Enhanced enantio- and diastereoselectivity via confinement and cation binding: Yang photocyclization of 2-benzoyladamantane derivatives within zeolites

Article abstract of DOI:10.1021/jo0260793

Irradiation of 2-benzoyladamantane derivatives in zeolites yields the endo-cyclobutanols as the only photoproduct via a γ-hydrogen abstraction process. The cyclobutanols readily undergo retroaldol reaction to give δ-ketoesters. The enantiomeric excess (ee) in the endo-cyclobutanols is measured by monitoring the ee in the ketoesters. Whereas in solution the ee in the product ketoester is zero, within achiral NaY zeolite, in the presence of a chiral inductor such as pseudoephedrine, ee's up to 28% have been obtained. The influence of zeolite on several chiral esters of 2-benzoyladamantane-2-carboxylic acids has also been examined. Whereas in solution the diastereomeric excess is <15%, in zeolite the δ-ketoesters are obtained in 79% de (best examples). Ab initio computations suggest that enhancement of chiral induction within zeolites is likely to be due to cation complexation with the reactant ketone. Alkali ion-organic interaction, a powerful tool, is waiting to be fully exploited in photochemical and thermal reactions. In this context zeolites could be a useful medium as one could view them as a reservoir of "naked" alkali ions that are only partially coordinated to the zeolite walls.

Full text of DOI:10.1021/jo0260793

En h a n ced En a n tio- a n d Dia ster eoselectivity via Con fin em en t a n d
Ca tion Bin d in g: Ya n g P h otocycliza tion of 2-Ben zoyla d a m a n ta n e
Der iva tives w ith in Zeolites†
Arunkumar Natarajan,‡ Abraham J oy,‡ Lakshmi S. Kaanumalle,‡ J ohn R. Scheffer,§ and
V. Ramamurthy*,‡
Department of Chemistry, Tulane University, New Orleans, Louisiana 70118, and Department of
Chemistry, University of British Columbia, Vancouver, BC, Canada V6T 1Z1
murthy@tulane.edu
Received J une 19, 2002
Irradiation of 2-benzoyladamantane derivatives in zeolites yields the endo-cyclobutanols as the
only photoproduct via a γ-hydrogen abstraction process. The cyclobutanols readily undergo retro-
aldol reaction to give δ-ketoesters. The enantiomeric excess (ee) in the endo-cyclobutanols is
measured by monitoring the ee in the ketoesters. Whereas in solution the ee in the product ketoester
is zero, within achiral NaY zeolite, in the presence of a chiral inductor such as pseudoephedrine,
ee’s up to 28% have been obtained. The influence of zeolite on several chiral esters of 2-benzoy-
ladamantane-2-carboxylic acids has also been examined. Whereas in solution the diastereomeric
excess is <15%, in zeolite the δ-ketoesters are obtained in 79% de (best examples). Ab initio
computations suggest that enhancement of chiral induction within zeolites is likely to be due to
cation complexation with the reactant ketone. Alkali ion-organic interaction, a powerful tool, is
waiting to be fully exploited in photochemical and thermal reactions. In this context zeolites could
be a useful medium as one could view them as a reservoir of “naked” alkali ions that are only
partially coordinated to the zeolite walls.
In tr od u ction
“zeolite confinement strategy” is effective even when the
chiral auxiliary fails to act in an isotropic solution
medium.
During the past several years we have shown that
zeolites can serve as useful media to bring about modest
enantio- and diastereoselectivity during photochemical
reactions.1 A major deficiency of utilizing zeolites as
reaction media for asymmetric induction is that zeolites
are not chiral,2 and this serious limitation has to be
overcome. Our approach in this context has been to
chirally modify the zeolite.3 Another successful approach
we have introduced is to use achiral zeolites to force an
interaction between a chiral auxiliary and a reactant
center in the same molecule.4 We have shown that this
Although they do not yet allow us to formulate basic
rules regarding chiral induction within zeolites, such
studies have established the potential of the zeolite-based
chiral strategy.5 Our long range objective is to develop
the zeolite-based chiral strategy as a general method to
conduct enantio- and diastereoselective photoreactions.
This goal can be reached only when we fully understand
how zeolites are able to force intimate interactions
between a chiral moiety and the reaction center. In this
context we have examined the photochemical behavior
of 2-benzoyladamantanes 1a and 1b and 2-benzoylada-
mantane-2-carboxylic acid derivatives 5a -d within fau-
jasite zeolites (MY where M is an alkali ion).6 Upon
excitation,
* To whom correspondence should be addressed. Ph: 504 862 8135.
Fax: 504 865 5596.
† Dedicated to Professor W. Adam on the occasion of his 65th
birthday.
‡ Tulane University.
§ University of British Columbia.
(3) (a) J oy, A.; Robbins, R. J .; Pitchumani, K.; Ramamurthy, V.
Tetrahedron Lett. 1997, 8825. (b) J oy, A.; Scheffer, J . R.; Corbin, D.
R.; Ramamurthy, V. J . Chem. Soc., Chem. Commun. 1998, 1379. (c)
J oy, A.; Corbin, D. R.; Ramamurthy, V. In Proceedings of 12th
International Zeolite Conference; Traecy, M. M. J ., Marcus, B. K.,
Bisher, B. E., Higgins, J . B., Eds.; Materials Research Society:
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V. Org. Lett. 2000, 2, 119.
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Org Lett. 2002, 4, 1443. (b) Sivaguru, J .; Scheffer, J . R.; Ramamurthy,
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murthy, V. Org Lett. 2002, 4, 87. (d) Chong, K. C. W.; Sivaguru, J .;
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Mater. 1997, 9, 2168. (b) Szostak, R.; Handbook of Molecular Sieves;
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10.1021/jo0260793 CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/08/2002
J . Org. Chem. 2002, 67, 8339-8350
8339

