Confined space and cations enhance the power of a chiral auxiliary: Photochemistry of 1,2-diphenylcyclopropane derivatives

Article abstract of DOI:10.1039/b200640e

Alkali ion-exchanged Y-zeolites significantly enhance asymmetric induction in the photoisomerization of a number of cis-1,2-diphenylcyclopropane derivatives containing a distant chiral auxiliary.

Full text of DOI:10.1039/b200640e

Confined space and cations enhance the power of a chiral auxiliary:
photochemistry of 1,2-diphenylcyclopropane derivatives†
J. Sivaguru,a John R. Scheffer,b J. Chandarasekharc and V. Ramamurthy*a
a Department of Chemistry, Tulane University, New Orleans, LA 70118, USA. E-mail: murthy@tulane.edu
b Department of Chemistry, University of British Columbia, Vancouver V6T 1Z1, Canada
c
Department of Chemistry, Yale University, New Haven CT 06520, USA
Received (in Cambridge, UK) 21st January 2002, Accepted 5th March 2002
First published as an Advance Article on the web 20th March 2002
Alkali ion-exchanged Y-zeolites significantly enhance asym-
metric induction in the photoisomerization of a number of
cis-1,2-diphenylcyclopropane derivatives containing a dis-
tant chiral auxiliary.
parent system, such is not the case for the amide derivative. This
key observation permitted us to investigate asymmetric induc-
tion during the isomerization of optically pure amides of 2b,3b-
diphenylcyclopropane-1a-carboxamide to the trans form. The
distal amide substituent serves as the chiral auxiliary. Upon
excitation of these amides, the C2–C3 bond cleaves resulting in
free rotation of the C1–C2 and/or C1–C3 bond. The absolute
configuration of the final product depends on which of these
two bonds rotates (Scheme 1).
In this communication, we report the results on eleven chiral
amides of 2b,3b-diphenylcyclopropane-1a-carboxylic acid
(Scheme 1). When the amides 1a–k were irradiated in hexane–
methylene chloride solution the corresponding trans isomers
The unique nature of organized media is nowhere more evident
than in their ability to control the formation of enantiomerically
enriched photoproducts.1 We report below the photoisomeriza-
tion of several cis-1,2-diphenylcyclopropane derivatives to the
chiral trans forms in which asymmetric induction has been
enhanced with the use of a confined medium. 1,2-Diph-
enylcyclopropane itself has played a central role in the quest for
new methods of asymmetric induction in organic photo-
chemistry.2 Following the original report by Hammond and
Cole (ee 6.7%),2a asymmetric induction during the isomeriza-
tion of cis-1,2-diphenylcyclopropane to the trans isomer has
been investigated by at least five groups, and the best ee
obtained thus far is only 10%.2b–f Our interest in the parent
system in the context of asymmetric induction faded when cis-
1,2-diphenylcyclopropane failed to isomerize to the trans form
within alkali cation-exchanged Y zeolite.3
We now report that introduction of a third substituent, such as
a carboxamide group onto the cyclopropane ring (e.g., amides
of 2b,3b-diphenylcyclopropane-1a-carboxylic acid, Scheme 1)
solves the problem of lack of reactivity, and the chiral trans
isomers were obtained upon irradiation of the 2b,3b-diph-
enylcyclopropane-1a-carboxamides within alkali cation-ex-
changed Y zeolites. The structure and energy of Li+ ion binding
to the cis isomer of amide 1b calculated at the ab-initio level
(RHF/3-21G, Gaussian 98)4 accounted for the difference in the
photobehavior between the parent cis-1,2-diphenylcyclopro-
pane and its amides 1a–k. The site of Li+ ion binding is different
in these two types of molecules (Fig. 1). While in the parent
molecule, the cation binds to the cis-phenyl groups via a cation–
p interaction,5 in the amide derivative the Li+ ion binds to the
carboxamide group via a dipolar interaction.6 Thus, while a
cation-imposed barrier for cis to trans conversion is likely in the
† Electronic supplementary information (ESI) available: experimental
details of irradiation, extraction and analysis of products, and representative
synthesis and spectral data of reactant cis and product trans isomers; total
number of pages 21. See http://www.rsc.org/suppdata/cc/b2/b200640e/
Scheme 1
Fig. 1 Structures of Li+ complex of cis-1,2-diphenylcyclopropane (A), (2)-1-phenylethylamide of 2b,3b-diphenylcyclopropane-1a-carboxylic acid (B), and
its Li+ complex (C) as calculated by RHF/3-21G. Computed cation interaction energies are also shown.
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CHEM. COMMUN., 2002, 830–831
This journal is © The Royal Society of Chemistry 2002

