Enhanced Diastereoselectivity via Confinement
F IGURE 4. Qualitative representations of cation binding to cis-3 (para derivative) within the supercage of a Y zeolite: (A) the
anti conformer within a single supercage; (B) the anti conformer between two supercages.
zeolites might be due to a combination of “tight fit”7 and
maximum “cooperative interaction”8-10 between the cat-
ion, chiral auxiliary, and the reaction site. In the ex-
amples provided in Table 1 diasteroselectivity within RbY
and CsY is small. These large cations probably do not
leave enough room for the meta derivatives to adopt the
anti conformation. As shown in Figure 4, substitution at
the para position probably forces the molecule (anti
conformer) to spread between two supercages. In this
arrangement the interaction between the chiral auxiliary
and the reaction site is expected to be small. Observed
low diastereoselectivity with para isomers is consistent
with this qualitative model.
To gain an insight into the cation controlled diaste-
reoselectivity, ab initio and density functional theory
calculations were carried out on cis-1 and cis-3.11 We
utilize the results of gas-phase computations (RB3LYP/
6-31G*) to understand the behavior within a zeolite.
While one may question the value of gas-phase compu-
tational data in understanding the chemical behavior of
molecules within a zeolite, a much more complex envi-
ronment,12 we find them useful as a guide in building a
preliminary model. The most stable Li+-cis-1 and Li+-
cis-3 structures are shown in Figures 5 and 6. Binding
affinities of Li+ and Na+ ions to cis-1 and cis-3 are fairly
high. The most striking result is that in the case of meta
derivative (anti conformation) the alkali ion interacts
with the chiral auxiliary as well as with one of the two
phenyls of the diphenylcyclopropane (Figure 5). In this
structure (anti conformation) the chiral auxiliary is
brought closer to the reaction site by the alkali ion. In
the syn conformation the cation binds only to the amide
carbonyl and adopts a linear conformation that is larger
than the supercage dimensions. In this structure the
chiral auxiliary is not close to the reaction site. Therefore
the syn conformation is not likely to be important during
diastereoselective photoisomerization within zeolites. As
shown in Figure 6, in the case of the para isomer the
cation-bound structure (anti conformation) is much longer
(18.0 Å) than the width of a supercage.12 Importantly, in
this structure the cation binds only to the chiral auxiliary
and the reaction site is far from the chiral auxiliary.
Therefore one would expect that the influence of a chiral
auxiliary on the isomerization in para derivatives to be
smaller than in corresponding meta derivatives. Experi-
mental results are consistent with this expectation (Table
1). In summary, photoisomerization of 2,3-diphenyl-1-
benzoylcyclopropane derivatives provided an opportunity
to place the chiral perturber at two positions on the
benzoyl part (para and meta), opening up opportunities
to examine the distance dependence of diastereoselectiv-
ity. Clearly, in this system the closer the chiral auxiliary
to the reaction site the more effective it is.
(6) (a) Wiberg, K. B.; Rush, D. J . J . Org. Chem. 2002, 67, 826-830.
(b) Wiberg, K. B.; Rush, D. J . J . Am. Chem. Soc. 2001, 123, 2038-
2046. (c) Wiberg, K. B.; Rablen, P. R.; Rush, D. J .; Keith, T. A. J . Am.
Chem. Soc. 1995, 117, 4261-4270. (d) LeMaster, C. B.; True, N. S. J .
Phys. Chem. 1989, 93, 1307-1311. (e) Ross, B. D.; True, N. S. J . Am.
Chem. Soc. 1984, 106, 2451-2452. (f) Alema´n, C. J . Phys. Chem. A
2002, 106, 1441-1449 and references therein.
(7) Ramamurthy, V. In Photochemistry in Organized and Con-
strained Media; Ramamurthy, V., Ed.; VCH: New York, 1991; p 429.
(8) Ma, J . C.; Dougherty, D. A. Chem. Rev. 1997, 97, 1303-1324.
(9) Raber, D. J .; Raber, N. K.; Chandrasekhar, J .; Schleyer, P. v. R.
Inorg. Chem. 1984, 23, 4076.
(10) (a) Dunbar, R. C. J . Phys. Chem. A 2000, 104, 8067-8074. (b)
Siu, F. M.; Ma, N. L.; Tsang, C. W. J . Am. Chem. Soc. 2001, 123, 3397-
3398. (c) J ockusch, R. A.; Lemoff, A. S.; Williams, E. R. J . Am. Chem.
Soc. 2001, 123, 12255-12265. (d) Wyttenbach, T.; Witt, M.; Bowers,
M. T. J . Am. Chem. Soc. 2000, 122, 3458-3464. (e) J ockusch, R. A.;
Price, W. D.; Williams, E. R. J . Phys. Chem. A 1999, 103, 9266-9274.
(f) Hoyau, S.; Ohanessian, G. Chem. Eur. J . 1998, 4, 1561-1569.
(11) Frisch, M. J . et al. Gaussian 98, Revision A.9; Gaussian, Inc.:
Pittsburgh, PA, 1998.
(12) (a) Breck, D. W. Zeolite Molecular Sieves, Structure, Chemistry
and Use; J ohn Wiley & Sons: New York, 1974. (b) Dyer, A. An
Introduction to Zeolite Molecular Sieves; J ohn Wiley & Sons: New
York, 1988.
As per the results obtained with optically pure trans-
2,3-diphenyl-1-benzoyl-cyclopropane, the triplet diradi-
cals resulting from cleavage of C1-C2 or C1-C3 bonds do
not equilibrate prior to ring closure (Scheme 4). Since
the photoisomerization occurs from the triplet state
zwitterionic intermediates are not likely to be important
both in solution and within zeolites. The stereodifferen-
tiation must occur at the cleavage (and/or reclosure) stage
(C1-C2 vs C1-C3), i.e., the rates of the two cleavages (and/
or reclosure) in the excited state must be different. In
solution, even in the presence of a chiral auxiliary, the
two rates appear to be nearly the same (de 5%). On the
other hand, R-methyl benzyl amide present at the meta
position is able to significantly influence the rates of C1-
C2 and C1-C3 cleavages (and closure) (de 71%). In Figure
5 two structures for Li+-bound cis-1 are shown. Nature
of binding is the same in both cases: the alkali ion binds
to the amide carbonyl, phenyl group of the chiral auxil-
J . Org. Chem, Vol. 69, No. 17, 2004 5533