Natarajan et al.
SCHEME 1
SCHEME 2
SCHEME 3
these molecules yield cyclobutanols via γ-hydrogen ab-
straction (Schemes 1 and 2).7 Cyclobutanols derived from
compounds 5a -d readily undergo retro-aldol reaction to
yield δ-ketoesters 8 and 9 in which the chiral information
is stored.6c,8
Previously we reported the asymmetric Yang photo-
cyclization reactions of ketones 10 and 12 (Scheme 3).9
Of the two, ketone 10 gives only one cyclobutanol
diastereomer, both in solution and in zeolites, while
ketone 12 gives two cyclobutanol diastereomers, 13 and
(5) The use of zeolites to enhance chiral induction in thermal
reactions is also being explored by several groups: (a) Thomas, J . M.;
Maschmeyer, T.; J ohnson, B. F. G.; Shephard, D. S. J . Mol. Catal. A.
Chem. 1999, 141, 139. (b) Thomas, J . M.; Raja, R. J . Chem. Soc., Chem.
Commun. 2001, 675. (c) Hutchings, G. J . J . Chem. Soc., Chem.
Commun. 1999, 301. (d) Clark, J . H.; Macquarrie, D. J . J . Chem. Soc.,
Chem. Commun. 1998, 853. (e) J ohnson, B. F. G.; Raynor, S. A.;
Shephard, D. S.; Mashmeyer, T.; Thomas, J . M.; Sankar, G.; Bromley,
S.; Oldroyd, R.; Gladden, L.; Mantle, M. D. J . Chem. Soc., Chem.
Commun. 1999, 1167. (f) Raynor, S. A.; Thomas, J . M.; Raja, R.;
J ohnson, B. F. G.; Bell, R. G.; Mantle, M. D. J . Chem. Soc., Chem.
Commun. 2000, 1925. (g) De Vos, D. E.; Meinershagen, J . L.; Bein, T.
Angew. Chem., Int. Ed. Engl. 1996, 35, 2211. (h) Ogunwumi, S. B.;
Bein, T. J . Chem. Soc., Chem. Commun. 1997, 901. (i) Corma, A.;
Iglesias, M.; del Pino, C.; Sanchez, F. J . Chem. Soc., Chem. Commun.
1991, 1253. (j) Zhou, X. E.; Yu, X. Q.; Huang, J . S.; Che, C. M.; Li, S.
G.; Li, L. S. J . Chem. Soc., Chem. Commun. 1999, 1789. (k) Paola, P.;
Langham, C.; McMorn, P.; Bethell, D.; Bulman-Page, P. C.; Hancock,
F. E.; Sly, C.; Hutchings, G. J . J . Chem. Soc., Perkin Trans. 2 2000,
143. (l) Paola, P.; McMorn, P.; Murphy, D.; Bethell, D.; Page, P. C. B.;
Hancock, F. E.; Sly, C.; Kerton, O. J .; Hutchings, G. J . J . Chem. Soc.,
Perkin Trans. 2 2000, 2008. (m) Kim, G. J .; Park, D. W. Catal. Today
2000, 63, 537.
(6) Photochemistry of some of these compounds in the crystalline
state has been reported: (a) Leibovitch, M.; Olovsson, G.; Scheffer, J .
R.; Trotter, J . J . Am. Chem. Soc. 1997, 119, 1462. (b) Leibovitch, M.;
Olovsson, G.; Scheffer, J . R.; Trotter, J . J . Am. Chem. Soc. 1998, 120,
12755. (c) Cheung, E.; Netherton, M. R.; Scheffer, J . R.; Trotter, J .;
Zenova, A. Tetrahedron Lett. 2000, 41, 9673.
(7) (a) Wagner, P. J .; Park, B. S. Org. Photochem. 1991, 11, 227. (b)
Yang, N. C.; Yang, D. H. J . Am. Chem. Soc. 1958, 80, 2913. (c) Wagner,
P. J . Acc. Chem. Res. 1989, 22, 83. (d) Scaiano, J . C. Acc. Chem. Res.
1982, 15, 252.
(8) (a) Hasegawa, T.; Arata, Y.; Endoh, M.; Yoshioka, M. Tetrahe-
dron 1985, 41, 1667. (b) Hasegawa, T.; Nishimura, M.; Kodama, Y.;
Yoshioka, M. Bull. Chem. Soc. J pn. 1990, 63, 935.
8340 J . Org. Chem., Vol. 67, No. 24, 2002

Yang Photocyclization within Zeolites
TABLE 1. En a n tiom er ic Excess Obta in ed in th e
Ir r a d ia tion of 1a a n d 1b in Na Y in P r esen ce of Va r iou s
Ch ir a l In d u ctor sa
14. The zeolites used to study these reactions were X and
Y. While irradiation of compound 10 in NaY with (-)-
ephedrine showed enantioselectivity in favor of the (+)-
isomer of compound 11, the same chiral inductor favored
the (-)-isomer of compound 11 in NaX, although to a
much smaller extent. A similar reversal was also seen
when (+)-ephedrine was used as the chiral inductor. The
ratio of the two cyclobutanols from ketone 12 depends
on the medium in which the irradiation is conducted. In
hexane, the ratio of trans- to cis-cyclobutanol is 2.8,
whereas in NaY the ratio is 1.0. The results highlighted
in Scheme 3 show that whereas cis-cyclobutanol 13 was
formed in moderate enantioselectivity, the trans isomer
14 was formed with very low enantioselectivity. One
disappointing result from these studies was that the
enantiomeric excess of the cyclobutanols from ketones 10
and 12 could not be improved beyond 35%. In our
continued search for a better system, we have examined
the photobehavior of achiral 2-benzoyladamantanes 1a
and 1b within chirally modified Y zeolites. To explore
the versatility of the “chiral auxiliary approach” further,
the photochemistry of the chiral 2-benzoyladamantane-
2-carboxylic acid derivatives 5a -d has been examined
within achiral MY zeolites (M ) alkali ion).
% ee
chiral inductor
ketone 1a
ketone 1b
(-)-pseudoephedrine
(+)-pseudoephedrine
(+)-AMPPb
(+)-methyl benzyl amine
(-)-norephedrine
(+)-norephedrine
L-phenylalaninol
(+)-diethyl tartrate
L-valinol
32 (B)
28 (A)
32 (A)
22 (A)
15 (B)
12 (A)
14 (B)
11 (B)
7 (B)
30 (B)
25 (A)
-
3 (A)
2 (A)
-
5 (B)
-
-
0
(-)-ephedrine
2 (A)
a
The ee was determined on HPLC column OD (99% hexane-
iPrOH; 0.5 mL/min; 235 nm. All irradiations were carried out in
NaY at 22 °C. The first peak to elute from the column is assigned
b
as peak A and the second as B. (+)-AMPP: (+)-2-amino-3-
methoxy-1-phenyl-1-propanol.
product within zeolites and reextracting them from the
zeolite. The ee/de of the product included and extracted
were identical, indicating that the zeolite is not selec-
tively retaining any one isomer. By employing a calibra-
tion compound we made sure that the 95% of the included
products could be re-extracted from the zeolite.
Resu lts
The enantioselectivities induced in the cyclobutanol
photoproduct from ketones 1a and 1b in NaY are listed
in Table 1. In both cases in solution, even in the presence
of chiral inductors, the cyclobutanol was formed only as
a racemic mixture. However, within NaY zeolite in the
presence of certain chiral inductors, an enantiomeric
excess was induced in the product cyclobutanol, although
only to a modest amount. Using (-)-pseudoephedrine as
the chiral inductor, the product cyclobutanol from 1a was
obtained in 32% ee, while in the presence of (+)-
pseudoephedrine, as expected, the opposite enantiomer
was obtained in 28% ee. Irradiation with NaY/(+)-2-
amino-3-methoxy-1-phenyl-1-propanol gave the product
in 32% ee, while irradiation in NaY/(+)-methylbenzyl-
amine gave the product in 22% ee. Several other chiral
inductors listed in Table 1 gave poor ee’s. In the case of
ketone 1b only pseudoephedrine gave the product in 30%
ee; all other chiral inductors examined gave almost
racemic cyclobutanol (Table 1). We are encouraged by the
fact that, unlike solution, NaY is able to bring about some
degree of chiral induction. At the same time we are
discouraged by the observation that the extent of chiral
induction is, at best, modest.
The adamantyl ketoesters derived from a (-)-menthol,
(+)-isomenthol, (+)-isopinocampheol, and (-)-2-methyl-
1-butanol were synthesized from adamantane-2- carboxyl-
ic acid (see Experimental Section), and their asymmetric
photochemistry within MY (M ) alkali ion) zeolite was
investigated. A typical procedure consisted of adding
activated NaY (300 mg) to a hexane solution of ketone 5
(5 mg). The solution was stirred for 12 h at 60 °C after
which the zeolite complexed with ketone 5 was filtered
and dried under vacuum (3 × 10-3 Torr) at 65 °C for 6 h
prior to irradiation. Analysis of the filtrate (hexane) by
GC indicated that only 60% of the adamantyl ketone was
included within the zeolite. This could be indicative that
ketone 5 is too large to fit completely within the zeolite.
The same result was obtained when the loading proce-
The influence of chiral environment during the Yang
photocyclization of the adamantyl ketones 1a , 1b, and
5a -d was examined within faujasite zeolites. In the first
two cases the chiral moiety that influences the reaction
is an independent molecule (chiral inductor), and in the
latter set of molecules it forms a part of the reactant
molecule although remotely placed from the reaction
center (chiral auxiliary). A typical procedure of loading
the achiral ketones 1a and 1b within the zeolite consisted
of adding activated NaY (300 mg) to a stirred hexane
solution of the chiral inductor (0.1 mmol, S ) 1.0). The
complexed zeolite was filtered, washed, and dried. This
was added to a stirred solution of the adamantyl aryl
ketone (0.01 mmol) in hexane. The loading level of the
ketone was kept at one molecule for every 10 supercages
( S ) 0.1). A higher ratio of the chiral inductor was
employed to maximize the chances of every ketone
molecule being adjacent to a chiral inductor within the
supercage. The resulting doubly loaded zeolite complex
was then filtered and washed with hexane. Analysis of
the filtrate (hexane solution) by GC indicated that the
adamantyl ketone was completely incorporated within
the NaY. The zeolite complex was irradiated as a hexane
slurry, the product(s) were extracted from the zeolite with
diethyl ether, and the enantiomeric excess of the product
determined using chiral HPLC (Chiralcel OD column).
The products were identified by comparison with those
obtained during crystalline irradiations and character-
ized previously.6 The only products obtained upon ir-
radiation of the above ketones in zeolites are the cyclo-
butanols resulting from γ-hydrogen abstraction. The
dependability of the measured ee/de was checked by
including a racemic or 1:1 diasteromeric mixture of the
(9) (a) Leibovitch, M.; Olovsson, G.; Sundarababu, G.; Ramamurthy,
V.; Scheffer, J . R.; Trotter, J . J . Am. Chem. Soc. 1996, 118, 1219. (b)
Sundarababu, G.; Leibovitch, M.; Corbin, D. R.; Scheffer, J . R.;
Ramamurthy, V. J . Chem. Soc., Chem. Commun. 1996, 2159.
J . Org. Chem, Vol. 67, No. 24, 2002 8341