were obtained in 2% diastereomeric excess (de; except 1f
where the de is 20%). In stark contrast to the solution results,
photolysis of amides 1a–j as adsorbed on zeolites LiY, NaY or
KY afforded the trans isomers with deAs. in the range of 20–83%
(Table 1).
nitrogen lone pair interactions control the conformation of Na+
bound phenylalanine. Results of our computation on 1b is
consistent with this reasoning. A comparison of the structure of
free and Li+-complexed 1b (Fig. 1) suggests that the Li+ ion
causes the chiral auxiliary to move closer to the 2,3-diphenyl
portion of the molecule. A comparison of the structures of
cation-bound and cation-free 1b reveals that in the former the
two phenyl groups will experience different extents of steric
hindrance upon rotation to the trans geometry. We recognize
that the calculated conformation may not be applicable in
zeolites, but as a working hypothesis this appears to be a good
starting point. It appears that presence of either a phenyl or
carboalkoxy or both is required in the chiral auxiliary to obtain
significant asymmetric induction. For example 1k which does
not contain any of these groups gives a very low de.
As presented in Table 1 the cations not only control the extent
of diastereoselectivity but also the isomer that is being
enhanced. Based on density functional calculations and low
energy collisionally activated and thermal radiative dissociation
experiments a difference in binding pattern between Li+ and K+
ions with glycine and valine has been proposed.8 Such a
phenomenon may likely be involved within a zeolite and could
be the cause for the observed cation controlled diastereomer
switching within a zeolite.
The examples provided here demonstrate convincingly that
the influence of a chiral center present as a chiral auxiliary can
be enhanced significantly when the photoreaction is carried out
within a zeolite. Examination of the zeolite interior, in which the
reactant molecule is held, suggests that the most likely factor
responsible for the change in de between solution and zeolite is
the difference in conformational preference for the reactant
molecule in these two media. In solution the influence of cations
are wiped out by solvation of cations by the solvent molecules.
Cations present in zeolites being only partially co-ordinated to
the surface oxygen are free to interact with included guest
molecules. X and Y zeolites contain high concentrations ( ~ 5
M) of exchangable cations making them seemingly open
structures of alkali salts with zeolite framework as the anion.
We believe that cations present in zeolites can be cleverly
exploited to control the chemical behaviour of organic mole-
cules.
The amides 1a–c and 1e gave the highest deAs. (80–83%) of
any of the systems examined thus far in zeolites.7 The results for
these two systems are highlighted below. Irradiation of
1-phenylethylamide 1a–c in hexane–methylene chloride solu-
tion gave the trans isomers in ~ 2% de. As illustrated in Table
1, when 1-phenylethylamide included in LiY was irradiated, the
trans isomer was obtained in 80% de. The fact that the same
chiral auxiliary failed to effect asymmetric induction during
solution irradiation suggests that the confined space of the
zeolite is essential to force a chirally significant interaction
between the amide auxiliary and the site of reaction on the
3-membered ring. Similarly, the amino acid-derived chiral
auxiliary 1e gave excellent results in LiY (de 83%) but not in
solution (de 2%). The following three observations suggest that,
in addition to the confined space, the cations present in a zeolite
play a crucial role in the asymmetric induction process: (a) for
amides 1a–c and 1e, the extent of de as well as the identity of the
isomer being enhanced is dependent on the cation. For example,
in the case of amide 1a the de observed in LiY, NaY and KY are
