The influence of chiral auxiliaries is enhanced within zeolites

Article abstract of DOI:10.1016/S0040-4039(00)01459-3

Zeolites significantly enhance the influence of chiral auxiliaries during photochemical reactions. The generality of this phenomenon has been tested with three independent examples. Chiral auxiliaries that lead to 1:1 mixtures of diastereomers in solution

Full text of DOI:10.1016/S0040-4039(00)01459-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8231–8235
The influence of chiral auxiliaries is enhanced within zeolites
Sivaguru Jayaraman,a Sundararajan Uppili,a Arunkumar Natarajan,a Abraham Joy,a
Kenneth C. W. Chong,b Matthew R. Netherton,b Alla Zenova,b J. R. Scheffer*b and
V. Ramamurthya,*
aDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA
bDepartment of Chemistry, University of British Columbia, Vancouver, BC, Canada V6T 1Z1
Received 13 July 2000; accepted 21 August 2000
Abstract
Zeolites significantly enhance the influence of chiral auxiliaries during photochemical reactions. The
generality of this phenomenon has been tested with three independent examples. Chiral auxiliaries that
lead to 1:1 mixtures of diastereomers in solution give products in up to 80% diastereomeric excess in the
presence of faujasite type zeolites. © 2000 Elsevier Science Ltd. All rights reserved.
Asymmetric induction continues to be one of the main concerns of organic chemists. While
the basic rules of asymmetric induction have been reasonably well established for ground state
reactions, the same is not true of photochemical processes.1 Short excited state lifetimes and low
activation energies for reactions in the excited state make manipulation of the diastereomeric
transition states difficult. Nevertheless impressive asymmetric induction has been achieved with
photochemical reactions in the solid state.2 In contrast, asymmetric induction of photochemical
reactions in solution continues to be inefficient under ambient conditions. Among the various
approaches employed to achieve asymmetric induction in solution phase photoreactions, the
‘chiral auxiliary’ strategy (wherein the chiral auxiliary is covalently linked to the reactant
molecule) has been most promising.1,3 By this method, diastereomeric excesses (des) above 90%
have been achieved during addition of olefins to excited enones and other carbonyl and
thiocarbonyl compounds in solution.1,3 We recently showed that moderate levels of asymmetric
induction can be obtained by using zeolites as the reaction medium through the ‘chiral inductor’
approach as well. In this method the chiral inductor is not linked to the reactant molecule.4 For
example, photocyclization of tropolone-2-phenylethyl ether within ephedrine-modified NaY
gave the bicyclo[3.2.0] product in 69% enantiomeric excess (ee), while in hexane/methylene
chloride solution in the presence of ephedrine, a racemic mixture was obtained. This observation
* Corresponding authors. Tel: 504 862 8135; fax: 504 865 5596; e-mail: murthy@tulane.edu
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01459-3

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suggested to us that zeolites could also be used to enhance the influence of covalent chiral
auxiliaries during photochemical reactions. We have tested this possibility with three indepen-
dent photochemical reactions and confirmed that, compared to isotropic solution, zeolites
significantly enhance the influence of a covalent chiral auxiliary. The results of this study are
presented in this letter.
1,2-Diphenylcyclopropane has played an important role in the development of methods of
asymmetric induction in photochemical reactions.5 The highest ee thus far reported during the
photoconversion of the optically inactive cis-1,2-diphenylcyclopropane to the chiral trans-isomer
has been ꢀ10%. cis-1,2-Diphenylcyclopropane was not suitable for the present study since it is
not appreciably converted to the trans-isomer upon irradiation in MY zeolites.6 Therefore we
selected 2b,3b-diphenylcyclopropane-1a-carboxylic acid derivatives as the model (Scheme 1).
Both esters and amides were used. When ethyl ester 1a included in zeolite NaY was irradiated
(450W medium pressure mercury lamp, quartz test tube), the corresponding trans-isomer was
formed within 90 minutes (conversion: 5–20%) as a racemic mixture.7 Of the various chiral
auxiliaries investigated, the results obtained with the menthyl ester 1b and 1-phenylethyl amide
1c are described in detail. Irradiation of 1b and 1c in dichloromethane/hexane solution gave the
corresponding trans-isomers in 4 and 2% de, respectively. In startling contrast, when ester 1b
and amide 1c were included in zeolites and irradiated as solids or hexane slurries, the
corresponding trans-isomers were formed in much higher des. The maximum de for the menthyl
ester 1b was obtained in NaY (LiY: 50; NaY: 55; KY: 30 and RbY: 22%) and for 1-phenylethyl-
amide 1c in LiY (LiY: 80; NaY: 28; KY: 14 and RbY: 5%). The GC traces of the solution and
zeolite irradiations of menthyl ester 1b and 1-phenylethylamide 1c reproduced in Scheme 1
illustrate the remarkable control zeolites exert on the chiral induction process.
Scheme 1. The GC traces for the solution and zeolite irradiations are shown (since the chart speed was faster, the GC
traces for 1b appear broader). For conditions of analysis see reference 7. The first peak from the left is identified as
A
The second photoreaction we have examined is the rearrangement of the achiral 1,2-dihydro-
2,2%-dimethylnaphthalenone derivative 2 to the chiral benzobicyclo[3.1.0]hexenone derivative 3
(Scheme 2).8 As in the case of ester 1a, the chiral inductors menthol and 1-phenylethylamine
failed to give significant ee in product 3a on irradiation of the methyl ester 2a in their presence

