Structurally Defined Catalysts for Enantioselective Oxidative Coupling Reactions

Article abstract of DOI:10.1002/anie.200351978

Copper(II)-based complex catalysts (see crystal structures) were prepared and characterized by X-ray crystallography. They were shown to be active catalysts for asymmetric oxidative coupling of 2-naphthol with high enantioselectivity.

Full text of DOI:10.1002/anie.200351978

Communications
larly noteworthy because BINAP greatly expanded the
synthetic utilities of binaphthol in asymmetric catalysis.[2] In
light of the wide-ranging and important applications of these
compounds, catalytic asymmetric preparation of chiral
binaphthols and improvements in the enantioselectivity of
the associated catalysts have continued to attract the atten-
tion of many researchers.[3]
Existing catalysts for the asymmetric preparation of chiral
binaphthols include copper complexes of chiral amines or
their derivatives[4] and chiral VIVO complexes with either one
or two stereogenic metal centers.[5] Recently, dimeric cop-
[4b,e,f]
per(ii)complexes
or dinuclear VIVO complexes[5d,e] have
been shown to be better catalysts with a high enantioselec-
tivity. In the above reports, the catalytic metal complexes
were prepared in situ by reacting a chiral ligand with a desired
metal ion (CuI, CuII, or VIVO). Generally, this method
produces at least three species in solution: metal-free ligand,
mononuclear, and dinuclear complexes. However, it is not
easy to identify the active species that contribute to the
overall reaction rate. Furthermore, the X-ray crystal struc-
tures of the above catalysts have never been determined, and
this has restricted mechanistic investigations aimed at further
improving the catalytic enantioselectivity and robustness.
Given the success of Jacobsen's salen catalysts[6] in a broad
range of asymmetric catalytic reactions, we decided to inves-
tigate whether coupled salen complexes would catalyze reac-
tions that require two catalytic centers. Herein we describe
the syntheses and crystal structures of a family of dicopper
catalysts for the asymmetric oxidative coupling of 2-naphthol.
The reaction of (1R,2R)-1,2-diaminocyclohexane (R,R-
DACH)with 2,6-diformylphenol or its derivatives in the
presence of CuII gave yellow-green solids of 1a–c (Scheme 1),
Asymmetric Oxidative Coupling
Structurally Defined Catalysts for
Enantioselective Oxidative Coupling Reactions**
Jian Gao,* Joseph H. Reibenspies, and
Arthur E. Martell+
Pure binaphthol enantiomers and their derivatives are
important chiral ligands for a wide range of asymmetric
syntheses.[1] The facile conversion of binaphthol into 2,2’-
(diphenylphosphanyl)-1,1’-binaphthyl (BINAP)is particu-
[*] Dr. J. Gao, Dr. J. H. Reibenspies, Prof. A. E. Martell+
Department of Chemistry, Texas A & M University
College Station, Texas 77843-3255 (USA)
Fax: (+1)979-845-4719
E-mail: gao@mail.chem.tamu.edu
[+] Sadly, Dr. Arthur E. Martell passed away on October 15, 2003. He
was a fine chemist, a stimulating advisor, and always full of ideas. It
was our privilege to work with him and we shall always be indebted
to him for sharing his scientific insight with us. Along with the
chemistry community, we mourn his passing.
[**] This research program was supported by a grant from the Welch
Foundation A-259. We thank Dr. Li Sun for helping with the revision
of the manuscript.
Scheme 1. Structures of Schiff base dicopper(ii) complexes 1a–c, mac-
rocyclic ligands 2a–c, and polyamino dicopper(ii) complexes 3a–c.
6008 ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/anie.200351978
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Angewandte
Chemie
which were recrystallized from DMF/MeOH. X-ray crystal-
structure analysis showed that 1b contains two CuII centers,
each coordinated in a N2O2-coordination compartment (Fig-
ure 1a). Within the macrocycle, the Schiff-base bonds are
essentially coplanar with the adjacent phenolic rings, and the
CuII ions reside in this plane. Each CuII ion adopts a square-
pyramidal geometry with a coordinated methanol molecule in
the axial direction. The space-filling representation of the
dicationic complex (Figure 1b)exhibits D2 symmetry and a
substantial orbital overlap of the two Cu centers (Cu1–Cu2
distance, 2.8887 Š).
oligomer. After adopting a metal-template approach, fol-
lowed by hydrogenation, 2a–c were successfully prepared in
high yields (65–85%). ESI MS spectrum of 2b (Figure 2)
(m/z, [2b+H+] 493.3476; [2b+2H+] 247.1748)shows the
correct molecular weight, and 1H NMR and 13C NMR spectra
are entirely consistent with the proposed structure. Dicop-
per(ii)complexes 3a–c were readily prepared by reacting the
corresponding macrocyclic ligands with 2 equivalents of CuII
in MeOH.
