trans-cyclohexane-1,2-diamine is a weak director of absolute helicity in chiral nickel-salen complexes

Article abstract of DOI:10.1021/ja073900p

The interconversion between helical diastereomers of nickel-salen-based foldamers can be observed on a NMR time scale. Such complexes provide quantitative information about the propensity of different elements of central chirality to control the absolute

Full text of DOI:10.1021/ja073900p

Published on Web 08/31/2007
trans-Cyclohexane-1,2-diamine Is a Weak Director of Absolute
Helicity in Chiral Nickel-Salen Complexes
Zhenzhen Dong, Glenn P. A. Yap, and Joseph M. Fox*
Contribution from the Brown Laboratories, Department of Chemistry and Biochemistry,
UniVersity of Delaware, Newark, Delaware 19716
Received May 30, 2007; E-mail: jmfox@udel.edu
Abstract: The interconversion between helical diastereomers of nickel-salen-based foldamers can be
observed on a NMR time scale. Such complexes provide quantitative information about the propensity of
different elements of central chirality to control the absolute sense of folding. trans-Cyclohexane-1,2-
diaminesa common component of chiral salen catalystssis a surprisingly weak director of absolute helicity
in nickel-salen foldamers. Implications for asymmetric catalysis are discussed.
Introduction
Chiral salens are exceptionally useful ligands for asymmetric
catalysis,1 and the origin of asymmetric induction in reactions
catalyzed by chiral metal-salen complexes has been a topic of
considerable interest.2-5 Many models for asymmetric induction
by salen-metal catalysts have focused on the role of central
chirality, in which stereogenic centers within the catalyst
backbone directly influence the approach of a substrate to one
enantiotopic face of the catalyst.2 However, central chirality can
also induce helicity in salen-metal complexes, and in some
models for asymmetric induction, it has been argued that
helical6,7 chirality plays a critical role in asymmetric catalysis.3-5
For example, elegant studies by Katsuki have demonstrated
that chiral donor ligands can induce a high enantioselectivity
inepoxidationscatalyzedbyachiralmanganese-salencatalysts.1b,c,3c
Computational studies on the manganese-salen catalyzed
epoxidation have also connected asymmetric induction to
folding of the salen ligand.5 More recently, Rawal and co-
workers hypothesized that helicity plays a role in cobalt-salen
catalyzed asymmetric Diels-Alder reactions, and this hypo-
thesis guided the design of a more effective generation of
catalysts.4
Figure 1. Mismatched chirality in metallofoldamers as a probe for helical
bias.
Implicit to models that invoke helicity to explain asymmetric
induction is that an element of central chirality (typically a chiral
diamine) creates a bias for one sense of folding in metal-salen
complexes. However, two helical diastereomers are possible for
metal-salens derived from chiral diamines. Under catalytic
conditions, it is possible that these diastereomers would
equilibrate and that Curtin-Hammett kinetics would be relevant.
Currently, tools for directly measuring such ratios of helical
diastereomers are lacking. We hypothesized that ratios of helical
diastereomers could be measured by juxtaposing different
elements of chirality within salen complexes that are predisposed
to fold (Figure 1). In this scenario, the chiral end-group (R*)
would bias for the formation of a (M)-helix, whereas the diamine
would bias for the diastereomeric metallofoldamer of (P)-
helicity. Spectroscopic and crystallographic studies of such
complexes would provide a measure of the ability of the chiral
diamine to control helicity relative to the end-group.
(1) (a) Larrow, J. F.; Jacobsen, E. N. Top. Organomet. Chem. 2004, 4, 123.
(b) Katsuki, T. AdV. Synth. Catal. 2002, 344, 131. (c) Katsuki, T. Synlett
2003, 281.
(2) (a) Jacobsen, E. N.; Zhang, W.; Muci, A. R.; Ecker, J. R.; Deng, L. J. Am.
Chem. Soc. 1991, 113, 7063. (b) Zhang, W.; Loebach, J. L.; Wilson, S. R.;
Jacobsen, E. N. J. Am. Chem. Soc. 1990, 112, 2801.
Previously, we described helical nickel-salophens 1 and 2,
in which absolute helicity is determined by chiral end-groups
A and B (Figure 2).8,9 For 1, two conformers of opposite helicity
interconvert on the NMR time scale with a slight (∼2:1) bias
for the (M)-helix over the (P)-helix. By contrast, 2 is dominated
by an (M)-helix that is stabilized by 3-point hydrogen bonds.
(3) (a) Katsuki, T. J. Mol. Catal. A: Chem. 1996, 113, 87. (b) Hamada, T.;
Fukuda, T.; Imanishi, H.; Katsuki, T. Tetrahedron 1996, 52, 515. (c)
Hashihayata, T.; Ito, Y.; Katsuki, T. Tetrahedron 1997, 53, 9541. (d)
Noguchia, Y.; Irie, R.; Fukuda, T.; Katsuki, T. Tetrahedron Lett. 1996,
37, 4533. (e) Ito, Y. N.; Katsuki, T. Tetrahedron Lett. 1998, 39, 4325.
