C O M M U N I C A T I O N S
The NOESY spectrum of 5 provided further evidence that 5(M)
is a significant conformation in solution. The trans-helix internuclear
distances that were measured to be less than 4 Å by NOE are
displayed in Figure 5c, along with the analogous distances as
measured by X-ray diffraction. A close correlation between the
X-ray and NOE measurements was observed for 7 of the 9
internuclear distances, including three very close (<3 Å) measure-
ments between the terminus and the core of the helix. For the last
two entries in Figure 5c, the distances measured by NOE were
shorter than those measured by X-ray diffraction. In the context of
the VT-NMR data, it seems likely that these peaks arise from
another conformation that is in equilbrium with 5(M). As an NOE
was not observed between H8 and H12, it is unlikely that this
conformer is 5(P). Crystalline 1 is isostructural to 5(P), and the
analogous distance in 1 was measured to be <4 Å both by X-ray
diffraction and by NOESY. At this time, we cannot estimate the
percentage of conformer 5(M), but given the large chemical shift
anisotropy and significant chiroptical properties, it can be reasoned
either that 5(M) is the major conformation in solution or that the
undetermined conformer also has M-helicity.
Figure 3. Synthesis and chiroptical properties of foldamer 5.
In summary, peripheral stereocenters effectively control the
absolute sense of helicity in Ni-salophen derived foldamers. Future
studies will examine the applications of metallofoldamers in
asymmetric catalysis and materials science.
Acknowledgment. This work was supported by NSF CAREER
Award CHE-0547865. R.J.K. thanks Pfizer for a summer fellow-
ship.
Supporting Information Available: Full experimental details,
1H,13C, and VT-NMR spectra, and cif files. This material is available
Figure 4. Molecular diagrams of 5 from crystallographic coordinates.
References
(1) Reviews and lead references to abiotic, single stranded foldamers: (a)
Hill, D. J.; Mio, M. J.; Prince, R. B.; Hughes, T. S.; Moore, J. S. Chem.
ReV. 2001, 101, 3893. (b) Gellman, S. H. Acc. Chem. Res. 1998, 31, 173.
(c) Moore, J. S. Acc. Chem. Res. 1997, 30, 402. (c) Dolain, C.; Jiang, H.;
Le´ger, J.-M.; Guionneau, P.; Huc, I. J. Am. Chem. Soc. 2005, 127, 12943.
(d) Gong, B. Chem.-Eur. J. 2001, 7, 4336. (e) Zych, A. J.; Iverson, B.
L. J. Am. Chem. Soc. 2000, 122, 8898. (f) Hamuro, Y.; Geib, S. J.;
Hamilton, A. D. J. Am. Chem. Soc. 1997, 119, 10587. (g) Berl, V.; Huc,
I.; Khoury, R. G.; Lehn, J. M. Chem.sEur. J. 2001, 7, 2798.
(2) Borovik, A. S. Acc. Chem. Res. 2005, 38, 54.
(3) For examples in which metal coordination nucleates an abiotic, single
stranded foldamer: (a) Zhang, F.; Bai, S.; Yap, G. P. A.; Tarwade, V.;
Fox, J. M. J. Am. Chem. Soc. 2005, 127, 10590. (b) Prince, R. B.; Okada,
T.; Moore, J. S. Angew. Chem., Int. Ed. 1999, 38, 233. (c) Kim, H.-J.;
Zin, W.-C.; Lee, M. J. Am. Chem. Soc. 2004, 126, 7009-7014. (d) Zhao,
Y.; Zhong, Z. J. Am. Chem. Soc. 2006, 128, 9988. For single stranded
foldamers that are templated by metals, see footnote 13 in ref 3a and (e)
Yagi, S.; Morinaga, T.; Nomura, T.; Takagishi, T.; Mizutani, T.; Kitagawa,
S.; Ogoshi, H. J. Org. Chem. 2001, 66, 3848.
(4) Lead examples of abiotic foldamers where absolute helicity is controlled
by stereocenters at the termini, see refs 1c and 3e and (a) Mamula, O.;
von Zelewsky, A. Coord. Chem. ReV. 2003, 242, 87. (b) Baum, G.;
Constable, E. C.; Fenske, D.; Housecroft, C. E.; Kulke, T.; Neuburger,
M.; Zehnder, M. J. Chem. Soc., Dalton Trans. 2000, 945. For examples
of chiral templating: (c) Gin, M. S.; Yokazawa, T.; Prince, R. B.; Moore,
J. S. J. Am. Chem. Soc. 1999, 121, 2643. (d) Woods, C. R.; Benaglia, M.;
Cozzi, F.; Siegel, J. S. Angew. Chem., Int. Ed. Engl. 1996, 35, 1830. (e)
Ali, A. A.-S.; Cameron, K. S.; Cameron, S.; Robertson, K. N.; Thompson,
A. Org. Lett. 2005, 7, 4773. For an example of helical folding through
molecular recognition, see (f) Tanatani, A.; Mio, M. J.; Moore, J. S. J.
Am. Chem. Soc. 2001, 123, 1792. For control over absolute chirality in
helical polymers, see (g) Greene, M. M.; Park, J.-W.; Sato, T.; Teramoto,
A.; Lifson, S.; Selinger, R. L. B.; Selinger, J. V. Angew. Chem., Int. Ed.
Engl. 1999, 38, 3138.
(5) For seminal studies in controlling the absolute helicity of helicene
photocyclizations, see (a) Sudhakar, A.; Katz T. J. J. Am. Chem. Soc.
1986, 108, 179. (b) Katz, T. J.; Sudhakar, A.; Teasley, M. F.; Gilbert, A.
M.; Geiger, W. E.; Robben, M. P.; Wuensch, M.; Ward, M. D. J. Am.
Chem. Soc. 1993, 115, 3182.
(6) For an overview and excellent example of 3-center hydrogen bonding in
foldamer design, see Yuan, L.; Sanford, A. R.; Feng, W.; Zhang, A.; Zhu,
J.; Zeng, H.; Yamato, K.; Li, M.; Ferguson, J. S.; Gong, B. J. Org. Chem.
2005, 70, 10660.
Figure 5. (a) Upfield chemical shifts in 5, as compared to its salicyladehyde
precursor; (b) VT-NMR spectra of 5; (c) the internuclear distances of Ni-
complex 5 from NOESY and X-ray crystallography.
salicylaldehyde precursor, substantial shifts to higher field are
observed for all of the hydrogens highlighted in Figure 5a. The
largest ∆δ is observed for H4, which is positioned directly above
(∼2.7 Å) an aromatic ring in the crystal structure. VT-NMR was
also used to study 5. Whereas all of the aromatic resonances of 4
1
coalesce at -25 °C or above, the H NMR spectrum of 5 is only
slightly broadened at -20 °C (Figure 5b). Although further
broadening is observed with cooling, none of the resonances
coalesced even at -70 °C. While this broadening indicates a
conformational equilibrium for 5, it is unlikely that the equilibrium
involves conformer 5(P), as the new hydrogen bonding interaction
in 5 (Figure 2) should only raise the barrier to helix inversion.
JA065721Y
9
J. AM. CHEM. SOC. VOL. 128, NO. 44, 2006 14243