Natarajan et al.
SCHEME 4
SCHEME 5
dure was repeated several times. The ketone remaining
in hexane solution was removed, ketone 5 included within
zeolite was irradiated (450-W medium-pressure lamp,
Pyrex filter) as a hexane slurry for 60 min, and the
product was extracted with THF. The conversion of the
starting material to product was kept <50% in these
irradiations. The isolated photoproducts in these reac-
tions are the δ-ketoesters 8 and 9, which are formed by
the retro-aldol ring opening of the corresponding cyclobu-
tanols 6 and 7 (Scheme 4). This reaction has literature
precedent and the formation of δ-ketoesters was expect-
ed.6c,8 The diastereoselectivity of the cyclobutanol inter-
mediates is transformed as de in the δ-ketoesters, which
were analyzed by HPLC.
Irradiation of 2-benzoyladamantane-2-carboxylic acid
ester derivatives 5a -d in acetonitrile and hexane gave
the δ-ketoesters 8a -d and 9a -d in 4-22% de. Clearly,
even in isotropic solution the chiral auxiliary has an
influence on the asymmetric photochemistry of the parent
ketone. To our delight, when these ketones were irradi-
ated within MY zeolites (M ) Li+, Na+, and K+), the de
obtained was substantially higher (the maximum being
79%) than in acetonitrile or hexane. The de obtained in
solution and in various zeolites is summarized in Scheme
5, and typical GC or HPLC traces of the photoproducts
in one zeolite and acetonitrile solution are shown in
Figure 1. The figure nicely illustrates the remarkable
influence of zeolites in enhancing de.
Discu ssion
As in isotropic solution, the 2-benzoyladamantane
derivatives preferentially yield the endo-cyclobutanols
when irradiated in zeolites.6 Neither exo-cyclobutanol nor
the fragmentation products are formed. Preferential
formation of the endo product can be understood on the
basis of the structural constraints on the system. This
aspect of the reaction has been discussed previously in a
publication by one of the current authors.6 However, a
brief discussion is appropriate.
When initially formed, the 1,4-diradical generated via
γ-hydrogen abstraction would have its two p-orbitals
perpendicular to each other in a folded conformation
(Scheme 6).7 By rotating about its central and terminal
8342 J . Org. Chem., Vol. 67, No. 24, 2002

Yang Photocyclization within Zeolites
undergo three reactions: cyclization, fragmentation, and
reverse hydrogen transfer. The geometric requirements
for each of these reactions are slightly different. The
fragmentation process can only occur when the two
p-orbitals of the 1,4-diradical are parallel to the central
CsC σ-bond that is being broken. Both cyclization and
reverse hydrogen transfer require that the two ends of
the diradical be close to one another, i.e., it requires a
cisoid conformation. Because of these constraints, the
transoid conformation can only fragment, whereas the
cisoid conformation can do all three, cyclization, frag-
mentation, and reverse hydrogen transfer (Scheme 6).
In the case of the 2-benzoyladamantyl system, because
of geometric constraints the 1,4-diradical 15 generated
via γ-hydrogen abstraction cannot reach the transoid
geometry and also the two p-orbitals at the termini of
the 1,4-diradical cannot become fully parallel to the
central CsC bond (Scheme 7). However partial alignment
of the orbital on C1 with the C2-C3 bond can initiate
cleavage. This geometry can be reached only if the
molecule can overcome an eclipsed interaction between
the aryl and the R group at C2 (diradical 16 in Scheme
7). In general cleavage is not favored in systems contain-
ing methyl substitution at C2. To understand why endo-
cyclobutanols are formed in preference to the exo isomers
both in solution and in zeolites, one should closely
examine the factors involved in the transformation of the
initially formed 1,4-diradical 15 to the other conformer
17 (Scheme 7). In the minimum energy conformation
computed (RB3LYP/6-31G(d)) for 2-methyl-2-benzoyl ad-
amantane the carbonyl group is not at the center but
tilted toward one of the two prochiral hydrogens (Figure
2; note the distance between the two prochiral hydrogens
marked 1 and 2).10 Excitation of the ketone present in
this conformation would generate a 1,4-diradical, which
cannot fragment. On the other hand, a slight tilting and
rotation around the C1sC2 bond places the orbitals in
an arrangement suitable for cyclization. The rotation that
is needed to yield the endo-cyclobutanol would be ex-
pected to occur smoothly, as it involves no steric hin-
drance between the phenyl group and the substituent
methyl group at the C2 carbon. On the other hand, the
rotation that is needed to reach the diradical 17 precursor
for the exo-cyclobutanol from the diradical 15 via the
diradical 16 involves a steric interaction between the aryl
group and the substituent at the C2 carbon (eclipsing
interaction). Since the conformations of 15, 16, and 17
(initially formed, precursor for endo adduct, and precur-
sor for exo adduct) are ideally suited for intersystem
crossing from the triplet to the singlet state, the easily
formed 1,4-diradical would undergo ISC and close to give
F IGURE 1. A comparison of the diastereomeric excess (de)
in solution and in zeolite. GC and HPLC traces corresponding
to the diastereomeric products upon irradiation of chiral esters
of 2-benzoyladamatane-2-carboxylic acid. Peaks A and B
correspond to the first and second diastereomers as they elute.
The configurations of A and B are not known.
SCHEME 6
(10) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J . R.; Zakrzewski, V. G.; Montgomery, J . A.,
J r.; Stratmann, R. E.; Burant, J . C.; Dapprich, S.; Millam, J . M.;
Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J .;
Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo,
C.; Clifford, S.; Ochterski, J .; Petersson, G. A.; Ayala, P. Y.; Cui, Q.;
Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.;
Foresman, J . B.; Cioslowski, J .; Ortiz, J . V.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.;
Fox, D. J .; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; J ohnson, B. G.; Chen,
W.; Wong, M. W.; Andres, J . L.; Head-Gordon, M.; Replogle, E. S.;
Pople, J . A. Gaussian 98, revision A.9; Gaussian, Inc.: Pittsburgh, PA,
1998.
CsC bonds the 1,4-diradical can adopt cisoid and tran-
soid (anti) conformations (Scheme 6). The 1,4-diradical
that exists in these conformations can in principle
J . Org. Chem, Vol. 67, No. 24, 2002 8343