(4) (a) Huang, Y.; Iwama, T.; Rawal, V. H. J. Am. Chem. Soc. 2002, 124,
5950. (b) McGilvra, J. D.; Rawal, V. H. Synlett 2004, 2440.
(5) Jacobsen, H.; Cavallo, L. Chem.sEur. J. 2001, 7, 800.
(6) We consider chiral stepped conformations1 of salens to be encompassed
within the definition of helical chirality.
(7) It has been demonstrated that multiple elements of chirality can work
synergistically to induce asymmetry in metal-salen catalyzed transforma-
tions. See ref 1b,c and (a) Walsh, P. J.; Lurain, A. E.; Balsells, J. Chem.
ReV. 2003, 103, 3297. (b) DiMauro, E. F.; Kozlowski, M. C. Org. Lett.
2001, 3, 1641.
(8) (a) Zhang, F.; Bai, S.; Yap, G. P. A.; Tarwade, V.; Fox, J. M. J. Am. Chem.
Soc. 2005, 127, 10590. (b) Dong, Z.; Karpowicz, R. J., Jr.; Bai, S.; Yap,
G. P. A.; Fox, J. M. J. Am. Chem. Soc. 2006, 128, 14242.
(9) For salen-based foldamers, see footnotes in ref 8 and Akine, S.; Taniguchi,
T.; Nabeshima, T. J. Am. Chem. Soc. 2006, 128, 15765.
9
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trans-Cyclohexane-1,2-diamine Is Weak Director of Helicity
A R T I C L E S
Scheme 2. Chiroptical Data and X-ray Crystal Structures for 4
and 5 Show That Absolute Sense of Helicity Is Determined by the
End-Group and Not the Diaminea
Figure 2. End-group directors of absolute helicity in salophen foldamers.
Scheme 1
a Displayed CD spectra are those from CH2Cl2 solutions of 4 (3.6 ×
10-4 M) and 5 (3.6 × 10-4 M). C12H25 side chains are not displayed in the
X-ray structures.
Results and Discussion
To measure the ability of trans-cyclohexanediamine to control
absolute helicity, salens 4 and 5 were prepared from salicyla-
ldehyde 38b using the ozonolysis approach8a outlined in Scheme
1. This synthetic approach, which parallels our earlier approach
to foldamer 2,8b takes advantage of Pd catalyzed C-O bond
formation10 and the differential reactivity of the amino groups
of dodecyl-2,3-diaminobenzoate toward acylhalides.
Spectroscopic and X-ray crystallographic properties of 4 and
5 are displayed in Scheme 2. In 4, the helical bias of the diamine
is matched to that of the end-group B. As expected, the
chiroptical properties of 4 indicate the formation of an (M)-
helix: a strong, negative CD signal and a large specific rotation
([R]D -1200°) were observed. In 5, the chirality of the diamine
and the end-group are mismatched: the diamine biases for a
(P)-helix, whereas the end-group biases for an (M)-helix.
Strikingly, the chiroptical data indicate that the end-group
completely overrides the diamine. Thus, the specific rotation
(-950°) and the magnitude and shape of the CD spectrum are
similar to those of 4 and are indicative of (M)-helicity. CD
spectroscopy also indicates that the folding of 4 and 5 is not
disrupted by the addition of MeOH. Thus, the spectra of 4 and
5 in 1:1 MeOH/CH2Cl2 (displayed in the Supporting Informa-
tion) were nearly identical to those displayed in Scheme 2.
Thus, end-group B can be considered to be a strong director of
absolute helicity in salophen foldamers, whereas end-group A
provides only a weak bias.
Herein, it is demonstrated that trans-cyclohexane-1,2-diamines
a common component of chiral salen catalystssis a surprisingly
weak director of absolute helicity in nickel-salen metallofol-
damers. This is demonstrated not only for foldamers that contain
competing elements of chirality (as depicted in Figure 1) but
also for a foldamer in which the diamine is the only element of
central chirality. For models that invoke helicity to explain
asymmetric induction by metal-salen catalysts, an implication
is that both helical diastereomers are viable.
(10) Palucki, M.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118,
10333.
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A R T I C L E S
Dong et al.
Figure 3. Comparison of 1H NMR chemical shifts of 4 and 5 against
salicylaldehyde precursor 3. The ∆δ values refer to upfield chemical shifts
relative to 3. Large chemical shift anisotropies were also observed for
foldamers 6-8.
Scheme 3. Chiroptical Data for 6 and 7a
Figure 4. VT-NMR spectra of 5-7 (CDCl3).
small. Thus, the chiroptical data suggest only a modest
preference for the (P)-helix in 7.
a CD spectra are those from CH2Cl2 solutions of 6 (3.8 × 10-4 M) and
7 (3.8 × 10-4 M).
VT-NMR also suggests that 7 is a mixture of conformers. In
previous VT-NMR studies on 1, a chemical exchange with
coalescence at -25 °C was assigned to the equilibrium between
two diastereomers of opposing helicity as shown in Figure 2.