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Scheme 2. The GC traces for the solution and zeolite irradiations are shown. For conditions of analysis see reference
7
in dichloromethane solution (<5%) or within NaY. However, when these inductors were
covalently linked to compound 2 as menthyl ester 2b and 1-phenylethylamide 2c, a dramatic
influence on the photorearrangement process within zeolites was observed (450W medium
pressure mercury lamp, uranyl filter; 5 minutes; 30% conversion). Within zeolite KY the des
were 60 and 81%, and once again the extent of de depended on the cation (2b: LiY: 12; NaY:
46; KY: 60; and RbY: 48%; 2c: LiY: 49; NaY: 59; KY: 81; and RbY: 57%).
The third reaction we have explored is the Norrish–Yang reaction of 2-benzoyladamantane-2-
carboxylic acid derivative 4 (Scheme 3).9 The chiral auxiliaries were introduced as ester
functionalities. Irradiation of the menthyl ester 4a and 2-methylbutyl ester 4b in acetonitrile gave
6 as the final product. Phenyl ketone 6 is formed via cyclobutanol 5, a product of a
Scheme 3. The GC and HPLC traces for the solution and zeolite irradiations are shown. For conditions of analysis
see reference 7

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Norrish–Yang reaction. Owing to the photolabile nature of product 6, conversions beyond
15% resulted in secondary products. Therefore all irradiations were limited to ꢀ10% conver-
sion. Irradiation of 4a in acetonitrile resulted in 6a with 22% de. When the same molecule
was included in LiY and irradiated (450W medium pressure mercury lamp, Pyrex filter; 5
minutes; 10% conversion), product 6a was formed in 79% de. It is important to note that the
isomers enhanced in LiY and in acetonitrile differ (Scheme 3). The extent of de varied with
the cation: NaY:62%; and KY:17%. The ester of S-(−)-2-methylbutan-1-ol 4b behaved simi-
larly, resulting in product 6b whose de was significantly improved compared to that observed
in acetonitrile solution (LiY:37; NaY:41 KY:29; RbY:28%).
The three examples provided here, along with our recent report on tropolone-2-methylbutyl
ether (de in solution 0% and in NaY 51%)10 convincingly demonstrate that the influence of a
chiral center present as a chiral auxiliary can be significantly enhanced when the photoreac-
tion is carried out within a zeolite. We have shown examples in which the chiral auxiliary,
with little or no influence in solution, enhances product formation to ꢀ80% de in zeolites.
The observed generality suggests that the phenomenon responsible for the enhanced chiral
induction within zeolites must be independent of the reaction and the chiral auxiliary. Exami-
nation of the zeolite interior (Fig. 1), in which the reactant molecule is expected to be
present, suggests that the most likely factor responsible for the change in de between solution
and zeolite is a difference in conformational preference for the reactant molecule in these two
media. Properties such as intermolecular interactions and the nature and structure of the
reaction cavity, which contribute to the immediate surroundings of a reactant molecule, differ
between solution and zeolites. In solution the intermolecular interactions (with the solvent
molecules) are expected to be weak and transient, whereas they are likely to be strong and
more permanent within zeolites.11 Furthermore, while the ‘reaction cavity’ in solution is soft
and time-dependent, that in zeolites is hard and relatively time independent. We are currently
examining the conformational differences of the reactants described here by semi-empirical
theoretical calculations and solid state NMR.
Figure 1. The internal structure of a zeolite supercage. The four windows that connect adjacent supercages are
marked. The dark circles represent the Type II cations. Darker lines represents the front atoms and the lighter lines
represents the ones at the back

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Acknowledgements
V.R. thanks the National Science Foundation (CHE-9904187), and J.R.S. the Petroleum
Research Fund, administered by the American Chemical Society and the Natural Sciences and
Engineering Research Council of Canada for support of this research.
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