The preparation of 2a–c was initially attempted by the
Schiff-base condensation of R,R-DACH with the correspond-
ing dialdehyde at room temperature, but this led to an
Figure 2. ESI MS spectrum of the macrocyclic ligand 2b.
By utilizing a similar synthetic approach, Schiff base
dicopper(ii)complex 1d, the chiral polyamino macrocycle 2d,
and the corresponding dicopper(ii)complex 3d were success-
fully prepared (Scheme 2). The X-ray crystal structure of 1d
(Figure 3)shows that the whole molecule adopts a starlike
À
shape with four extended phenyl groups. The C H bonds
from the stereogenic centers in both 1b and 1d are essentially
perpendicular to the N4O2-plane (Figure 4), giving an a,b,a,b-
Figure 1. a) ORTEP drawing of 1b. Selected bond lengths [Š] and
angles [8]: Cu(1)-Cu(2) 2.8887(9), Cu(1)-N(1) 1.878(6), Cu(1)-O(1)
1.879(7), Cu(1)-O(2) 1.889(6), Cu(1)-N(2) 1.913(7), Cu(1)-O(3)
2.303(5); N(1)-Cu(1)-O(1) 92.7(3), N(1)-Cu(1)-O(2) 168.1(2), O(1)-
Cu(1)-O(2) 81.5(2), N(1)-Cu(1)-N(2) 91.3(3). b) Space-filling represen-
tation of 1b: gray: carbon, red: oxygen, blue: copper.
Scheme 2. Structures of Schiff base dicopper(ii) complex 1d, macrocy-
clic ligand 2d, polyamino dicopper(ii) complex 3d, and the control
compound 4.
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The oxidative coupling of 2-naphthol was employed as a
model reaction to compare the catalytic activity and enantio-
selectivity of the dicopper(ii)macrocycle complexes, 1a–d and
3a–d. All reactions were carried in the presence of the
catalysts (10 mol%)in CCl 4 at 08C with molecular oxygen as
oxidant (Table 1). The use of complex 1b resulted in a yield of
Table 1: Catalytic enantioselective coupling of 2-naphthol in the presence
of catalysts (10 mol%).[a]
Entry
Catalyst T [8C] t [days] Yield [%][b]
ee [%][c]
Config.
1
2
3
4
5
6
7
8
9
1a
1b
1b
1b
1c
1d
3a
3b
3b
3b
3c
3d
0
0
10
20
0
0
0
0
7
7
5
3
7
7
7
7
5
3
7
7
75
79
80
89
80
79
92
84
90
93
85
85
69
82
61
45
84
80
84
86
74
62
87
88
S
S
S
S
S
S
S
S
S
S
S
S
10
20
0
10
11
12
0
[a] The reaction was carried out at 0, 10 or 208C in the presence of
10 mol% of catalyst in CCl4 solution. [b] Yield of isolated product. [c] The
enantiomeric excess was determined by HPLC (Chiralpak AD) and the
absolute configuration was assigned by comparison to literature.
79% and a moderate enantioselectivity of 82% ee (Table 1,
entry 2). When polyamino complex 3b was used (Table 1,
entry 8), slightly increases in the ee value (86%)and the yield
(84%)were observed. In general, polyaza complexes are
more robust than their corresponding Schiff base complexes
in terms of reproducibility and stability. Catalytic efficiency
seems to be insensitive to the bulk of the peripheral groups
(compare 1a–c and 3a–c series). At higher temperatures, the
reaction rate increases, but lower enantioselectivities are
observed. For instance, the ee value for 1b decreased by 37%
when the temperature was increased from 0 to 208C.
