Redox-triggered interconversion between piperidine chair conformations in a Cu(I/II) complex

Article abstract of DOI:10.1021/ol061364k

A redox-induced six-membered ring chair-chair conformational interconversion in a copper-coordinated trans-piperidine tripodal ligand is demonstrated. Each group of the 1,2,3-substituted ring can potentially ligate the metal; two equatorial groups ligate the metal in the Cu^I state leaving a disassociated, axial group. However, all three groups (two axial and one equatorial) ligate the metal in the Cu^II state. Exciton-coupled circular dichroism (ECCD) and 2D NMR were used to characterize the structures.

Full text of DOI:10.1021/ol061364k

ORGANIC
LETTERS
2
006
Vol. 8, No. 18
907-3910
Redox-Triggered Interconversion
between Piperidine Chair Conformations
in a Cu(I/II) Complex
3
Jing Zhang and James W. Canary*
Department of Chemistry, New York UniVersity, New York, New York 10003
canary@nyu.edu
Received June 4, 2006
ABSTRACT
A redox-induced six-membered ring chair
demonstrated. Each group of the 1,2,3-substituted ring can potentially ligate the metal; two equatorial groups ligate the metal in the Cu state
leaving a disassociated, axial group. However, all three groups (two axial and one equatorial) ligate the metal in the Cu state. Exciton-coupled
−
chair conformational interconversion in a copper-coordinated trans-piperidine tripodal ligand is
I
II
circular dichroism (ECCD) and 2D NMR were used to characterize the structures.
Interesting organic ligand conformational changes may occur
upon complexation of metal ions. One classic example is
the inversion of the chair conformation in cis,cis-1,3,5-
triaminocyclohexane. Upon chair inversion, three equatorial
amine groups in the free ligand become axial to chelate a
metal ion (eq 1). In this paper, we report a ligand containing
coordination numbers in tripodal TQA (tris(2-quinolyl-
5
methyl)amine) complexes. A dynamic NMR study of a
I
methyl-substituted TQA Cu complex proved that one of the
1
three arms is dissociated from metal coordination when the
II
I
Cu ion is reduced to Cu . It also indicated that the steric
effect of the methyl group provides control as to which arm
6
of the ligand will be in motion. Herein, we report a chiral
TQA-based ligand 1 in which a piperidine ring links two of
the quinoline arms. The different coordination number of
(
3) (a) Liu, Y.; Flood, A. H.; Stoddart, J. F. J. Am. Chem. Soc. 2004,
1
26, 9150-9151. (b) Dei, A.; Gatteschi, D.; Sangregorio, C.; Sorace, L.
Acc. Chem. Res. 2004, 37, 827-835. (c) Guo, X.; Zhang, D.; Tao, H.; Zhu,
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Di Bella, S. J. Am. Chem. Soc. 2003, 125, 1122-1123. (e) Akasaka, T.;
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Licchelli, M.; Mascheroni, S.; Poggi, A.; Sacchi, D.; Zema, M. Inorg. Chem.
a six-membered piperidine ring triggered to interconvert
between its two possible chair conformations by one-electron
oxidation or reduction.
We previously described molecular redox switches2,3
driven by the one-electron oxidation or reduction of a copper
2
002, 41, 6129-6136.
(4) (a) Barcena, H. S.; Liu, B.; Mirkin, M. V.; Canary, J. W. Inorg. Chem.
4
2005, 44, 7652-7660. (b) Barcena, H. S.; Holmes, A. E.; Zahn, S.; Canary,
J. W. Org. Lett. 2003, 5, 709-711. (c) Zahn, S.; Canary, J. W. Science
ion. The two states of a copper ion display different
2
000, 288, 1404-1407.
(
1) (a) Lions, F.; Martin, K. V. J. Am. Chem. Soc. 1957, 79, 1572-
(5) (a) Zahn, S.; Canary, J. W. J. Am. Chem. Soc. 2002, 124, 9204-
1
6
575. (b) Wentworth, R. A. D.; Felten, J. J. J. Am. Chem. Soc. 1968, 90,
21-626.
9211. (b) Zahn, S.; Canary, J. W. Angew. Chem., Int. Ed. 1998, 37, 305-
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6093-6100.
(6) Zhang, J.; Siu, K.; Lin, C. L.; Canary J. W. New J. Chem. 2005, 29,
1147-1151.
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M. Chem. ReV. 2000, 100, 1789-1816. (b) Molecular Switches; Feringa,
B. L., Ed.; Wiley-VCH: Weinheim, 2001.
1
0.1021/ol061364k CCC: $33.50
© 2006 American Chemical Society
Published on Web 08/01/2006

