Dioxygen mediated oxo-transfer to an amine and oxidative N-dealkylation chemistry with a dinuclear copper complex

Article abstract of DOI:10.1039/b009053k

Reaction of dioxygen with a dinuclear copper(I) complex of a new binucleating ligand is described, wherein a peroxodicopper(II) (Cu₂-O₂) intermediate leads to an oxo-transfer reaction to give an N-oxide of an N-benzyl internal ligand

Full text of DOI:10.1039/b009053k

View Article Online / Journal Homepage / Table of Contents for this issue
Dioxygen mediated oxo-transfer to an amine and oxidative N-dealkylation
chemistry with a dinuclear copper complex
a
a
a
a
a
b
Christiana Xin Zhang, Hong-Chang Liang, Eun-il Kim, Qing-Fen Gan, Zoltán Tyeklár, Kin-Chung Lam,
b
c
c
a
Arnold L. Rheingold, Susan Kaderli, Andreas D. Zuberbühler and Kenneth D. Karlin*
a
Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA. E-mail: karlin@jhu.edu
Department of Chemistry, University of Delaware, Newark, DE 19716, USA
Institut für Anorganische Chemie, University of Basel, CH-4056 Basel, Switzerland
b
c
Received (in Irvine, CA, USA) 8th November 2000, Accepted 15th February 2001
First published as an Advance Article on the web 14th March 2001
Reaction of dioxygen with a dinuclear copper(
a new binucleating ligand is described, wherein a peroxo–
dicopper(II) (Cu –O ) intermediate leads to an oxo-transfer
reaction to give an N-oxide of an N-benzyl internal ligand
substrate; additionally observed regioselective oxidative N-
dealkylation chemistry occurs.
I
) complex of
species [CuII
2
(D)(O
2
)]2+ 2 which gradually decomposes (vide
1
infra). Stopped-flow kinetic results show that the reversible (k /
2
2
k
k
2
21) formation of species 2 is first order in both 1 and O with
2
1 21
‡
21
1
= (10 ± 0.3) M
s
(183 K) [DH = (15.8 ± 0.8) kJ mol ,
‡
21
21
DS = (2135 ± 4) J K mol (183–206 K)}. The UV–VIS
spectrum of 2 [lmax = 360 (e 12 500), 514 nm (e 1220
3
21
21
dm mol cm )] shows features which are very similar to the
Cu –O peroxo–dicopper(II complexes established with
XYL6
[Cu (Nn)(O
Copper(
I
)–dioxygen reactivity studies,1–6 particularly those
2
2
,16
)
9
2+
involving actual substrate oxidations, are of interest as models
and Nn
ligands, [Cu
2
(XYL)(O
2
)]
and
2+
for metalloproteins which effect oxidative transforma-
2
2
2
)] , respectively, indicating that 2 also possesses a
tions,4
,5,7,8
and may serve in the development of oxidation
m-h :h side-on peroxodicopper(II) core.
2
reagents. One type of chemistry which we have extensively
examined involves O -binding and reactivity in the dinuclear
complexes where two copper( ) ions each coordinate to a bis[(2-
2-pyridyl)ethyl]amine (PY2) tridentate moiety which is linked
through the alkylamino nitrogens by a –(CH – (n = 3–5)
in the former case
-binding occurs, while in the latter situation, the
intermediate effects xylyl aromatic hydroxylation
chemistry. In our continuing effort to investigate the behavior of
Cu –O species and their reactivities toward internal substrates,
As mentioned, an N-benzyl moiety was designed into D as a
potential oxidizable site. Indeed, analysis of products obtained
2
I
2+
I
2 2
when O is reacted with [Cu (D)] 1 at 0 °C reveals that the N-
(
oxide D–O is obtained (Scheme 1); a labeling experiment
shows that the O atom is derived from dioxygen, suggesting an
oxygen atom transfer reaction has occurred.§ However,
2 n
)
,10
5,11
(
Nn),9
reversible O
Cu –O
or m-xylyl group (XYL);
2
II
2+
2 2
[Cu (D)(O )] (2) is not directly responsible for the formation
2
2
of D–O, since if it is allowed to stand at 280 °C, whereupon
decomposition occurs, no D–O forms [kinetics of decomposi-
2
4
21
‡
2
2
tion: k
2
= (4.5 ± 0.9) 3 10
s
at 183 K; DH = (44 ± 2)
we report here the use of a new ligand analogue D, with
similarities to Nn and XYL ligands, but possessing an N-benzyl
internal moiety. We describe the nature of the O
2
-binding to
form Cu –O species in the dicopper( ) complex of D, and novel
2
2
I
oxo-transfer and oxidative N-dealkylation chemistry. Such
reactions occur in copper proteins (e.g. peptidylglycine mono-
8
,12
oxygenase, PHM)
and heme cytochrome P-450 mono-
oxygenases.13
The copper(
I
) complex [CuI
reaction of 2 equiv. of [Cu (MeCN)
structure of 1 was obtained (Fig. 1).‡ While both copper(
2
(D)]2+ (1) was synthesized by
I
+
4
]
with D.† An X-ray
) ions
I
possess distorted tetrahedral tetracoordination, the binding is
highly unsymmetrical; Cu1 ligates to its PY2 tridentate plus the
central benzylamine nitrogen atom N7. The other Cu atom
(
Cu2) has instead as its fourth ligand a perchlorate oxygen atom
O5. We have previously observed related asymmetry utilizing
trinucleating ligands, either for tricopper(
14
15
I)
or tricopper(II)
complexes, wherein three copper ions bind a tridentate chelate,
but only one coordinates to a similarly ‘central’ amine nitrogen.
The copper ion moieties are well separated in 1, with Cu1…Cu2
Fig. 1 ORTEP diagram of the cationic portion of complex 1. Selected bond
lengths (Å): Cu1…Cu2 5.432, Cu1–N1 2135(3), Cu1–N3 1.979(3), Cu1–
N4 2.024(3), Cu1–N7 2.106(3), Cu2–N2 2.252(3), Cu2–N5 1.927(3), Cu2–
N6 1.925(3), Cu2–N6 1.925(3), Cu2–O5 2.551(3).
=
5.43 Å.
At 280 °C in dichloromethane, the dicopper( ) complex
I
I
2+
[
2 2 2
Cu (D)] 1 reacts with excess dioxygen to give a Cu O
DOI: 10.1039/b009053k
Chem. Commun., 2001, 631–632
This journal is © The Royal Society of Chemistry 2001
631