Increased bulk of the diamino residues (compare 1b with
1d and 3b with 3d)does not significantly affect the
enantioselectivity. Furthermore, the control compound with
one metal center (4 with C2 symmetry)leads to a low
enantioselectivity at 08C (only 19% ee). These results suggest
Figure 3. a) ORTEP drawing of 1d. Selected bond lengths [Š] and
angles [8]: Cu(1)-Cu(2) 2.8989(9), Cu(1)-N(1) 1.884(11), Cu(1)-O(1)
1.907(4), Cu(1)-O(2) 1.903(4), Cu(1)-N(2) 1.887(5), Cu(1)-O(1me)
2.305(5); N(1)-Cu(1)-O(1) 94.1(2), N(1)-Cu(1)-O(2) 171.9(2), O(1)-
Cu(1)-O(2) 80.07(18), N(1)-Cu(1)-N(2) 90.5(3). b) Space-filling repre-
sentation of 1d: gray: carbon, red: oxygen, blue: copper.
chiral molecule reminiscent of the chiral porphyrin-amino
derivative a,b,a,b-TAPP.[7] Complex 4 was synthesized by
condensation of 2 equivalents of salicylaldehyde with 1R,2R-
diphenylethylenediamine (R,R-DPEN)in the presence of
CuII. This complex serves as a control in the following
catalytic experiments.
À
Figure 4. Alternate views of 1b and 1d, showing the positions of the chiral C H bonds.
6010
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that a rigid dinuclear platform is essential for high enantio-
selectivity.
atoms of the chiral cyclohexyl rings should favor the
orientation shown in Figure 5A. This should produce the
S product, 8. The above hypothesis is essentially the same as
the pathway 1 mentioned above. This seems to be reasonable
given the fact that the two catalytic centers are structurally
symmetric. However, more quantitative experiments are
required to completely verify our hypothesis or to disprove
the remaining two reaction pathways.
The CuII complex mediated oxidative coupling can
proceed through three mechanistic pathways:[4e,g] 1)homo-
lytic coupling of two radical species, 2)radical insertion of one
À
aryl into the C H bond of another aryl, and 3)reaction of an
anion with a carbocation. For the coupling reaction mediated
by 1b (Figure 5), a substrate molecule may undergo ligand
exchange with MeOH (on Cu1)to form a Cu II–substrate
complex 5, which is followed by the generation of a radical
intermediate 6, which results from one-electron transfer from
the substrate to CuII. Simultaneously, the same process may
occur on the Cu2 center. Minimization of steric interactions
between the radical intermediates and the axial hydrogen
Experimental Section
[1b–Cu2](ClO4)2·4CH3OH: A solution of 2-hydroxy-5-methyl-1,3-
benzenedicarboxaldehyde (0.1 mmol)was added dropwise to a
solution of Cu(ClO4)2 (0.1 mmol)and R,R-DACH (0.1 mmol)in
EtOH (10 mL). After stirring for 4 h, a yellow-green product was
obtained in 56% yield. Elemental analysis: calcd (%)for
C34H50Cl2Cu2N4O14: C 43.6, H 5.4, N 6.0; found: C 43.6, H 5.5, N
6.0. Green crystals were obtained by diffusion of MeOH into a
solution of the sample in N,N-dimethylformamide. Crystal dimen-
sions: 0.3 ” 0.3 ” 0.02 mm3, C34H50Cl2Cu2N4O14, M = 936.76, mono-
clinic, space group P2(1), a = 11.996(3)Š, b = 13.439 (3)Š, c =
12.303(3)Š, a = 90.08, b = 102.747(5)8, g = 90.08, V= 1934.5(8)Š 3,
Z = 2, 1calcd = 1.6478 cmÀ3, F(000) = 976, T= 110(2)K, Mo Ka radia-
tion, l = 0.71073 Š. A total of 7901 independent reflections (Rint
=
0.0371)were obtained. Nonhydrogen atoms were refined with
anisotropic thermal parameters. Hydrogen atoms were included in
the calculated positions refined with isotropic thermal parameters
riding on those of the parent atoms. Full-matrix least-squares
refinement on F2 converged to R1 = 0.0786, wR2 = 0.2078 (I > 2a(I))
with
a
goodness of fit F2 = 1.060. CCDC-210825 contains the
supplementary crystallographic data for this compound. These data
can be obtained free of charge via www.ccdc.cam.ac.uk/conts/
retrieving.html (or from the Cambridge Crystallographic Data
Centre, 12, Union Road, Cambridge CB21EZ, UK; fax:
(+ 44)1223-336-033; or deposit@ccdc.cam.ac.uk).
[1d–Cu2(ClO4)2]·4CH3OH: The complex was prepared by fol-
lowing a similar procedure to that described above (68% yield).