II
I
Cu vs Cu provides the driving force for the ligand to adopt
II
a higher energy chair conformation in the Cu complex.
Ligand 1 was constructed by a strategy involving the
formation of a trans-piperidine moiety by tandem S 2
N
substitution reactions from two components: the achiral
primary amine 6 and the chiral dimesylate 10 (Figure 1). In
I
Figure 2. CD spectra of 1 (black), Cu (1)ClO
4
(red) and its
II
oxidative product by air (blue), Cu (1)(ClO
reductive product by ascorbic acid (cyan), and Zn (1)(ClO
4
)
2
(green) and its
II
4 2
)
(magenta) in acetonitrile.
4
-1
-1
to 4.0 × 10 L cm mol ), which is polarized nearly
8
parallel to the longitudinal axis. The through-space exciton
interaction of the quinolines held in proximity by the metal
induces the splitting of the peaks in the CD and UV
spectrum. A bisignated CD couplet and UV peak broadening
II
for the Cu complex are clearly shown in Figure 2, and there
are good correlations between the CD Cotton effects and
UV absorbance maximum and shoulder (239 vs 238 nm, 227
vs 228 nm). The amplitude of this CD spectrum is very large
Figure 1. Synthetic route for ligand 1.
-
1
-1 5
(A ) 1094 L cm mol ). The positive chirality indicated
addition to the desired trans compound (80% yield), a cis
compound was also collected as a byproduct (4% yield). The
de for the products was 95% as determined by H NMR,
and the ee for the trans compound was >99% as determined
by HPLC (chiral column, ChiralCel OJ-H). The stereochem-
istry of 1 was established by the stereoselective reduction
of diketone 8 with (-)-DIP-Cl. The metal complexes were
by ECCD is consistent with the R,R configuration of the
ligand.
Also shown in Figure 2 is that free ligand 1 gave a weaker,
1
-
1
-1
single-peak CD spectrum (∆ꢀ ) +199 L cm mol at 231
4
-1
nm), with UV λmax at 228 nm (ꢀ ) 13.4 × 10 L cm
-
1
I
I
mol ). The Cu complex, Cu (1)(ClO
4
), showed a CD
-1
-1
spectrum (∆ꢀ ) +204 L cm mol at 230 nm) very similar
to that of the free ligand 1 but exhibited a slight negative
prepared in situ by mixing ligand 1 with corresponding
II
perchlorate metal salts. Precipitation [Cu (1)(ClO
4
)
2
] or
-
1
-1
I
II
Cotton effect at about 239 nm (∆ꢀ ) -63 L cm mol ).
solvent evaporation [Cu (1)ClO
4
and Zn (1)(ClO
4
)
2
] offered
-
-
-
Changing the counterion from ClO
4 6
to PF or SCN had
solid samples.
little effect on the shape or intensity of the spectra. The
Exciton-coupled circular dichroism (ECCD) has often been
II
I
7a
dramatic changes in the CD spectra of the Cu and Cu
utilized to study conformational changes. As shown in
II
II
complexes illustrate a remarkable redox-triggered chiroptical
Figure 2, the Cu complex, Cu (1)(ClO
4 2
) , produced a very
5
switch.
strong CD spectrum, with a positive first Cotton effect at
-
1
-1
The “on-off” modulation of the CD signal could be
2
39 nm (∆ꢀ ) +687 L cm mol ) followed by a negative
-
1
-1
achieved using redox reagents. As shown in Figure 2, simply
second Cotton effect at 227 nm (∆ꢀ ) -407 L cm mol ).
I
4
leaving the Cu complex in the air overnight oxidized it to a
The UV λmax in this region is at 228 nm (ꢀ ) 12.3 × 10 L
-
1
-1
4
cm mol ), with a shoulder at 238 nm (ꢀ ) 8.3 × 10 L
(7) (a) Berova, N.; Nakanishi, K.; Woody, R. W. Circular Dichroism:
-1
-1
cm mol ). This spectrum can be assigned to ECCD, which
originates from the spatial arrangement of the three chro-
Principles and Applications, 2nd ed.; Wiley-VCH: New York, 2000. (b)
Zhang, J.; Holmes, A. E.; Sharma, A.; Brooks, N. R.; Rarig, R. S.; Zubieta,
J.; Canary, J. W. Chirality 2003, 15, 180-189.
7
mophores defined by the chiral center. The relevant quino-
(8) Castagnetto, J. M.; Xu, X.; Berova, N.; Canary, J. W. Chirality 1997,
1
4
line transition is the B
b
band (225-227 nm, ꢀ ) 3.5 × 10
9, 616-622.
3908
Org. Lett., Vol. 8, No. 18, 2006