View Article Online
products which effect biomimetic regioselective oxidative N-
dealkylation chemistry. Additional studies will be directed
towards further structural and mechanistic understanding of the
chemistry described.
We are grateful to the National Institutes of Health (K. D. K.,
GM28962) and the Swiss National Science Foundation
(A. D. Z.) for support of this research.
Notes and references
†
Reaction of D with 2 equiv. of [Cu(MeCN)
which satisfactory C, H and N analyses were obtained.
Crystal data for C39 47Cl Cu ·3CH Cl . M = 1194.59, triclinic,
4 4 4 2
](ClO ) gave 1(ClO ) , for
‡
H
2
N O
2 7 8
2
2
¯
P1, a = 10.5816(2), b = 14.8247(2), c = 18.0045(2) Å, a = 112.4800(3),
b = 97.2565(2), g = 94.2666(2)°, V = 2565.53(6) Å , Z = 2, T = 173 K,
R(F) = 0.0469, R(wF ) = 0.1084. After accounting for the diCu cation and
two ClO
3
2
2
, a large void space of 644.8 Å3 containing numerous, but
4
chemically ill defined, difference peaks was resolved using SQUEEZE (A.
Spek, PLATON library), which determined the presence of a total of 241
electrons, or ca. six molecules of the recrystallization solvent CH Cl per
2 2
unit cell. Due the collective nature of this treatment of solvent, the atom list
does not contain individual atomic contributions. All other software was
contained in the SHELXTL (5.1) library (G. Sheldrick, Bruker AXS,
Madison, WI). CCDC 150146. See http://www.rsc.org/suppdata/cc/b0/
b009053k/ for crystallographic data in .cif or other electronic format.
Scheme 1
§ When the oxygenation reaction of 1 was carried out at 0 °C in CH
Cl
reaction,
an O atom is incorporated into D– O with 92% efficiency. Character-
2
for
2
18
1
0 min, D–O was isolated after workup in 47% yield. With an O
2
18
18
kJ mol2 , DS‡ = (62 ± 8) J K21 mol21 (198–293 K)]. We
suggest that the oxo-transfer reaction, having a relatively large
activation energy (i.e. higher temperatures are required to see
D–O product), is effected by a very reactive intermediate (A;
Scheme 1) derived from 2, which is formed in steady state.
Direct formation of the different oxidation products, i.e. without
formation of intermediate A, can be ruled out by the observation
that the overall rate constant k k /k21 shows a perfectly linear
1 2
Eyring plot between 198 and 293 K. Differentiation between the
various oxidation products thus must occur after the rate
1
1
ization of D–O: H NMR (CDCl
3
) d 2.92 (m, 20H), 3.08 (m, 4H), 4.17 (s,
2
H), 7.11–7.14 (m, 8H), 7.40–7.60 (m, 9H), 8.45 (d, 4H); positive ion FAB-
+
18
+
MS: D–O m/z: 630.4 (MH ), D– O m/z: 632.4 (MH ).
Organic products were isolated and characterized from the oxygenation
reaction of 1 in DMF at room temperature over 12 h: DA (71%) H NMR
(CDCl ) d 2.54 (t, 2H), 2.73 (t, 2H), 2.88 (m, 8H), 3.58 (s, 2H), 7.05–7.12
(m, 4H), 7.26–7.36 (m, 5H), 7.50–7.53 (m, 2H), 8.43 (d, 2 H) positive ion
¶
1
3
+
1
FAB-MS m/z: 361 (MH ); PY2 (51%) H NMR (CDCl
3
) d 2.47 (s, 1H),
3
.0-3.3 (m, 8H), 7.13–7.20 (m, 4H) 7.40–7.60 (m, 2H), 8.45 (d, 2H) positive
+
ion FAB-MS m/z: 228 (MH ); glyoxal (51.7%, isolated and quantified as its
2
1
,4-dinitrophenylhydrazone) H NMR (DMSO-d
6
) d 7.96 (d, 2H), 8.47 (q,
determining step k
2
.
2
H), 8.88 (s, 2H), 11.89 (s, 2H).
I
(D)]2+ 1 is carried out at room-
When the oxygenation of [Cu
2
temperature and for longer reaction times ( > 12 h), additional
products derived from oxidative N-dealkylation chemistry are
produced. DA is the amine byproduct from the hydroxylation of
