Stereocontrol within confined spaces: Enantioselective photooxidation of enecarbamates inside zeolite supercages

Article abstract of DOI:10.1021/ja046115a

Dye-exchanged Y zeolite is shown to be an effective medium to control the stereoselectivity in the photooxygenation of chiral oxazolidinone-functionalized Z/E-1 enecarbamates. An enantioselectivity (ee) as high as 80% was observed in the methyldesoxybenzo

Full text of DOI:10.1021/ja046115a

Published on Web 08/11/2004
Stereocontrol within Confined Spaces: Enantioselective Photooxidation of
Enecarbamates Inside Zeolite Supercages
J. Sivaguru,† Thomas Poon,‡ Roberto Franz,† Steffen Jockusch,† Waldemar Adam,§ and
Nicholas J. Turro†,*
Department of Chemistry and Department of Chemical Engineering, Columbia UniVersity, 3000 Broadway,
Mail Code 3119, New York, New York 10027, Joint Science Department, W.M. Keck Science Center,
925 North Mills AVenue, Claremont McKenna, Pitzer, and Scripps Colleges, Claremont, California 91711,
Department of Chemistry, UniVersity of Puerto Rico, Rio Piedras, Puerto Rico 00931, and Institut fu¨r Organische
Chemie, UniVersita¨t Wu¨rzburg, Am Hubland, D-97074 Wu¨rzburg Germany
Received June 30, 2004; E-mail: njt3@columbia.edu
Scheme 1. The Enantioselective Formation of Methyl-
desoxybenzoin (MDB) in the Photooxidation of the Enecarbamates
Z/E-1 Inside Methylene-Blue-Exchanged MY Zeolites
With Nature as role model, chemists have utilized confined media
to achieve selectivity in chemical reactions.1 Zeolites have been
employed to control the outcome of photoreactions2 by manipulating
the spatial requirement of the excited states and reactive intermedi-
ates that are involved. Chirally modified zeolites have been shown
to be effective in achieving high stereoselectivity in photoreactions.3
Here we report the high chiral induction within confined spaces,
viz. zeolite Y supercages, during the photooxidation of the
enecarbamates4 Z/E-1 in zeolite Y supercages5 (Scheme 1). One
of the important features of Y-type zeolites is the presence of
exchangeable cations (alkali/alkaline earth metal cations),6 which
may be readily replaced by cationic dyes7 such as the singlet-oxygen
sensitizer methylene blue.8
Table 1. Enantioselective Photooxygenation of Z/E-1 Inside
Zeolite
hν
%
Oxazolidinone-substituted chiral enecarbamates Z/E-1 are ver-
satile substrates for the study of conformational, electronic, ste-
reoelectronic, and steric effects on the stereoselectivity in the
oxidation of the alkene functionality.4 For example, an enantiomeric
excess (ee) of 97% in the methyldesoxybenzoin (MDB) product
was observed at -70 °C during the photooxidation of the E-1
isomer in methanol-d4.9 This photooxidation in solution was shown
to depend on the configuration of the double bond; the E
diastereomer gave consistently higher stereoselectivity than the
corresponding Z isomer. In fact, even at very low temperatures,
only a modest enantioselectivity (ee) was achieved in the MDB
product for the readily synthesized Z isomer.4,9 Moreover, a very
low conversion (<3%) and the poor mass balance (<35%) was
obtained in the photooxidation of the Z/E-1 diastereomers inside a
cation-exchanged Y zeolite without 1O2 sensitizer.4b Consequently,
we decided to employ dye-exchanged Y zeolites8 to enhance the
efficiency of generating singlet oxygen and thereby provide bona
fide photooxygenation conditions. For this purpose, we chose
methylene blue as 1O2 sensitizer, to probe the efficacy of asymmetric
induction by the oxazolidinone chiral auxiliary in the photooxy-
genation of the Z/E-1 diastereomers within zeolite supercages.
The Z-4(R)-3′(R/S)-1 (or Z-4(S)-3′(R/S)-1) diastereomeric pair
was irradiated (<500 nm cutoff) in the methylene blue (MB)
exchanged NaY zeolite (NaY-MB) under oxygen-saturated atmo-
sphere to give the chiral MDB product in good yield and high
stereoselectivity10 (cf. Table 1 and Figure 1). At room temperature
an ee value of 80% for the R-MDB product (entry 3) was observed
upon irradiation of Z-4(S)-3′(R/S)-1 inside NaY-MB, compared to
only 11% ee in CDCl3 solvent (entry 1). The optical antipodes (R
and S) at the C4 position of the oxazolidinone chiral auxiliary gave
the opposite enantiomer of MDB (entries 3 and 4) with nearly the
(time,
min)
%
convn
mass
balance
MDB-3
a
c
c,d
medium
enecarbamateb
%eee
CDCl3
CDCl3
Z-4(S)-3′(R/S)
Z-4(R)-3′(R/S)
Z-4(S)-3′(R/S)
Z-4(R)-3′(R/S)
E-4(S)-3′(R/S)
E-4(R)-3′(R/S)
E-4(S)-3′(R/S)
E-4(R)-3′(R/S)
20
20
10
10
20
20
10
10
47
49
41
49
50
47
31
33
96
94
86
89
95
92
75
71
11(S)
27(R)
80(R)
71(S)
40(S)
55(R)
62(S)
63(R)
NaY-MB
NaY-MB
CDCl3
CDCl3
NaY-MB
NaY-MB
a Entries 3, 4, 7, and 8 are methylene-blue-exchanged MY zeolite,
prepared as reported in ref 8; the methylene blue loading is one molecule
per 150 supercages. b The enecarbamates 1 were loaded as a 50:50 mixture