II
Cu complex, exhibiting a CD spectrum similar to that of
arms coordinated). No low-energy conformation was found
in which the quinoline attached to the CH group was
II
the preformed Cu complex. After ascorbic acid was added
to a solution of the Cu complex for 1 h, a spectrum similar
to that of the authentic Cu complex was obtained.
The CD spectral differences must arise from different
orientations of the chromophores that can be accounted for
by analysis of the conformational behavior of the ligand.
2
II
dissociated from the metal. The amplitude of ECCD is
proportional to the angle between the chromophores. The
I
II
projection angle between the quinolines for the Cu complex
I
was +58° and for the Cu complex was -15°. These data
II
are consistent with the ECCD amplitude for the Cu and
II
I
The strong amplitude of the Cu complex indicates that all
Cu complexes.
three arms ligate the metal and offer three pairwise exciton
interactions. To achieve this, the Cu complex must assume
1
H NMR spectroscopy was used to test these structural
II
II
hypotheses. Unable to observe spectra of the Cu complex
due to its paramagnetism, the Zn (ClO
used instead of the Cu (ClO ) complex in the NMR studies.
4 2
The Zn complex of 1 showed an ECCD spectrum similar
to that for the Cu complex, suggesting a similar conforma-
tion.
a C
3
-like symmetry, and the quinoline chromophores must
II
4
)
2
complex of 1 was
I
possess large projection angles with each other. The Cu
complex, on the other hand, must adopt some other structure
that is not apparent from analysis of the CD spectra. Models
II
II
II
I
suggest a possible conformation for the Cu complex with
one arm dissociated from the metal and the other two arms
bound with a small projection angle.
The trans-substitution pattern on the piperidine allows
either two equatorial and one axial substituents or one
equatorial and two axial substituents, and the energy of the
former is lower than that of the latter (Figure 3). However,
There are remarkable differences among the free ligand,
I
II
1
the Cu complex, and the Zn complex in the H NMR
spectra, suggesting different conformations in solution. The
most obvious changes come from the two CH protons next
to the quinolines on the chiral arms and the two CH protons
2
next to the quinoline on the achiral arm. The free ligand has
one multiplet at 4.85 ppm for the two CH protons and AB
2
pattern doublet peaks for the two CH protons at very similar
I
chemical shifts (3.89 and 3.85 ppm). The Cu complex gives
widely separated CH proton peaks (6.03 vs 4.58 ppm) and
2
relatively less-separated CH doublet peaks (4.13 vs 3.77
II
ppm). The Zn complex also has four distinguishable peaks,
but the separation of these two kinds of protons is reversed.
The two CH protons are closer (4.71 vs 4.54 ppm), and the
two CH
ppm). In the Zn complex, the two CH protons and one of
the CH protons are in almost the same chemical shift region
around 4.6 ppm), whereas in the Cu complex, all four
2
protons are more widely separated (4.64 vs 4.07
II
2
I
(
protons are widely separated.
1
Comparison of the H NMR spectra of the free ligand,
I
II
the Cu complex, and the Zn complex supports the confor-
mational model. In the free ligand, the two CH protons
adjacent to the quinolines on the chiral arms are equivalent
as a result of the interconversion of the two chair conforma-
tions, inversion of the nitrogen atom, and bond rotations.
2
The two CH protons next to the quinoline of the achiral
arms are different due to the chiral environment but still close
in chemical shift. Complexation with metals blocks the
inversion of the tertiary nitrogen and differentiates all four
I
II
Figure 3. (a) Conversions between Cu (1) and Cu (1). (b) Free
ligand conformational interconversions that result in exchange of
two of the quinoline moieties.
I
protons. In the Cu complex, the achiral arm and one of the
chiral arms ligate the metal, and the other chiral arm
dissociates and points away from the metal, leaving the two
CH protons in very different chemical environments. The
CH proton of the unbound chiral arm lies in the shielding
region of the quinoline group of the bound achiral arm,
whereas the CH proton of the bound chiral arm is close to
the quinoline on the unbound chiral arm and in its deshielding
coordination of all four nitrogen atoms of the ligand requires
a conformation with two axial substituents. Presumably, Cu
binds very strongly to the ligand and the favorable energy
II
of tetradentate complex formation drives the ligand into a
higher-energy conformation. The free ligand and the CuI
complex, however, assume a lower-energy conformation that
leaves one quinoline moiety remote from the metal ion.
2
region. The two CH protons are also more differentiated.
I
9
The fixed conformation of the Cu complex leaves one proton
Conformer searches using the Spartan program were
II
II
in the more deshielding region than the other. For the Zn
performed to give the lowest-energy conformers for the Cu
I
complex, all three arms are coordinated to the metal, and
the molecule adopts a C -like symmetry. The two CH protons
3
complex (three arms coordinated) and the Cu complex (two
(9) Spartan 5.0; Wavefunction, Inc.: Irvine, CA, 1997.
and one of the CH
2
protons are in a very similar chemical
Org. Lett., Vol. 8, No. 18, 2006
3909