Natarajan et al.
F IGURE 2. Conformation of (a) 2-methyl-2-benzoyl adamantane and its complex with Li+ as computed at RB3LYP/6-31G(d)
level. Note that the benzoyl carbonyl is tilted toward one of the two prochiral hydrogens. The distance between the carbonyl
oxygen and the prochiral hydrogens are included. The binding energy computed at RHF/3-21G* level are given in paranthesis.
SCHEME 7
the cyclobutanol. In this case it would be the formation
of the diradical 15 and the endo-cyclobutanol.
racemic mixture, and this is what happens in the absence
of a chiral influence both in solution and in zeolites.
However, the presence of a chiral inductor changes the
scenario. In Scheme 8, the discrimination of the diaste-
reotopic hydrogens by the carbonyl group is illustrated
in a schematic fashion. When a chiral inductor interacts
weakly with the carbonyl group, the previously enan-
tiotopic hydrogens become diastereotopic and therefore
nonequivalent toward abstraction. In Scheme 8 the
interacting group is marked “s” and the two diaste-
reotopic hydrogens are marked “a” and “b”. As illustrated
in the Scheme, in the presence of a chiral inductor the
steric environments around the two hydrogens are not
the same. The C-H “a” is closer to a bulky group (marked
“l”), whereas the C-H “b” is next to a less bulky group
(marked “m”) of the chiral inductor. This difference in
environment is likely to result in preferential abstraction
of one of the two hydrogens, leading to enantiomeric
The final part of the discussion relates to the chiral
induction during cyclobutanol formation. In the 2-ben-
zoyladamantyl system there are two prochiral hydrogens
(at C4 and C6). As mentioned above, the computed
minimum energy conformation (RB3LYP/6-31G(d)) for
2-methyl-2-benzoyl adamantane indicates that the car-
bonyl group is tilted toward one of the two prochiral
hydrogens (Figure 2). Within zeolite the cation is ex-
pected to interact with the reactant ketone 1. The
computed structure (RB3LYP/6-31G(d)) for the Li+-2-
methyl-2-benzoyl adamantane complex shown in Figure
2 also indicates that the carbonyl group is tilted toward
one side. Based on symmetry the two structures in which
the carbonyl group is tilted toward either C4 or C6 are
of equal energy. The presence of equal amounts of the
two structures would yield the endo-cyclobutanol as a
8344 J . Org. Chem., Vol. 67, No. 24, 2002

Yang Photocyclization within Zeolites
SCHEME 8
excess in the product cyclobutanol.The fact that in
solution, even in the presence of a chiral inductor such
as pseudoephedrine, no chiral induction is obtained
suggests that the interaction between the chiral inductor
and the reactant is too weak to persist and that reactions
occur from uncomplexed ketone molecules. We believe
that the ability of zeolites to preserve this weak interac-
tion is the basis of the observed modest chiral induction
in this medium. Although we do not fully understand how
zeolites are able to preserve the weak interaction between
the reactant and chiral inductor molecules, we believe
that the cations present in the zeolite play an important
role. As seen in Table 1, the chiral inductor pseudoephe-
drine is able to bring about a 30% ee in the cyclobutanols
derived from ketones 1a and 1b within NaY. This is
significant, as the same chiral inductor is ineffective in
acetonitrile solution.
In general, the chiral auxiliary method has given better
results within zeolites than the chiral inductor approach,
and the present study is no exception (Scheme 5 and
Figure 1).4 The chiral auxiliaries we have examined in
this study do not contain any special chromophores. As
in achiral ketone 1, the systems with a chiral auxiliary
attached to the C2 carbon should have two conformations
in which the carbonyl chromophore is tilted toward one
or the other diastereotopic hydrogens at C4 and C6. The
two lowest energy conformations computed (RB3LYP/6-
31G(d)) for the menthyl ester of 2-benzoyladamatane-2-
carboxylic acid are shown in Figure 3. Clearly the
carbonyl is tilted toward either side and the two conform-
ers do not have the same energy. As indicated in Figure
3, the energy difference between the two structures is
2.3 kcal/mol. As a result of the flexible nature of the chiral
auxiliary the energy difference between the two conform-
ers must be smaller than the computed energy for the
frozen conformations. This most likely results in a low
de in solution.
ketones are introduced within a zeolite, the cations
interact with the chromophores and thus influence the
conformation of the molecule. The structures of the Li+
complex of the menthyl ester of 2-benzoyladamatane-2-
carboxylic acid was computed at the RB3LYP/6-31G(d)
level (Figures 4 and 5). Three structures in which the
cation is bound to three different sites are identified. In
structure “a” in Figure 4 the cation cooperatively inter-
acts with the carbonyl oxygen of the ester and the phenyl
group (interaction energy, -66.20 kcal/mol), and in
structure “b” the interaction is primarily with the phenyl
group (-47.00 kcal/mol). In structure “a” in Figure 5 the
interactions are with both keto oxygen and ester oxygen
(-69.90 kcal/mol). Of the structures shown in Figures 4
and 5 the ones in which the cation is interacting with
both keto oxygen and ester oxygen is the most stable
(Figure 5). As seen in other cases, in this structure also
the keto oxygen is tilted toward one of the two prochiral
hydrogens. Once again, two conformers in which the
carbonyl is tilted toward either side do not have the same
energy. Closer examination indicates that the nature of
interaction between Li+ and menthyl ester of 2-benzoyl-
adamatane-2-carboxylic acid is different in the two
conformers. In structure “a” the interaction is between
the cation and the oxygens of the keto and ester group
(CO-O-C), and in structure “b” the interaction is between
cation and the oxygens of the two carbonyls of the keto
and ester groups. The latter is more stable by 10.42 kcal/
mol (compare with 2.3 kcal/mol in the absence of cation).
In these structures the cation acts as “glue” to restrict
the relative motions of the reactive and chiral auxiliary
portions of the molecule (Figure 5). By this process the
chiral auxiliary is able to exert a stronger influence on
the γ-hydrogen abstraction reaction. Once interconver-
sion between the two conformers is restricted the reaction
will take place from the most stable of the two. Thus
while the chiral auxiliary is essential to differentiate the
two diastereotopic hydrogens, the cation is important to
restrict rotations and freeze the molecule in a conforma-
tion that leads primarily to one cyclobutanol diastere-
omer.
Within zeolites the influence of the chiral auxiliary is
significantly enhanced. Computational results once again
provide a clue to what is likely to be responsible for the
observed enhancement of de within zeolites. When the
J . Org. Chem, Vol. 67, No. 24, 2002 8345

