exquisitely powerful and selective
catalysts have been designed based on the porphyrin ring
system,4 but the lengthy synthesis required to produce these
metal-binding moieties may preclude their widespread use as
practical chemical catalysts.5 A more direct approach is to use
the peptide backbone to bind metals6a or a peptide-derived
macrocycle.6b,c
Since the majority of amino acids in a typical protein are
structural in nature, and thus far removed from the active site,
it should be possible to replace them with a simple achiral
diamine which would serve to bring only two optically active
amino acid residues into close proximity to form a simplified
“active site.” 7 A short, chemically efficient synthesis of the
ligand system with chirality incorporated from the amino acids
should be possible, and a variety of transition metal-binding
geometries should be accessible. This allows for development
of a variety of catalysts. Creation of new symmetry elements
centered on the metal would be ideal8 and should allow for the
efficient transfer of chirality to the substrate upon catalysis.
While only C2-symmetric tetradentate complexes9 will be
described in this paper, many other geometries are possible with
the introduction of other linkers and more functionalized amino
acids capable of metal binding.10
agents (DCC or BOP) to provide the Boc-protected bis-amide
2 in excellent yield. The Boc groups were quantitatively
removed with HCl in methanol to yield crystalline 3, which
was treated with diphenylketimine to yield the Schiff base 4.11
Reaction of 4 with NiBr2 in refluxing MeOH in the presence
of the Et3N provided the deep maroon, crystalline complex 5a
which was air-stable and water-stable and was readily chro-
matographed on SiO2. This low-spin complex was characterized
1
by H-NMR and provided crystals suitable for single-crystal
X-ray analysis. Similarly, reaction of 4 with CuCl2 in DMF
at room temperature with the much stronger base DBU provided
brown crystals of 5b after flash chromatography on SiO2. This
paramagnetic complex was subjected to EPR analysis.
A single crystal of 5a was subjected to X-ray analysis, and
a preliminary structure (R ≈ 8%) was obtained (Figure 1). Two
molecules, a totally symmetric molecule 5a′, possessing a C2
axis, and an unsymmetric molecule 5a′′ were observed in the
The synthesis of the NiII and CuII complexes 5a and 5b is
depicted in Scheme 1. Phenylenediamine (1) was doubly
acylated with Boc-L-phenylalanine with various condensation
R
unit cell, differing predominantly by rotation about one C-
âC bond in a phenylalanine residue. Thus, the solid-phase X-ray
data strongly supported the NMR data obtained in CDCl3
solution. In addition to rotation about the phenylalanine side
chain, the two conformations differed in metal geometry as well
(Table 1). In both molecules the NisNdCPh2 bond lengths
(1) (a) Sumner J. B. J. Biol. Chem. 1926, 69, 435-441. (b) Lippard, S.
J. Science 1995, 268, 996-997. (c) Jabri, E.; Carr, M. B.; Hausinger, R.
P.; Karplus, P. A. Science 1995, 268, 998-1004.
(2) (a) Porphyrins and Metalloporphyrins; Smith, K. M., Ed.; Elsevier:
Amsterdam, 1975. (b) The Porphyrins; Dolphin, D., Ed.; Academic Press:
New York, 1979.
(3) Meunier, B. Bull. Soc. Chim. Fr. 1986, 578-594.
(4) Holm, R. H. Chem. ReV. 1987, 87, 1401-1449.
(8) The idea for these complexes sprang from work in which [7]-helicenes
bearing terminal cyclopentadienyl anions were used to introduce optical
activity into transition metals: (a) Dewan, J. C. Organometallics 1983, 2,
83-88. (b) Sudhakar, A.; Katz, T. J. J. Am. Chem. Soc. 1986, 108, 179-
181. (c) Gilbert, A. M.; Katz, T. J. Geiger, W. E.; Robben, M. P.; Rheingold,
A. L. J. Am. Chem. Soc. 1993, 115, 3199-3211. (d) Dai, Y.; Katz, T. J.
Angew. Chem., Int. Ed. Engl. 1996, 35, 2109-2111. (e) Kawamoto, T.;
Hammes, B.S.; Haggerty, B.; Yap, G. P. A.; Rheingold, A. L.; Borovik, A.