Elemental analysis: calcd (%)for C 50H54Cl2Cu2N4O14: C 53.0, H 4.8,
N 5.0; found: C 53.0, H 4.7, N 5.1. Crystal data: green block 0.05 ”
0.2 ” 0.3 mm3; C50H54Cl2Cu2N4O14, M = 1132.95, monoclinic, space
group P2(1), a = 15.8000(2)Š, b = 9.4030 (12)Š, c = 16.883(2)Š,
a = 90.08, b = 98.298(2)8, g = 90.08, V= 248.9(6)Š 3, Z = 2, 1calcd
=
1.516 cmÀ3
,
F(000) = 1172, T= 110(2)K, Mo Ka radiation, l =
0.71073 Š. A total of 5485 independent reflections (Rint = 0.0323)
were obtained. Full-matrix least-squares refinement on F2 converged
to R1 = 0.0419, wR2 = 0.0986 (I > 2a(I)) with a goodness of fit F2 =
1.020. CCDC-210826 contains the supplementary crystallographic
data for this compound. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge CB21EZ,
UK; fax: (+ 44)1223-336-033; or deposit@ccdc.cam.ac.uk).
2b: R,R-DACH (15 mmol)in MeOH (200 mL)was added
dropwise to a stirred solution of 2-hydroxy-5-methyl-1,3-benzenedi-
carboxaldehyde (99%; 2.15 g, 15 mmol)in the presence of Pb II(OAC)2
in MeOH (300 mL). The yellow solid formed was filtered, washed
with MeOH, dried in air, and suspended in MeOH (50 mL). Solid
NaBH4 (4.0 g, 100 mmol)was used to reduce the metal complex at
08C in an ice bath. The suspension was magnetically stirred for about
2 h at room temperature. Water (5 mL)was added to neutralize
excess unreacted NaBH4. The resulting yellow-colored solution was
filtered to remove any suspended material. The filtrate was diluted
with water (100 mL), acidified (pH 2.0) with H2SO4 (8m), and was
then filtered. The filtrate was treated with aqueous ammonia
(12.5 ml), and was then extracted with chloroform (3 ” 50 mL). The
combined organic layer was washed with water, dried with Na2SO4,
and the solvent removed on a rotary evaporator nearly to dryness.
Figure 5. Illustration of enantioselectivity in 1b-catalyzed oxidative cou-
pling of 2-naphthol. Viewed from above the basal plane of the com-
plex. Hydrogen atoms are omitted for clarity: green: copper, blue:
nitrogen, gray: carbon, red: oxygen, black: stereogenic carbon center,
which sterically hinders the substrate molecules.
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The crude product was purified by column chromatography (silica gel,
CH2Cl2/MeOH ~ 1:1)and was identified as 2b (75% yield). ESI MS:
m/z: 493.3478 [M+H]+; calcd for C30H44N4O2: 492.3464, m.p. 2088C;
[a]2D5 = À 21.7 (c = 0.01, CH2Cl2); 1H NMR (CDCl3): d = 1.17–1.80 (m,
8H; CH2 of cyclohexane), 2.31 (m, 3H; CH3-Ar), 3.79 (s, 2H; CH of
cyclohexane), 4.30–4.52 (m, 4H; CH2-Ar), 7.36 ppm (s, 2H; Ar-H);
13C NMR (CDCl3): d = 20.78 (CH2 of cyclohexane), 24.75 (CH2 of
cyclohexane), 44.74 (CH of cyclohexane), 54.81 (CH2-Ar), 121.86
(Ar-H), 133.75 (C(Ar)-CH2), 134.36 (C(Ar)-CH3), 152.10 ppm
(C(Ar)-OH). Elemental analysis: calcd (%) for C30H44N4O2: C
73.13, H 9.00, N 11.37; found: C 73.13, H 9.06, N 11.38%.
2d: Prepared by a similar reaction procedure from R,R-DPEN as
that for 2b. Yield: 80%; ESI MS: m/z: 689.36 [M+H]+; calcd for
C46H48N4O2: 688.38; m.p. 1648C; [a]2D5 = + 31.3 (c = 0.01, CH2Cl2);
1H NMR,(CDCl3): d = 2.18 (s, 3H; CH3-Ar), 3.80–3.92 (d, 2H; CH-
Ar), 4.76 (m, 4H; CH2-Ar), 7.08–7.42 (m, 12H; Ar-H), 7.78 ppm (s,
1H; OH); elemental analysis: calcd (%) for C 46H48N4O2: C 80.20, H
7.02, N 8.13, found: C 80.11, H 7.06, N 8.10%.
Received: May 26, 2003 [Z51978]
Keywords: asymmetric catalysis · binaphthols · copper ·
.
cross-coupling · enantioselectivity
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