quite rare, but of significant importance in functional crystal
engineering and supramolecular chemistry.10
Another example, reported by Duda et al., is even more
significant as it supports our conclusion about key effect of
the steric bulk as well as possibility to generate supramo-
lecular helicity in the solid state without the molecular
chirality in the starting compounds.12 Thus, amides 6a and
6b (Figure 6), derived from acetic and p-(methyl)benzoic
acids, respectively, gave achiral, parallel arrangement of
hydrogen bonded molecules. On the other hand, compound
6c, containing a sterically demanding tert-butyl group,
generated supramolecular helicity in the solid state.
With these results in hand, we decided to further inves-
tigate importance of the steric factor of a tert-butyl group.
Therefore the effect of a gradual reduction of the steric bulk
of a tert-butyl group on the supramolecular structure in the
solid state was studied. To this end we prepared the
corresponding amide 4 (Figure 4), derived from benzylamine
and 2-(methyl)propionic acid, containing less sterically bulky
iso-propyl group instead of tert-butyl group. The result of
the X-ray analysis of the amide 4 was quite conclusive. The
molecular structure of derivative 4 was found to be achiral,
as molecules of less sterically demanded iso-propyl contain-
ing 4 found the way of packing in more compact parallel
arrangement.
Figure 6. Literature example of helical structure in the solid state
of pivalic acid derived amide lacking molecular chirality.
Furthermore, the detailed analysis of the available crystal-
lographic data clearly pointed out the importance of the
formation of an uninterrupted, infinite hydrogen-bonding
network between the molecules, providing the corresponding
axis for the helical arrangement of sterically bulky groups
around it. For instance, in the case of compounds containing,
besides the tert-butyl group, multiple functionalities such as
hydroxy, free carboxy, or amino groups, which interfere with
the formation of proper one-dimensional hydrogen bonding
network, the corresponding helical structure in the solid state
was not observed.13 A similar result was found for tert-butyl-
containing compounds that cocrystallize with molecules of
protic solvent such as water or alcohol. Upon being
incorporated into the crystallographic structure, these hydroxy
group containing molecules interfere with the formation of
the proper hydrogen bonding network and obstruct the
realization of the sterically driven helical structure.14The
importance of the formation of a proper hydrogen-bonding
network is, probably, most clearly manifested from the
crystallographic structures of pivaloyl amides prepared from
secondary amines, which cannot form the required hydrogen
bonding network and therefore the corresponding macro-
molecular helicity in the solid state.15
Figure 4. Molecular and crystallographic structure of amide 4.
These results clearly demonstrated a key importance of
the presence of a tert-butyl group in the starting compound
for generation of helical chirality in the solid state.
Finally, we were delighted to find that available literature
data are in full accord with our results and therefore provide
an additional support of our hypothesis of a new sterically
driven mode for generation of helical chirality in the solid
state. Thus, Lait et al. reported synthesis and crystallographic
structure of pivalic acid derived amides 5a and 5b (Figure
5).11 Both compounds 5a and 5b showed exclusively (M)-
helical arrangements along the hydrogen-bonding axis of the
amide functionality. Since the compounds 5a and 5b contain
multiple stereogenic centers, it is not possible to rationalize
the effect of their absolute configuration on the sense of the
generated helical chirality.
(10) (a) Metrangolo, P.; Meyer, F.; Pilati, T.; Resnati, G.; Terraneo, G.
Angew. Chem., Int. Ed. 2008, 47, 6114–6127. (b) Desiraju, G. R. Angew.
Chem., Int. Ed. 2007, 46, 8342–8356. (c) Zaworotko, M. J. Angew. Chem.,
Int. Ed. 1998, 37, 1211–1213.
(11) Lait, S. M.; Parvez, M.; Keay, B. A. Tetrahedron: Asymmetry 2003,
14, 749–756.
(12) Duda, L.; Erker, G.; Fro¨hlich, R.; Zippel, F. Eur. J. Inorg. Chem.
1998, 1153–1162.
(13) For example:(a) Ananda, K.; Aravinda, S.; Vasudev, P. G.; Raja,
K. M. P.; Sivaramakrishnan, H.; Nagarajan, K.; Shamala, N.; Balaram, P.
Curr. Sci. 2003, 85, 1002. (b) Belokon, Y. N.; Bespalova, N. B.; Churkina,
T. D.; Cisarova, I.; Ezernitskaya, M. G.; Harutyunyan, S. R.; Hrdina, R.;
Kagan, H. B.; Kocovsky, K. A.; Kochetkov, K. A.; Larionov, O. V.;
Lyssenko, K. A.; North, M.; Polasek, M.; Peregudov, A. S.; Prisyazhnyuk,
V. V.; Vyskocil, S. J. Am. Chem. Soc. 2003, 125, 12860. (c) Das, A. K.;
Bose, P. P.; Drew, M. G. B.; Banerjee, A. Tetrahedron 2007, 63, 7432.
Figure 5. Literature example of helical structure in the solid state
of pivalic acid derived amide containing molecular chirality.
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