environment and, therefore, locate at the same chemical shift
region in the H NMR spectrum. The other CH proton points
2
quinoline on the unbound chiral arm). However, this H8b is
close to CHa (the CH proton of the quinoline on the bound
1
toward the alkane part of the piperidine ring rather than
toward the aromatic quinoline rings and has a chemical shift
that is more downfield. Compared to the two bound quino-
chiral arm). The two CH
showed an interesting difference. CH
protons) is close to both of the two CH protons (CHa and
CHb), and CHâ (the other CH proton) is only close to one
2
protons on the achiral arm also
2
R (one of these CH
2
I
II
lines of the Cu complex, the three quinolines of the Zn
2
complex are further apart and have less effect on each other.
NOESY NMR spectra were also supportive of the con-
formational model. The NOESY spectrum of the CuI
complex is shown in Figure 4, along with a structural model.
of the CH protons (CHa). All of these NOESY through-
space correlations can be found in the structural model for
I
the Cu complex (Figure 4). In the NOESY spectrum of the
II
Zn complex, the H8 proton of any quinoline is not close to
2
any other H8 proton, and only one of the CH protons of
the achiral arm is close to one of the CH protons of the chiral
arms. There is also no unique through-space interaction
shown between the arms of the free ligand.
Besides the negative signals, useful positive cross-peaks
were shown for the CH protons (CHa with CHb), H3 protons
(H3a with H3b), and H8 protons (H8a with H8b) of the two
chiral arms (Figure 4). This indicates that either of the two
I
quinolines on the chiral arms can bind with the Cu while
I
the other dissociates; therefore, there are two identical Cu
complexes in solution. Each chiral arm may be dissociated
or associated, resulting in an exchange cross-peak in the
NOESY spectrum. This exchange process also explains why
each CH proton (CHa and CHb) showed NOE to the H3
proton of both chiral arms (H3a and H3b). The ROESY
I
spectrum of the Cu complex confirmed the exchange aspects
of the NOESY spectrum.
In conclusion, a new redox-triggered chair conformational
change based on a trans-piperidine rigidified tripodal ligand
I
1
was demonstrated. The Cu complex of ligand 1 showed
II
an induced CD or weak ECCD spectrum, whereas the Cu
complex showed a very strong ECCD spectrum. The
switching of the circular dichroic signal was caused by the
1
conformational change of the ligand. As indicated by H
NMR and NOESY spectra and computation, only one arm
I
in the Cu complex occupies the axial position, along with
II
the other achiral arm, to coordinate to the metal. In the Cu
complex, two arms adopt the axial position and all three arms
ligate the metal. Besides potential application as redox-
triggered materials such as optical displays or molecular
electronics, this well-defined Cu(I/II) redox couple may also
be of interest with respect to redox active metalloenzymes
Figure 4. NOESY spectrum (in CD
3
CN) and structural model of
I
Cu (1)ClO
4
. The cross-peaks shown in cyan frames indicate
1
1
through-space interaction between arms, and the cross-peaks shown
in blue frames indicate exchange between the arms. The structural
model was calculated using the semiempirical method PM3(tm).
and catalysts.
Acknowledgment. This work was supported by the
National Science Foundation (CHE-0316589 to J.C. and
instrument grants CHE-0116222 and CHE-0234863). We are
grateful to Dr. Chin Lin, Kam Siu, and Sutang Cai (NYU)
for their helpful participation in this project. We acknowledge
the NCRR/NIH for a Research Facilities Improvement Grant
(C06RR-16572).
In this NOESY spectrum, the negative cross-peaks (shown
in black) indicate the through-space NOE correlations, and
the positive cross-peaks (shown in red) indicate exchange
processes.10 There are five cross-peaks that indicate unique
through-space correlations between the arms for the CuI
complex. Hydrogen 8a (the H8 proton of the quinoline on
the bound chiral arm) is close to H8c (the H8 proton of the
quinoline on the bound achiral arm), but neither of these
two H8 protons is close to H8b (the H8 proton of the
Supporting Information Available: Experimental details
I
II
and spectroscopic data of 1 and various Cu (1) and Cu (1)
complexes. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL061364K
(
10) Lambert, J. B.; Shurvell, H. F.; Lightner, D. A.; Cooks, R. G.
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669-683. (b) Rorabacher, D. B. Chem. ReV. 2004, 104, 651-697. (c)
Blackman, A. G. Polyhedron 2005, 24, 1-39.
Organic Structural Spectroscopy; Prentice-Hall: Upper Saddle River, New
Jersey, 1998.
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Org. Lett., Vol. 8, No. 18, 2006