of 3′(R/S) diastereomers, one molecule per 15 supercages (low loading level
of enecarbamates ∼3 mg was kept to establish the concept. Higher loading
levels (gram scale, possible in preparative scale irradations)).13 c Conversion
and mass balance were determined by using 4,4′-di-tert-butylbiphenyl as
calibration standard on an achiral stationary phase (Varian GC 3900; Varian
Factor-4 VG-1ms column); values are averages of three runs, the error is
within (5%. d The mass balance without irradiation (thermal control) in
NaY is 90% for Z-1 and 83% for E-1. e Analyzed by GC on a chiral
stationary phase (Varian GC 3900; Varian CP-Chirasil-DEX CB); values
are within (5% error.
same extent of asymmetric induction, indication that the system is
well behaved inside zeolites.
The time-dependent irradiation of Z-4(R)-3′(R/S)-1 inside NaY-
MB showed that the enantioselectivity was independent, but the
mass balance was dependent on the irradiation time (cf. Table S-1,
ref 10). High mass balance was observed for short irradiation times
(<10 min), but on prolonged irradiation, the mass balance
decreased, presumably due to side reactions.10,11
To investigate the influence of the Z/E alkene geometry, the
corresponding E-1 isomer was examined, since in solution9 (entries
5 and 6, Table 1), it gave a higher enantioselectivity than the Z-1
isomer. Photooxygenation of E-4(R)-3′(R/S)-1 within NaY-MB gave
63% ee R-MDB (entry 8); as expected, the E-4(S)-3′(R/S) dia-
† Columbia University.
‡ Claremont McKenna, Pitzer, and Scripps Colleges.
§ University of Puerto Rico and Universita¨t Wu¨rzburg.
9
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J. AM. CHEM. SOC. 2004, 126, 10816-10817
10.1021/ja046115a CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Figure 1. GC traces of the methyldesoxybenzoin (MDB) product, obtained
in the photooxygenation of the Z-1 (left) and E-1 (right) within methylene-
blue-exchanged NaY zeolite.
stereomer (optical antipode at the C4 position of the oxazolidinone
chiral auxiliary) gave the opposite isomer S-MDB (entry 7). As
anticipated,10 this shows that the presence of the chiral center at
position C4 is critical for achieving the high enantioselectivity.
Replacement of the isopropyl group with hydrogen at the C4
position in the oxazolidinone ring gave racemic MDB.10
The effect of the cation3 in the photooxygenation of the E/Z-1
was examined with the MB-exchanged LiY zeolite (LiY-MB). The
same enantiomer of the MDB product, the one preferred inside
NaY-MB, was enhanced within LiY-MB;10 an ee value of 35%
was determined (Figure S6; ref 10).12 The decrease of the ee value
inside LiY-MB may be due to a combination of larger available
volume within the supercage5,6 and the residual water molecules
present inside LiY in view of its high charge density. (Decomposi-
tion of organic dyes at high temperatures prevents complete removal
of water from dye loaded-MY zeolite.)8a
Figure 2. Transition structures proposed for the 1O2 attack in the
photooxygenation of the Z/E-1 enecarbamates in solution [Z/E(A)] and inside
MB-exchanged NaY zeolite [Z/E(B,C)].
Acknowledgment. We at Columbia thank the NSF (CHE 01-
10655) for generous support of this research. T.P. acknowledges
the support of the W.M. Keck Foundation. W.A. gratefully apprec-
iates financing by the Deutsche Forschungsgemeinschaft, the Fonds
der Chemischen Industrie, and the Alexander von Humboldt-Stiftung.
Supporting Information Available: Experimental conditions,
analysis procedures, GC traces, table for time dependence and control
study with the 4-H-oxazolidinone derivative and the studies within LiY-
MB. This material is available free of charge at http://pubs.acs.org.
Our unprecedented results (Table 1, Figure 1) definitively
demonstrate that the sense of the stereoselectivity in the MDB
formation (R or S) depends on the configuration (4R or 4S) of the
oxazolidinone chiral auxiliary, whereas the extent of asymmetric
induction is controlled by the Z/E alkene geometry. For example,
the Z-4(S)-3′(R/S) diastereomeric pair affords the R-MDB product
in 80% ee, whereas the corresponding E-4(S)-3′(R/S)-1 leads to
S-MDB in 62% ee. Mechanistically more revealing is the fact that
in the solution versus zeolite medium, the extent of stereocontrol
is substantially more differentiated for the Z isomers than for the
E isomers. Previously, we had recognized the higher stereochemical
steering in the oxidation of the E- versus the Z-configured
enecarbamates 1, which presumably rests on the higher conforma-
tional flexibility of the E diastereomers in isotropic media.4c,9 We
suspect that the more rigid structural features of the Z isomer are
beneficially utilized in the confined space of the zeolite to align
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