one of the non-benzylic methylene carbons adjacent to the
middle nitrogen. The other fragment expected from this N-
dealkylation, an aldehyde, is not isolable; it is further oxidized
to yield glyoxal and PY2 (Scheme 1). Overall, DA, glyoxal and
PY2 form in excellent yield and material balance.¶ The fact that
this chemistry requires reaction times much longer than the
1
2
S. Schindler, Eur. J. Inorg. Chem., 2000, 2311.
M. Suzuki, H. Furutachi and H. Okawa, Coord. Chem. Rev., 2000,
200–202, 105.
3 A. G. Blackman and W. B. Tolman, Struct. Bonding (Berlin), 2000, 97,
179–211.
4
5
6
C. X. Zhang, H.-C. Liang, K. J. Humphreys and K. D. Karlin, in
Copper–Dioxygen Complexes and Their Roles in Biomimetic Oxidation
Reactions, ed. L. Simandi, Dordrecht, The Netherlands, 2001.
K. D. Karlin and A. D. Zuberbühler, in Formation, Structure and
Reactivity of Copper Dioxygen Complexes, ed. J. Reedijk and E.
Bouwman, New York, 1999.
II
2+
2 2
lifetime of the peroxo species [Cu (D)(O )] 2 (t1/2 = 0.01 s
at 298 K) indicates that as for the D–O formation, 2 is not
responsible for the oxidative N-dealkylation; in another case, a
K. D. Karlin, S. Kaderli and A. D. Zuberbühler, Acc. Chem. Res., 1997,
30, 139.
17
Cu
2
-O
2
intermediate is known to effect such reactivity. Here,
7 E. I. Solomon, U. M. Sundaram and T. E. Machonkin, Chem. Rev., 1996,
96, 2563.
8 J. P. Klinman, Chem. Rev., 1996, 96, 2541.
other complexes derived from the decomposition of 2, perhaps
II
II
II
II
Cu –OH–Cu or Cu –O–Cu species, may be responsible. We
note that anaerobic addition of 2 [Cu(H O) ](ClO and base to
9
H.-C. Liang, K. D. Karlin, R. Dyson, S. Kaderli, B. Jung and A. D.
Zuberbühler, Inorg. Chem., 2000, in press.
2
6
4 2
)
D, followed by heating, does lead to similar oxidative N-
dealkylation chemistry. The oxidative N-dealkylation chemistry
here appears to be regioselective, as benzaldehyde (which
would form by oxidation at the most easily oxidizable
methylene group) is formed in trace amounts only.
1
1
0 E. Pidcock, H. V. Obias, M. Abe, H.-C. Liang, K. D. Karlin and E. I.
Solomon, J. Am. Chem. Soc., 1999, 121, 1299.
1 E. Pidcock, H. V. Obias, C. X. Zhang, K. D. Karlin and E. I. Solomon,
J. Am. Chem. Soc., 1998, 120, 7841.
12 N. J. Blackburn, F. C. Rhames, M. Ralle and S. Jaron, JBIC, 2000, 5,
In conclusion, a new dicopper(
I
) compound, 1, has been
341.
synthesized with a built-in substrate and dissimilar copper(
I
)
13 M. Sono, M. P. Roach, E. D. Coulter and J. H. Dawson, Chem. Rev.,
1996, 96, 2841.
14 K. D. Karlin, Q.-F. Gan, A. Farooq, S. Liu and J. Zubieta, Inorg. Chim.
Acta, 1989, 165, 37.
I
2+
2
environments. [Cu (D)] 1 reacts with dioxygen yielding a
II
2+
2 2
peroxo species [Cu (D)(O )] 2 which decomposes leading to
two different ligand transformation reactions: (1) a reactive
species, which derives from 2, is competent to effect an oxo-
transfer reaction to give the N-oxide D–O. This appears to be a
rare known copper–dioxygen mediated amine to N-oxide
transformation. (2) With higher temperatures and over longer
1
5 S. T. Frey, H. H. J. Sun, N. N. Murthy and K. D. Karlin, Inorg. Chim.
Acta, 1996, 242, 329.
1
6 K. D. Karlin, M. S. Nasir, B. I. Cohen, R. W. Cruse, S. Kaderli and A. D.
Zuberbühler, J. Am. Chem. Soc., 1994, 116, 1324.
17 S. Mahapatra, J. A. Halfen and W. B. Tolman, J. Am. Chem. Soc., 1996,
118, 11 575.
2 2
time periods, the Cu –O species transforms to copper(II)
632
Chem. Commun., 2001, 631–632