For 7, a chemical exchange occurs with a similar coalescence
temperature (Figure 4). Two conformers are detected in a 3:2
ratio. By contrast, chemical exchange is not observed in this
temperature range for 5 and 6. We propose that the two
conformers of 7 are diastereomers of opposite helicity.
CD spectroscopy also supports that the diminished chiroptical
properties of 7 result from a mixture of two helical diastereomers
and not from unfolding of the helix. Only very minor differences
in the CD spectra of 7 are noted upon changing the solvent
from CH2Cl2 to DMSO (Figure 5). Furthermore, the CD
spectrum of 7 in DMSO is nearly super superimposable with
the spectrum recorded in 10:1 DMSO/H2O (7 precipitated from
DMSO containing higher proportions of water). These data
suggest that the helical structures are conserved across solvents
with dramatically different abilities to disrupt hydrogen bonding.
The studies on 4-7 suggested that it would be possible to
detect helical diastereomers for foldamers in which (R,R)-
cyclohexanediamine is the only element of central chirality. To
test this hypothesis, we synthesized Ni complex 8san analogue
The X-ray crystal structures of 4 and 5 were also determined
(Scheme 1). Both structures are helical with an (M)-configu-
ration. The structures are highly analogous and resemble those
determined previously for 2. In accord with the conclusion of
chiroptical studies in solution, the absolute configuration of 5
is governed by the end-group and not by the diamine.
Chemical shift anisotropies in the 1H NMR spectra of 4 and
5 also support that their structures are helical (Figure 3). In
previous studies on salophen 2, significant upfield chemical
shifts were associated with the aliphatic hydrogens of the
dihydrobenzofuran ring.8b Upfield chemical shifts of similar
magnitudes were observed for salens 4 and 5 as compared to
their salicylaldehyde precursor 3.
Using procedures that mirrored those in Scheme 1, salen
compounds 6 and 7 were prepared. These salen complexes also
combined elements of chirality from trans-cyclohexanediamine
and end-group A, a weak director of absolute helicity (vide
supra) (Scheme 3). Chemical shift anisotropies suggest that both
6 and 7 have helical structures (see Supporting Information).
As expected, the chiroptical data indicate a strong bias for the
(M)-helix in 6 ([R]D -1100°) as the chirality of the end-group
is matched to that of the diamine. In the mismatched 7, the
positive dichroisms in the CD spectrum indicate a reversal in
helicity. However, the peaks in the CD of 7 are only ∼30% as
intense of those of 4-6, and the rotation ([R]D +73°) of 7 is
1
of 4 with achiral end-groups (Scheme 4). H NMR chemical
shift anisotropy (Supporting Information) and NOESY studies
suggest that 8 is helical. The trans-helix internuclear distances
that were measured to be less than 4.5 Å by NOE are displayed
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trans-Cyclohexane-1,2-diamine Is Weak Director of Helicity
A R T I C L E S
Figure 5. CD spectra of 7 in DMSO (7.7 × 10-4 M) and in 10:1 DMSO/
H2O (7.0 × 10-4 M).
Scheme 4. Salen 8 Is an Equilibrating Mixture of Helical
Diastereomersa
Figure 6. Selected NOE signals that were observed for 8.
consistent with prior NOESY studies on 28b and provide strong
support that 8 is helical in solution.
While NMR studies suggest that 8 is helical, the CD and
specific rotation ([R]D -140°) of 8 are weak (Scheme 4). In
the VT-NMR spectrum, coalescence is observed at -10 °C.
Our interpretation of this data is that two diastereomers [8(M)
and 8(P)] are in equilibrium, with only a slight (5:4) bias for
the M-helix.
Conclusion
Salen-based metallofoldamers are useful tools for studying
the influence of central chirality on the absolute sense of helical
induction, as the interconversion between helical diastereomers
can be observed on the NMR time scale. End-group chirality
can dominate the sense of absolute helicity in nickel-salen
derivatives that are predisposed to fold into helices. However,
it is concluded that trans-cyclohexanediamine is only a weak
director of absolute helicity in similar foldamers. Both helical
diastereomers should be considered in any models that invoke
helicity to explain asymmetric induction with chiral salens.
a 1H NMR spectra were measured in CDCl3, and CD spectrum was
Acknowledgment. This work was supported by the NSF
CAREER Award CHE-0547865. Questions regarding the X-rays
should be addressed to G.P.A.Y. (gpyap@chem.udel.edu).
measured in CH2Cl2 (2.0 × 10-4 M).
Supporting Information Available: Experimental and char-
acterization details and 1H and 13C NMR spectra for new
compounds. CD spectra, UV-vis spectra, and chemical shift
anisotropy data for 4-8 and NOE data for 8. CIF files for 4
and 5. This material is available free of charge via the Internet
at http://pubs.acs.org.
in Figure 6. In particular, short internuclear distances were
measured between the cyclohexanediamine methine hydrogens
(H-25) and hydrogens on the terminal anisoyl ring (3.4 and 3.3
Å for H-3 and H-4, respectively). Short distances were also
measured between the hydrogens of the terminal methoxy
groups (H-1) and the underlying aromatic ring (3.4, 3.3, and
3.9 Å for H-19, H-20, and H-21, respectively). These data are
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