Natarajan et al.
F IGURE 3. The two conformations of menthyl ester of 2-benzoyladamantane-2-carboxylic acid as computed at RB3LYP/6-31G-
(d) level. Note the two conformations in which the carbonyl group is tilted toward the two prochiral hydrogens have different
energies. The distance between the carbonyl oxygen and the prochiral hydrogens are included. The difference in energy computed
at RHF/3-21G* level is given in parentheses.
F IGURE 4. Interaction energies and structures of Li+ complex with menthyl ester of 2-benzoyladamantane-2-carboxylic acid
computed at RB3LYP/6-31G(d) level. Note that the cation location is different in the two structures and the two have different
interaction energies. The interaction energies computed at RHF/3-21G* level are given in parentheses.
The dependence of the de on the cation (Scheme 5) in
all four cases indicates that cation binding to the reactant
molecule plays an important role in the chiral induction
process within zeolites. Consistent with this conclusion
is the finding that inclusion of water into NaY along with
the ketone 5 decreases the de to <10%. In the presence
of water the cation would preferentially bind to water
molecules and thus would have no influence on the
diastereoselectivity. On the basis of the admittedly
limited number of examples discussed above we tenta-
tively conclude that the size and rigidity of the chiral
auxiliary is important. For example, among the com-
pounds 5a -d , the smaller and more flexible 2-methyl-
butyl chiral auxiliary (compound 5c) gives the lowest de.
We recognize that a comprehensive model for chiral
induction within zeolites is still far from complete, and
only small pieces such as those presented here help build
a bigger picture.
The above results suggest that divalent cations such
as Mg2+, Ca2+, and others would provide a much better
selectivity within zeolites. Unfortunately, the use of such
divalent and trivalent cation exchanged zeolites generate
Brønsted acid sites upon activation.11 The use of zeolites
containing Brønsted acid sites are not useful as media
(11) Kao, H. M.; Grey, C. P.; Pitchumani, K.; Lakshminarasimhan,
P. H.; Ramamurthy, V. J . Phys. Chem. 1998, 102, 5627.
8346 J . Org. Chem., Vol. 67, No. 24, 2002

Yang Photocyclization within Zeolites
F IGURE 5. The most stable structure computed (RB3LYP/6-31G(d)) for Li+ complex with menthyl ester of 2-benzoyladamantane-
2-carboxylic acid. In the two structures the sites of interaction of Li+ are different. The carbonyl is tilted toward different prochiral
hydrogens in the two structures. Note the interaction energies are considerably different for the two structures. The interaction
energies computed at RHF/3-21G* level are given in parentheses.
for photochemical reactions because thermal dark reac-
tions predominate.12
assemblies16 have, on the other hand, provided the most
encouraging results. Consistently high (>90%) ee’s have
been obtained in a number of photoreactions. Even
though crystalline and host-guest assemblies have been
very useful in conducting enantioselective photoreactions,
their general applicability thus far has been limited. They
are restricted to systems that form crystalline materials.
We believe that the zeolite approach presented here can
serve as a complimentary method to the solid-state
approach. In principle, zeolites could serve as chiral
media to reactants present in any state (gas, liquid, or
solid). We are, however, still far from realizing the
desired goal of quantitative ee or de in a photochemical
reaction.
Con clu sion
The examples presented above demonstrate convinc-
ingly that the confined space of a zeolite can serve as a
useful medium to achieve asymmetric induction during
a photoreaction. Consistently higher ee’s or de’s have
been obtained within zeolites than those in solution. Of
the two approaches presented, the chiral auxiliary method
gives better results. The confined space and the cations
present within zeolites are believed to be responsible for
the asymmetric induction. Although a model that can
predict the outcome of asymmetric induction with zeolites
as reaction media is currently lacking, experiments in
this direction are underway.
Exp er im en ta l Section
Ma t er ia ls. NaY zeolite was obtained from a commercial
source. Monovalent cation exchanged zeolites (LiY, KY, RbY,
and CsY) were prepared by stirring 10 g of NaY with 100 mL
of a 10% solution of the corresponding metal nitrate in water
for 12 h with continuous refluxing. The zeolite was filtered
and washed thoroughly with distilled water. This procedure
was repeated three times. Subsequently, the zeolite was dried
at 120 °C for about 3 h to obtain the cation exchanged zeolite.
Syn th esis of Ad a m a n tyl P h en yl Keton es. (a ) Syn th esis
of 2-Ben zoyl-2-m eth yla d a m a n ta n e (1a ). The procedure
adopted in this study is slightly different from the one
published previously.6b The overall scheme used to synthesize
the reactants is outlined in Scheme 9. The method of Alberts
et al.17 was used to prepare the adamantane 2-carboxaldehyde.
A dry three-necked 250-mL round-bottomed flask was charged
with methoxymethyltriphenylphosphinechloride, CH3OCH2P-
In the past, chiral solvents, chiral auxiliaries, circularly
polarized light, and chiral sensitizers have been utilized
to conduct enantioselective photoreactions.13 The highest
chiral induction achieved by any of these approaches at
ambient temperature and pressure is ∼30% (2-10% ee
is common in photochemical reactions under the above
conditions). The crystalline state14,15 and solid host-guest
(12) Ramamurthy, V.; Lakshminarasimhan, P. H.; Grey, C. P.;
J ohnston, L. J . J . Chem. Soc., Chem. Commun. 1998, 2411.
(13) (a) Inoue, Y. Chem. Rev. 1992, 92, 741. (b) Rau, H. Chem. Rev.
1983, 83, 535. (c) Pete, J . P. Adv. Photochem. 1996, 21, 135. (d) Everitt,
S. R. L.; Inoue, Y. In Molecular and Supramolecular Photochemistry;
Ramamurthy, V., Schanze, K. S., Eds.; Marcell Dekker: New York,
1999; Vol. 3, p 71. (e) Buschmann, H.; Scharf, H. D.; Hoffmann, N.;
Esser, P. Angew. Chem., Int. Ed. Engl. 1991, 30, 477.
(14) (a) Scheffer, J . R. Can. J . Chem. 2001, 79, 349. (b) Gamlin, J .
N.; J ones, R.; Leibovitch, M.; Patrick, B.; Scheffer, J . R.; Trotter, J .
Acc. Chem. Res. 1996, 29, 203. (c) Leibovitch, M.; Olovsson, G.; Scheffer,
J . R.; Trotter, J . Pure Appl Chem. 1997, 69, 815.
(15) (a) Green, B. S.; Lahav, M.; Rabinovich, D. Acc. Chem. Res.
1979, 12, 191. (b) Addadi, L.; Lahav, M. Pure Appl. Chem. 1979, 51,
1269. (c) Sakamoto, M. Chem. Eur. J ., 1997, 3, 684.
(16) (a) Toda, F. Acc. Chem. Res. 1995, 28, 480. (b) Toda, F.; Tanaka,
K.; Miyamoto, H. In Molecular and Supramolecular Photochemistry;
Ramamurthy, V., Schanze, K., Eds.; Marcell Dekker: New York, 2001;
Vol. 8, p 385.
(17) Alberts, A. H. Wynberg, H.; Strating, J . Synth. Commun. 1972,
2, 79.
J . Org. Chem, Vol. 67, No. 24, 2002 8347