S. J. Am. Chem. Soc. 1996, 118, 285-286.
(9) (a) Groves, J. T.; Viski, P. J. Org. Chem. 1990, 55, 3628-3634. (b)
Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. J. Am. Chem.
Soc. 1990, 112, 2801-2803. (c) Irie, R.; Noda, K.; Ito, Y.; Matsumoto, N.;
Katsuki, T. Tetrahedron Lett. 1990, 31, 7345-7348. (d) Terekohova, M.
I.; Beokon’, Y. N.; Maleev, V. I.; Chernoglazova, N. I.; Kochetkov, K. A.;
Belikov, V. M.; Petrov, E. S. IzV. Akad. Nauk S.S.S.R. 1986, 905-909. (f)
Holm, R. H. See ref 4.
(5) (a) Groves, J. T.; Myers, R. S. J. Am. Chem. Soc. 1983, 105, 5791-
5796. (b) Konishi, K.; Oda, K.; Nishida, K.; Aida, T.; Inoue, S. J. Am.
Chem. Soc. 1992, 114, 1313-1317. (c) Naruta, Y.; Ishihara, N.; Tani, F.;
Maruyama, K. Bull. Chem. Soc. Jpn. 1993, 66, 158-166. (d) Collman, J.
P.; Lee, V. J.; Kellen-Yuen, C. J.; Zhang, X.; Ibers, J. A.; Brauman, J. I. J.
Am. Chem. Soc. 1995, 117, 692-703. (e) Gross, Z.; Ini, S. J. Org. Chem.
1997, 62, 5514-5521. (f) Furusho, Y.; Kimura, T.; Mizuno, Y.; Aida, T.
J. Am. Chem. Soc. 1997, 119, 5267-5268. (g) Kobayashi, N.; Kobayashi,
Y.; Osa, T. J. Am. Chem. Soc. 1993, 115, 10994-10995.
(6) (a) Margerum, D. W. Pure Appl. Chem. 1983, 55, 23-34. (b) Hsiao,
Y.; Hegedus, L. S. J. Org. Chem. 1997, 62, 3586-3591. (c) Busch, D. H.
Acc. Chem. Res. 1978, 11, 392-400.
(7) Several groups have used cyclic dipeptides (diketopiperazines) as
asymmetric catalysts. We like to think of these small peptides as “microen-
zymes.” Cf.: (a) Tanaka, K.; Mori, A.; Inoue, S. J. Org. Chem. 1990, 55,
181-185. (b) Danda, H.; Nishikawa, H.; Otaka, K. J. Org. Chem. 1991,
56, 6740-6741. (c) Lipton, M.; Iyer, M. S.; Gigstad, K.M.; Namdev, N.
D. J. Am. Chem. Soc. 1996, 118, 4910-4911. With the incorporation of a
metal binding site it is natural to refer to these moieties as “micro-
metalloenzymes.”
(10) In a similar fashion L-Phe has been reacted with ethylenediamine,
propylenediamine, 1,3-diaminonaphthalene, and diaminomaleonitrile (DAMN)
to produce other tetradentate ligands. o-Phenylenediamine has been reacted
with L-Ser and L-His to produce hexadentate ligands. This work will be
reported in full elsewhere.
(11) O’Donnell, M. J.; Polt, R. L. J. Org. Chem. 1982, 47, 2663-2666.
S0002-7863(97)02135-5 CCC: $14.00 © 1997 American Chemical Society

10866 J. Am. Chem. Soc., Vol. 119, No. 44, 1997
Communications to the Editor
Simulation of the spectra based on QPWA is in progress. From
preliminary data we can conclude that the complex is qualita-
tively similar to CuII tetraphenylporphyrin complexes, but with
increased tetrahedral distortion from square planarity.13 Strong
evidence for the helical nature of these complexes was provided
by the unusually large optical rotation upon insertion of the
metal.14
Since several groups showed previously that NiII can catalyze
the epoxidation of olefins,15 the epoxidation of simple cis- and
trans-olefins was examined using complex 5a and commercial
bleach (NaOCl) as an oxidant. No attempt was made to
optimize the reactions. The trans-epoxides were observed as
the major product in every case, regardless of the starting olefin
geometry. While the ee’s were not large (∼4%), turnover
numbers of 12-14 were observed with trans-â-methylstyrene
and 5a, indicating that the ligand system can function under
the conditions of catalysis. Most likely, the epoxidation does
not occur on the metal,14d but is mediated by the hypochlorite
•
oxidation product OCl.