80%, 28%, 14% respectively. More importantly, while LiY
favoured the formation of isomer B (the second of the two
diastereomeric peaks eluted from GC; SE-30 column), NaY and
KY gave some A in excess. A similar observation was made
with amide 1e: LiY gave 83% of isomer B while KY led to an
80% excess of isomer A. (b) The extent of de within LiY
depends on the water content. For example, in the case of amide
1a, saturating the LiY with water dramatically reduced the de
from 80% (dry) to 8% (wet). We believe that co-ordination of
water to the cation reduces the influence of the cation on the
reaction. (c) Adsorbing the amides on a silica surface, which
does not contain cations, gave low deAs. (8%). Silica surface
differs from zeolites in terms of cavity size as well as silica–
alumina content.
The role of cations in controlling asymmetric induction
within a zeolite is supported by various experimental and
computational results on cation–amino acid complexation
reported in recent years.6,8 We believe that the most likely factor
responsible for the changes in diastereoselectivity observed
upon irradiation of the amide derived from phenylalanine
methyl ester and 2b,3b-diphenylcyclopropane-1a-carboxylic
acid between solution and KY zeolite (de: 2% vs. 53%) is the
conformational preference for the reactant molecule in these
two media. The interaction between the cation present in a
zeolite and the reactant most likely aids a conformation in which
the asymmetric center of the chiral auxiliary is closer to the
reaction site. Recently, as expected, the computed conforma-
tions of free and Na+ bound phenylalanine have been reported to
be different.6b–d Cation–p, dipolar cation–ONC and cation–
VR thanks the National Science Foundation for support of the
research (CHE-9904187). JRS thanks the National Sciences and
Engineering Research council of Canada for financial sup-
port.
Notes and references
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95, 8472; (c) A. Faljoni, K. Zinner and R. G. Weiss, Tetrahedron Lett.,
1974, 13, 1127; (d) A. Ueno, F. Toda and Y. Iwakura, J. Polym. Sci. Poly.
Chem. Ed., 1974, 12, 1841; (e) L. Horner and J. Klaus, Liebigs Ann.
Chem., 1979, 1232; (f) Y. Inoue, N. Yamasaki, H. Shimoyama and A. Tai,
J. Org. Chem., 1993, 58, 1785.
Table 1 Diastereomeric excess obtained upon direct irradiation of amides
1a–k included within MY zeolitesa
Compound
Solution
Li+
Na+
K+
3 P. Lakshminarasimhan, R. B. Sunoj, J. Chandrasekhar and V. Rama-
murthy, J. Am. Chem. Soc., 2000, 122, 4815.
1a
1b
1c
1d
1e
1f
1g
1h
1i
2-B
0
80-B
82-B
77-B
29-B
83-B
39-B
26-B
34-B
10-A
21-A
7-A
25-A
22-A
27-A
24-A
21-A
31-A
22-A
22-A
32-A
40-A
7-A
14-A
13-A
13-A
26-A
80-A
61-A
46-A
31-A
53-A
44-A
3-A
4 Gaussian 98, Revision A.9 Gaussian, Inc., Pittsburgh, PA, USA, 1998.
5 J. C. Ma and D. A. Dougherty, Chem. Rev., 1997, 97, 1303.
6 (a) D. J. Raber, N. K. Raber, J. Chandrasekhar and P. V. R. Schleyer,
Inorg. Chem., 1984, 23, 4076; (b) R. C. Dunbar, J. Phys. Chem. A, 2000,
104, 8067–8074; (c) F. M. Siu, N. L. Ma and C. W. Tsang, J. Am. Chem.
Soc., 2001, 123, 3397–3398.
7 (a) A. Joy, S. Uppili, M. R. Netherton, J. R. Scheffer and V. Ramamurthy,
J. Am. Chem. Soc., 2000, 122, 728; (b) E. Cheung, K. C. W. Chong, S.
Jayaraman, V. Ramamurthy, J. R. Scheffer and J. Trotter, Org. Lett.,
2000, 2, 2801.
8 (a) R. A. Jockusch, A. S. Lemoff and E. R. Williams, J. Am. Chem. Soc.,
2001, 123, 12255–12265; (b) T. Wyttenbach, M. Witt and M. T. Bowers,
J. Am. Chem. Soc., 2000, 122, 3458–3464; (c) R. A. Jockusch, W. D.
Price and E. R. Williams, J. Phys. Chem. A, 1999, 103, 9266–9274; (d)
S. Hoyau and G. Ohanessian, Chem. Eur. J., 1998, 4, 1561–1569.
1-B
2-B
2-A
20-A
3-A
5-B
2-A
1-A
2-B
1j
1k
a Analyses were performed by GC using an SE-30 column. The first
diastereomeric peak eluted from the GC column is arbitrarily assigned as
A.
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