Natarajan et al.
δ 27.8, 28.0, 28.2, 28.9, 31.8, 32.2, 38.2, 38.9, 39.1, 51.6, 126.8,
127.7, 128.4, 144.1.
SCHEME 9
The alcohol obtained above was oxidized with PCC to the
corresponding ketone.18 Pyridinium chlorochromate (325 mg,
1.5 mmol) and sodium acetate (35 mg, 0.4 mmol) were
suspended in dichloromethane (2 mL). The alcohol 127a (242
mg, 1 mmol) dissolved in 1 mL of CH2Cl2 was added in one
portion to the magnetically stirred solution of PCC. The
solution became briefly homogeneous before depositing the
black insoluble reduced reagent. After 2 h, dry ether (10 mL)
was added, and the supernatant was decanted from the black
gum. The insoluble residue was washed with dry ether (3 × 3
mL), and the combined organic solution was passed through
a short pad of Florisil. The solvent was removed to yield the
ketone (230 mg, 95% yield). The ketone 22a was purified by
column chromatography (10% ethyl acetate-hexane): 1H
NMR (CDCl3, 400 MHz) δ 7.90-7.80 (2H, m), 7.60-7.40 (3H,
m), 3.50-3.40 (1H, m), 2.30 (2H, m), 2.10-1.40 (12 H, m); 13
C
NMR (CDCl3, 100 MHz) δ 27.5, 27.9, 30.3, 32.7, 37.4, 38.8,
52.1, 128.0, 128.4, 132.1, 137.3, 204.0; LRMS (EI) m/e (relative
intensity) 241 (3.5), 240 (M+, 20.1), 239 (10.4), 222 (0.9), 197
(1.9), 179 (2.7), 135 (8.0), 120 (2.1), 105 (16.5), 93 (3.5), 79 (3.8),
77 (7.7), 67 (3.6), 41 (2.3); IR cm-1 (KBr pellet) 2950, 1676,
1447, 1364, 1221, 973, 766, 698; UV (methanol) 238 (17,800),
278 (sh. 1500), 339 (80) nm.
The ketone obtained above was methylated following the
published procedure6b to give 1a : 1H NMR (CDCl3, 400 MHz)
δ 7.78-7.64 (2H, m), 7.50-7.30 (3H, m), 2.38 (2H, m), 2.18-
2.07 (2H, m), 1.90-1.62 (10 H, m), 1.60 (3H, s); 13C NMR
(CDCl3, 100 MHz) δ 23.8, 27.0, 27.2, 32.5, 34.1, 35.0, 38.1, 53.1,
127.8, 127.9, 130.7, 139.2, 210.8; LRMS (EI) m/e (relative
intensity) 254 (M+, 3.6), 150 (12.1), 149 (50.0), 148 (9.5), 121
(4.0), 107 (9.4), 105 (9.0), 93 (16.1), 91 (5.5), 81 (11.3), 79 (8.8),
77 (11.6), 67 (8.9), 55 (3.2), 41 (4.2), 32 (4.6); IR cm-1 (KBr
pellet) 2950, 2913, 2862, 1666, 1596, 1462, 1256, 1214, 1163,
1138, 1104, 1081, 1002, 968, 953, 942, 928, 888, 795, 726, 697;
UV (methanol) 239 (9500), 270 (sh. 795), 322 (143) nm.
(b) Syn th esis of 1-(4-F lou r oben zoyl)-2-m eth yla d a m a n -
ta n e (1b). The above compound was synthesized following the
procedure published previously.6b The NMR and mass spectral
data of the intermediates perfectly matched with the literature
reports. The final ketone 1b had the following spectral data,
which is in agreement with the literature data: 1H NMR
(CDCl3, 400 MHz) δ 7.84-7.70 (2H, m), 7.14-6.99 (2H, m),
2.34 (2H, m), 2.19-2.05 (2H, m), 1.90-1.72 (3H, m), 1.72-
1.55 (7H, m), 1.50 (3H, s); 13C NMR (CDCl3, 100 MHz) δ 23.6,
26.9, 27.1, 32.5, 34.2, 34.9, 38.0, 53.0, 114.7 and 115.1 (2J C-F
) 21 Hz), 130.3 and 130.4 (3J C-F ) 8 Hz), 135.0 and 135.0
(4J C-F ) 3 Hz), 161.6 and 166.6 (1J C-F ) 232 Hz), 208.4; LRMS
(EI) m/e (relative intensity) 273 (0.3), 272 (M+, 1.5), 150 (14.2),
149 (100.0), 148 (4.6), 123 (7.3), 121 (1.2), 107 (4.0), 95 (5.0),
93 (4.9), 81 (2.4), 79 (2.1), 67 (1.1); IR cm-1 (KBr pellet) 2921,
2858, 1668, 1598, 1504, 1454, 1354, 1259, 1226, 1160, 1142,
1103, 1084, 970, 954, 940, 851, 821, 769, 759, 608, 543, 492;
UV (methanol) 241 (8900), 333 (70) nm.
(c) Syn th esis of Ch ir a l Ester s of 2-Ben zoyla d a m a n -
ta n e-2-ca r boxylic Acid . Esters of (-)-menthol, (+)-isomen-
thol, S(-)-2-methylbutanol, and (+)-isopino-campheol with
2-benzoyladamantane-2-carboxylic acid were synthesized fol-
lowing the general procedure given below for menthyl ester.
Adamantane-2-carboxaldehyde 20 (6.3 g) was dissolved in
a 250-mL round-bottomed flask using 70 mL of acetone, and
the solution was cooled to 5 °C. A solution consisting of 5.0 g
of CrO3, 20 mL of water, and 8 mL of sulfuric acid was added
dropwise to the cooled solution until the J ones reagent was in
excess. The mixture was allowed to stir at room temperature
for 2.5 h, after which the acetone was removed under reduced
pressure. Cold water (100 mL) was added, and the mixture
was extracted with diethyl ether (3 × 75 mL). The combined
ethereal layers were extracted with 1 N NaOH (5 × 50 mL).
(C6H5)3Cl (19.3 g, 56.3 mmol). The round-bottomed flask was
purged with nitrogen ,and 130 mL of dry diethyl ether was
added. The flask was cooled to 0 °C, and 27 mL of n-
butyllithium (2.5 M solution, 67.2 mmol) was slowly injected
by syringe over 5 min. The mixture changes color from yellow
to red. The scarlet red suspension was stirred for 1 h under a
nitrogen atmosphere. In another round-bottom flask adaman-
tane-2-one 18 was dissolved in 80 mL of dry diethyl ether and
added dropwise to the above via a double-ended needle, and
the mixture was allowed to stir at room temperature for 15 h.
The solution was stirred vigorously while 10 g of anhydrous
zinc chloride (73.4 mmol) was added to complex with the
suspended triphenylphospine oxide. The ether layer was
decanted and evaporated to yield the enol ether 19, which was
hydrolyzed to the aldehyde 20.
The vinyl ether obtained above was dissolved in 90 mL of
diethyl ether. Perchloric acid (70%, 9 mL) and water (5 mL)
were added, and the mixture was refluxed for 1 h, after which
the mixture was poured into water (100 mL). The organic layer
was separated, washed with water, and dried over sodium
sulfate. The solvent was evaporated to yield 6.5 g (78% yield)
of the aldehyde 20, which was used without purification in
the next reaction with the grignard reagent.
The aldehyde obtained above was reacted with phenylmag-
nesium bromide to give the corresponding alcohol. In a dry,
nitrogen-purged round-bottomed flask, 3.0 g (16.5 mmol) of
2-adamantyl aldehyde was dissolved in 75 mL of THF and
cooled in an ice bath. The phenylmagnesium bromide (3.0 M
in ether solution, 27 mL, 80 mmol) was added via a syringe
over 5 min to the ice-cooled solution of the aldehyde. The
mixture was stirred at room temperature for 5 h, after which
saturated ammonium chloride was added very carefully. The
mixture was extracted with water and dried. The solvent was
removed to yield a yellow liquid (4 g, 89% yield) of the alcohol
21, which was purified by column chromatography (20% ethyl
acetate-hexane): 1H NMR (CDCl3, 400 MHz) δ 7.35-7.28 (5H,
m), 4.89-4.86 (1H, d), 2.33 (1H, s), 2.08-2.10 (1H, m), 1.93-
1.86 (5H, m), 1.81-1.21 (9H, m); 13C NMR (CDCl3, 100 MHz)
(18) Corey, E. J .; Suggs, J . W. Tetrahedron Lett. 1975, 31, 2647.
8348 J . Org. Chem., Vol. 67, No. 24, 2002