Several other ligands constructed from various diamines and
amino acids have also been prepared using the same methodol-
ogy outlined above. The insertion of other transition metals
and the examination of the catalytic activity of the resulting
complexes are also in progress. Since these catalysts are formed
easily in four steps from readily available chiral starting
materials, it is anticipated that they will find widespread
applications.
Figure 1.
Table 1
5a′
5a′′
Selected Bond Lengths (Å)
Ni-N(1)
Ni-N(2)
Ni-N(3)
Ni-N(4)
1.99
1.88
1.87
1.98
1.98
1.87
1.83
1.93
Acknowledgment. This paper is dedicated to Professor Dr. Dieter
Seebach on the occasion of his 60th birthday. We thank Dr. Michael
Bruck for the X-ray structure determination, Dr. Arnold Raitsimring
for the electron paramagnetic resonance spectra and interpretation, and
Professor David Wigley for help with the cyclic voltammetry experi-
ments. M.C. thanks the Hughes Foundation for financial support. We
are grateful for financial support from the National Science Foundation
(CHE-9526909).
Selected Bond Angles (deg)
N(1)-Ni-N(2)
N(2)-Ni-N(3)
N(3)-Ni-N(4)
N(1)-Ni-N(4)
81.5
85.6
82.5
110.4
85.0
83.2
82.0
110.7
rms dev from plane (Å)
0.020
0.119
JA972135J
(12) . Glass: g ≈ 2.18 MHz and A| ≈ 625 MHz. Liquid: gav ) 2.093
||
were somewhat longer than the NisN-CdO bond lengths, and
the complexes are more trapezoidal, relative to porphyrin
complexes, which tend to be more planar and strictly square.
While the symmetric 5a′ showed almost no deviation from
square planarity, the four nitrogens in 5a′′ showed a noticeable
tetrahedral distortions0.119 Å rms deviation overall from the
ideal plane. The Ph2CdN- groups were observed to be
“stacked” in both cases, a factor which undoubtedly adds to
the “helical twist” about the metal.
Complex 5b was purified by flash chromatography and
recrystallization and subjected to electron spin resonance
spectroscopy at 9.447 GHz. The EPR parameters were evalu-
ated from a combination of glass and liquid-state spectra.12
MHz and Aav ≈ 284 MHz, and g ) 2.05 MHz and A ≈ 114 MHz.
Assuming the hyperfine interaction with CuII is isotropic, the magnitude is
37-42 MHz.
(13) (a) Greiner, S. P.; Rowlands, D. L.; Kreilick, R. W. J. Phys. Chem.
1992, 96, 9132-9139. (b) Wang, Y.; Stack, T. D. P. J. Am. Chem. Soc.
1996, 118, 13097-13098.
(14) 4: [R]D ) -156° (c ) 0.560 g/100 mL of CHCl3). 5a: [R]D
)
-494° ( 11° (c ) 0.002 875 g/100 mL of CHCl3). 5b: [R]D ) -2020° (
140° (c ) 0.001 875 g/100 mL of CHCl3). This last rotation is reminiscent
of the helicenes in terms of the large degree of optical activity: Laarhoven,
W. H.; Prinsen, W. J. C. Topics Current Chem. 1984, 125, 63.
(15) (a) Koola, J. D.; Kochi, J. K. Inorg. Chem. 1987, 26, 908-916. (b)
Kinneary, J. F.; Wagler, T. R.; Burrows, C. J. Tetrahedron Lett. 1988, 29,
877-880. (c) Nam, W.; Valentine, J. S. J. Am. Chem. Soc. 1993, 115, 1772-
1778. (d) Kinneary, J. F.; Albert, J. S.; Burrows, C. J. J. Am. Chem. Soc.
1996, 110, 6124-6129.