Yang Photocyclization within Zeolites
1
After washing with ether, the aqueous layer was acidified with
concentrated HCl. The white precipitate was extracted with
ether. After washing with water, drying over sodum sulfate,
and removal of the solvent in vacuo, adamantane-2-carboxylic
acid 23 was left as a white solid (5.9 g, 85%).
Da ta for k eton e 5b: H NMR (CDCl3, 400 MHz) δ 7.88-
7.86 (2H, m), 7.47-7.43 (1H, m), 7.37-7.33 (2H, m), 5.02-
5.01 (1H, m), 2.92-2.90 (2H, m), 2.20-2.19 (1H, m), 1.98-
1.96 (1H, m), 1.90-1.23 (16H, m), 0.94-0.71 (9H, m), 0.62-0.
60 (3H, d); GC-MS (EI+) m/e (relative intensity) 422 (2, M+),
284 (2), 211(1), 163(12.9), 162 (100), 134 (3), 118 (2), 105 (30),
83 (8.6), 77 (13), 55 (11), 41 (7.5); UV (CH3CN) λmax 205, 245,
280 nm.
A 25-mL round-bottomed flask was flame-dried and allowed
to cool with continuous nitrogen flow. The flask was charged
with adamantane-2-carboxylic acid 23 (0.36 g, 2.0 mmol) in
dry methylene chloride (7 mL). Oxalyl chloride (0.35 mL, 4.0
mmol) was added via syringe. After the mixture stirred for 5
min at room temperature, a catalytic amount of dry dimeth-
ylformamide (5 µL) was added. The reaction mixture was
allowed to stir for 2.5 h. Excess oxalyl chloride and solvent
were removed under reduced pressure. The resulting yellow
oil was redissolved in dry methylene chloride (13 mL) and
added via syringe (0.31 mL, 2.2 mmol) in methylene chloride,
maintained in a nitrogen atmosphere at ice-bath temperature.
The mixture was allowed to warm to room temperature and
stirred overnight. The solvent was removed in vacuo, and the
residue was redissolved in 30 mL of diethyl ether and 15 mL
of cold water. The mixture was stirred for a few minutes until
all of the solid residue had dissolved. The ethereal layer was
separated and washed with 5% hydrochloric acid, a 5%
aqueous solution of sodium bicarbonate, water, and a saturated
solution of sodium chloride. After drying over anhydrous
magnesium sulfate, the solvent was removed in vacuo. The
crude product was purified by column chromatography (pe-
troleum ether-diethyl ether, 40:1) to yield 27 as a white solid
(508 mg, 1.6 mmol, 80% yield).
1
Da ta for k eton e 5c: H NMR (CDCl3, 400 MHz) δ 7.82-
7.80 (2H, m), 7.52-7.50 (1H, m), 7.47-7.50 (2H, m), 4.20-
3.88 (2H, ddd), 2.85-2.82 (2H, m), 2.25-2.15 (1H, m), 1.85-
1.18 (14H, m), 0.78-0. 68 (6H, m); 13C NMR (CDCl3, 100 MHz)
δ 200, 172, 138.0, 132, 128.5, 128.2, 70.2, 66.1, 37.6, 34.6 34.3,
34.0, 33.0, 27.0, 26.8, 26.1, 16.5, 11.2; GC-MS (EI+) m/e
(relative intensity) 354 (2, M+), 211 (1.2), 179(1.3), 162(19.6),
133 (3.1), 105 (100), 77 (24.7), 55 (5), 41 (12); UV (CH3CN)
λmax 200, 235, 265 nm.
Da ta for k eton e 5d : GC-MS (EI+) m/e (relative intensity)
420 (M+), 285 (12), 284(13.1), 268(10.9), 267 (42), 266 (7.6),
239 (19.5), 136 (20.6), 121 (11.9), 105 (100), 93 (40), 77 (43.5),
55 (23.9), 41 (34.7); UV (CH3CN) λmax 208, 245, 280, 325 nm.
P r oced u r es for Loa d in g a n d P h otolysis of Ad a m a n -
ta n e Ar yl Keton es 1a , 1b, a n d 5a -d . P h otolysis. All
photolyses were performed by using a 450-W medium-pressure
mercury lamp placed in a water-cooled Pyrex immersion well
(transmits λ > 290 nm). For solution-phase photolysis, the
sample was taken in a Pyrex test tube and dissolved in
methylene chloride-hexane (1:4) solution. The sample was
degassed for 15 min prior to irradiation. A minimum of three
samples were irradiated.
Potassium diisopropylamide-lithium tert-butoxide (KDA)
mixture was prepared following the procedure described by
Ramcher and Koople.19 A flame-dried 50-mL round-bottomed
flask equipped with septum and magnetic stirrer was charged
with potassium tert-butoxide (84 mg, 0.75 mmol) and diiso-
propylamine (0.11 mL, 0.75 mmol) in dry THF (5 mL) under
a nitrogen atmosphere. The flask was cooled to -78 °C, and
n-butyllithium (0.34 mL, 0.62 mmol, 1.6 M solution in hexane,
Aldrich) was added via syringe to form a yellow mixture of
potassium diisopropylamide and lithium tert-butoxide. The
reaction mixture was allowed to stir for 40 min at -78 °C. A
solution of ester 130 (161 mg, 0.5 mmol) in THF (5 mL)
precooled to -78 °C under a nitrogen atmosphere was added
via a double-ended needle. Upon addition the mixture changed
from pale to dark yellow in color. The mixture was stirred for
1 h, and benzoyl chloride (0.17 mL, 1.5 mmol) was added via
syringe. Stirring was continued for 30 min. The reaction was
quenched with 5% HCl, allowed to warm to room temperature,
and diluted with diethyl ether. The layers were separated, and
the aqueous layer was extracted with diethyl ether. The
combined ethereal layers were washed with a saturated
solution of sodium carbonate, water, and a saturated solution
of sodium chloride. After drying over anhyrous magnesium
sulfate the solvent was removed in vacuo to give the crude
product that was purified by column chromatography (petro-
leum ether-diethyl ether, 400:1) to yield the ester 5a as a
viscous oil (171 mg, 0.41 mmol, 81% yield).
Loa d in g, P h otolysis of 2-Ben zoyl-2-m eth yla d a m a n -
ta n e 1a a n d 1b, a n d An a lysis of P h otop r od u cts. In general
samples were prepared under dry conditions. (-)-Ephedrine
(30 mg, 182 mmol) was dissolved in a mixture of methylene
chloride-hexane (1:4). NaY (300 mg), dried at 500 °C, was
added to the above. The slurry was stirred for 8 h, filtered,
and washed with hexane (3 × 5 mL). The zeolite modified with
the chiral inductor was dried under vacuum (3 × 10-3 Torr)
and added to a solution of the adamantyl aryl ketone 1a (5
mg) in methylene chloride-hexane (1:4). The loading level was
maintained at 1 molecule for every supercage for the chiral
inductor and 1 molecule for every 10 supercages for the
substrate. The slurry was stirred for 12 h, filtered, and washed
with hexane (3 × 5 mL). The zeolite complexed with the chiral
inductor and the substrate was transferred to a Pyrex test tube
and irradiated in hexane for 75 min. The products of the
irradiation were extracted with diethyl ether. The ee of the
photoproduct of 1a was determined on the chiral HPLC column
OD (Chiralcel). The enantiomers of the product were resolved
with hexane-iPrOH (99:1), with a flow rate of 0.5 mL/min,
detection at 235 nm. The ee of the photoproduct of 1b was
determined on the chiral GC column Supelco â-dex 350/1701
(10 m, custom-made) (phase:nono-bonded; 50% 2,3-di-o-methyl-
6-o-TBDMS-â-cyclodextrin).
Loa d in g a n d P h otolysis of Ch ir a l Ester s of 2-Ben zoyl-
a d a m a n ta n e-2-ca r boxylic Acid a n d An a lysis of P h oto-
p r od u cts. Esters of (-)-menthol, (+)-isomenthol, S(-)-2-
methylbutanol, and (+)-isopinocampheol with 2-benzoyladaman-
tane-2-carboxylic acid were loaded into MY zeolites and
photolyzed as follows, The experiments were carried out under
dry irradiation conditions as described below. NaY (300 mg),
dried at 500 °C, was taken into 7-8 mL of hexane, and 2 mg
of the adamantyl ketoester was added to it. The slurry was
stirred for 8 h and filtered, and the zeolite loaded with the
compound was vacuum-dried (3 × 10-3 Torr) at 65 °C for 6 h
and irradiated in a Pyrex test tube in dry hexane (450-W
medium-pressure Hg lamp) for 60 min. The products were
extracted from the zeolite with diethyl ether.
1
Da ta for k eton e 5a : H NMR (CDCl3, 400 MHz) δ 7.88-
7.86 (2H, m), 7.47-7.43 (1H, m), 7.37 (2H, m), 4.67-4.23 (1H,
ddd, J ) 10.4 Hz, J ) 4.3 Hz), 2.92-2.90 (2H, m), 2.20-2.19
(1H, m), 2.07-2.04 (1H, m), 1.92-1.32 (16H, m), 0.98-0.71
(9H, m), 0.52-0. 51 (3H, d, J ) 7 Hz); 13C NMR (CDCl3, 100
MHz) δ 199.7, 171.4, 138.0, 131.8, 128.3, 128.0, 75.2, 65.7, 46.6,
40.1, 37.1, 34.3, 34.2, 34.1, 33.8, 33.8, 32.9, 32.8, 31.3, 26.7,
25.4, 22.7, 21.9, 20.6, 15.4; GC-MS (EI+) m/e (relative
intensity) 422 (2, M+), 284 (2), 211(1), 163(12.9), 162 (100),
134 (3), 118 (2), 105 (30), 83 (8.6), 77 (13), 55 (11), 41 (7.5); IR
cm-1 (neat) 3066, 2911, 1718, 1681, 1598, 1580, 1456, 1371,
1198, 1097, 1060, 1039, 1010, 982, 950, 914, 845, 821, 800,
783, 773, 698, 679, 647, 627, 470; UV (n-pentane) λ
(28000), 240 (8400), 275 (1100), 330 (130) nm.
195
max
The de of the photoproduct of 5a was determined on the
GC column SE-30 column (length 30 m, i.d. 0.32 mm, film
thickness 0.25 mm). The de of the photoproduct of 5b was
determined using chiralpak AD column with hexane-iPrOH
(19) Ramcher, S.; Koople, G. J . Org. Chem. 1978, 43, 3794.
J . Org. Chem, Vol. 67, No. 24, 2002 8349

Natarajan et al.
99:1, flow 0.3 mL/min. The de of the photoproduct of 5c was
determined using chiralpak AD column with hexane-iPrOH
99:1, flow 0.2 mL/min. The de of the photoproduct of 5d was
determined using chiralpak AD column with hexane-iPrOH
99:1, flow 0.3 mL/min.
Ch a r a cter iza tion of P h otop r od u cts. Cyclobutanols from
ketones 1a and 1b have been characterized previously, and
our spectral data are in agreement with the literature reports.6
The spectral data of cyclobutanols from ketones 5 were
compared with those from ketones 1. They were identical
excepting for additional 1H NMR peaks due to chiral auxiliary.
Spectra data from 5a and 5c are provided below.
and alkali metal ion Li+ binding ) was carried out using Titan
program version 1.0.5 (Schrodinger Inc., Portland, OR) at the
RB3LYP level. The 6-31G(d) basis set was used for C, H, O,
and Li. Computation on menthyl ester of 2-benzoyladamatane-
2-carboxylic acid (geometry optimization and Li+ cation bind-
ing) was done in the Gaussian-98, A.9 program at the B3LYP
levl; 6-31G(d) basis set was used for C, H, O, Li.10 Frequency
calculations were done at HF level with 3-21G* basis set for
C, H, O, and Li.
Ack n ow led gm en t. V.R. thanks the National Sci-
ence Foundation (CHE-9904187 and CHE-0212042),
and J .R.S. thanks the National Sciences and Engineer-
ing Research Council of Canada for financial support.
Authors thank M. Leibovitch, M. R. Netherton, and A.
Zenova for sharing information on synthesis, product
characterization, and results of solid-state photolysis of
2-benzoyl adamantanes and related systems described
here. V.R. group thanks Drs. J . Chandrasekhar and R.
B. Sunoj for their continued help with computational
work at Tulane.
Da ta for p h otop r od u ct of k eton e 5a : 1H NMR (CDCl3,
400 MHz) δ 7.88-7.86 (2H, m), 7.49-7.45 (1H, m), 7.36-7.32
(2H, m), 4.60-4.52 (1H, ddd, J ) 10.4 Hz, J ) 4.3 Hz), 3.45-
3.42 (1H, m), 2.90-2.88 (3H, m), 1.92-1.32 (16H, m), 1.0-
0.78 (9H, m), 0.63-0. 60 (3H, d); GC-MS (EI+) m/e (relative
intensity) 422 (2.1, M+), 284 (20), 267 (34.4), 266 (10.7), 238-
(18.2), 179 (8.6), 162 (16.1), 134 (43), 106 (10.7), 105 (100), 83
(8.6), 77 (13), 55 (37.6), 41 (23.6).
Da ta for p h otop r od u ct of k eton e 5c: 1H NMR (CDCl3,
400 MHz) δ 8.1-7.90 (2H, m), 7.58-7.56 (1H, m), 7.54-7.50
(2H, m), 3.4-3.2 (2H, ddd), 3.02-2.98 (1H, m), 2.72-2.62 (2H,
m), 2.60-2.58 (1H, m), 2.30-1.22 (13H, m), 0.80-0.76 (3H,
m), 0.72-0. 70 (3H, m); GC-MS (EI+) m/e (relative intensity)
354 (14, M+), 267 (9.7), 266 (17.4), 238 (25), 179 (14), 161 (5.4),
133 (16.3), 105 (100), 91 (20.6), 77 (30.4), 55 (7), 43 (22.8).
Com p u ta tion a l Meth od s Used . Computation on 2-meth-
yl-2-benzoyl adamantane (equilibrium geometry optimization
Su p p or tin g In for m a tion Ava ila ble: Cartesian coordi-
nates of all computed structures. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O0260793
8350 J . Org. Chem., Vol. 67, No. 24, 2002