Stereoselective photooxidation of enecarbamates: Reactivity of ozone vs singlet oxygen

Article abstract of DOI:10.1021/ol0502230

(Chemical Equation Presented) Oxazolidinone-functionalized enecarbamates show contrasting behavior upon oxidation by singlet oxygen and by ozone. The observed stereoselectivity difference indicates that the oxidation with ozone is subject to classic steri

Full text of DOI:10.1021/ol0502230

ORGANIC
LETTERS
2005
Vol. 7, No. 11
2089-2092
Stereoselective Photooxidation of
Enecarbamates: Reactivity of Ozone vs
Singlet Oxygen
J. Sivaguru,† Hideaki Saito,†,‡ Thomas Poon,§ Toma Omonuwa,† Roberto Franz,†
|
Steffen Jockusch,† Catherine Hooper,§ Yoshihisa Inoue,‡ 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, ICORP (JST)
and Department of Molecular Chemistry, Osaka UniVersity, 2-1 Yamada-oka,
Suita 565-0871, Japan, Institut fu¨r Organische Chemie, UniVersita¨t Wu¨rzburg,
97074 Wu¨rzburg, Germany, and Department of Chemistry, UniVersity of Puerto Rico,
Rio Piedras, PR 00931
njt3@columbia.edu
Received February 2, 2005
ABSTRACT
Oxazolidinone-functionalized enecarbamates show contrasting behavior upon oxidation by singlet oxygen and by ozone. The observed
stereoselectivity difference indicates that the oxidation with ozone is subject to classic steric effects, whereas the very high selectivity in the
photooxidation with singlet oxygen is derived from vibrational deactivation.
Understanding the mechanisms of organic reactions has led
to vast advances in the area of asymmetric processes.1
Unfortunately, asymmetric photoreactions2 have not enjoyed
the same level of attention as asymmetric thermal reactions.
Recently, we reported a very high stereoselectivity in the
photooxidation3,4 of oxazolidinone-derived enecarbamates
(Scheme 1) with singlet oxygen5 (1O2), both in solution3 and
1
Scheme 1. Oxidation of (E)-/(Z)-Enecarbamates by O2/O3
† Columbia University.
‡ Osaka University.
§ Claremont McKenna, Pitzer, and Scripps Colleges.
| Universita¨t Wu¨rzburg and University of Puerto Rico.
(1) (a) Taylor, M. S.; Jacobsen, E. N. Proc. Natl. Acad. Sci. 2004, 101,
5368-5373. (b) Evans, D. A. In Asymmetric Synthesis. Stereodifferentiating
Reactions; Morrison, J. D., Ed.; Academic Press: New York; 1984; Vol.
3, Part B, p 1. (c) Ojima, I. In AdVances in Asymmetric Synthesis; Hassner,
A., Ed.; Jai Press, Inc.: Greenwich, CT, 1995; p 95.
in organized media.4 To elucidate the factors responsible for
the high stereocontrol in this photooxidation, we have
10.1021/ol0502230 CCC: $30.25
© 2005 American Chemical Society
Published on Web 04/23/2005

investigated the reactivity of ozone6 (O3) with oxazolidinone-
functionalized enecarbamates. The selectivity during pho-
tooxidation by O2 was shown to depend on the alkene
b
Table 1. Oxidation of the (E)- and (Z)-Enecarbamatesa by O3
sub- % ee % con-
stratea solvent (°C) MDBc versiond se ∆∆H‡ f ∆∆S‡ f
1
T
geometry;3,4 the (E)-isomer gives higher selectivity than the
corresponding (Z)-isomer in isotropic media.3 By investigat-
ing the reactivity of O3 with oxazolidinone-derived enecar-
bamates, we expected to gain insight into the high stereo-
E1
CD2Cl2
20 22 (S)
-15 24 (S)
-45 16 (S)
-70 18 (S)
20 18 (S)
6
15
18
27
12
17
25
4
1.6
1.7
1.4
1.5
0.16
1.49
1
selectivity observed with O2, in view of the facts that (i)
O3 and 1O2 are electrophilically similar in nature,5-7 (ii) the
E1
E1
CDCl3
1.5 -0.48 -0.97
1
products upon oxidation with O2 and O3 are the same
-15 20 (S)
-70 29 (S)
1.6
2.0
1.1
1.1
1.0
1.1
(Scheme 1), and (iii) the importance of radiationless
deactiVation (physical quenching) may be assessed during
the oxidation process because O3 is a reactive ground-state
CD3OD
20
-15
-45
-70
4 (S)
2 (S)
0
0.12
0.16
6
4
1
species compared to O2, an excited-state molecule.
4 (S)
5
Z1
Z2
CD2Cl2
CD2Cl2
20 31 (R)
-15 30 (R)
-78 36 (R)
20 33 (S)
20 27 (S)
-15 38 (S)
-15 12 (S)
10
12
9
6
9
2.0 -0.14
1.9
2.2
0.79
2.98
ln(kR/kS) ) ln[(100 + % ee)/(100 - % ee)]
ln(kR/kS) ) ∆∆S‡R-S/R - ∆∆H‡R-S/RT
(1)
(2)
2.0
1.8
2.3
1.3
1.2
2.2
1.1
1.6
1.4
1.5
0.6
kR ln[1 - C(1 + eeMDB)]
7
s )
)
(3)
20
27
9
36
16
17
14
3
kS
ln[1 - C(1 - eeMDB)]
-45
-70 36 (S)
-70 4 (S)
6 (S)
where C in eq 3 is the conversion and eeMDB is the ee value
of the MDB product.
Z2
Z2
CDCl3
20 20 (S)
-15 16 (S)
-70 18 (S)
20 20 (S)
-15 21 (S)
-45 22 (S)
-70 22 (S)
0.08
1.03
0.62
The epimeric pairs of oxazolidinone-derived (E)- and (Z)-
enecarbamates were oxidized with O3 in three different
solvents (CD2Cl2, CDCl3, and CD3OD) at various temper-
atures (Table 1). The conversion was kept low to avoid side
reactions,6 and the enantiomeric excess (ee) was obtained
by GC analysis of the methyldesoxybenzoin (MDB) product
on a chiral stationary phase (Scheme 1). Inspection of Table
1 reveals the following features: (i) The same enantiomer
of the MDB is enhanced upon varying the solvent, but a
noticeable change in the ee values is observed at the same
temperature for both (E)- and (Z)-enecarbamates; for ex-
ample, at -70 °C, the ee values for O3 oxidation of E1 in
CD3OD is 4%; in CD2Cl2, 18%; and in CDCl3, 29%. (ii)
The sense of the enhanced MDB enantiomer depends on the
configuration at the C-4 position of the oxazolidinone ring
as well as the alkene geometry; for example, E1 gave the
(S)-MDB in excess, whereas the corresponding (Z)-isomer
CD3OD
1.5 -0.05
4
16
7
1.5
1.6
1.6
a A ca. 50/50 mixture of diastereomers (total concentration of 2.3 ×
10-3 M) was used. b Procedure given in Supporting Information. c Average
of three runs; error (6%. d Conversion monitored by 1H NMR spectroscopy
(see Supporting Information); the conversion was kept low to prevent side
reactions (ref 6). e From eq 3. f From eqs 1 and 2. ∆∆Hq given in (kcal
mol-1); ∆∆Sq given in (cal mol-1 K-1).
(Z1) gave (R)-MDB in excess. (iii) The observed ee value
depends on the extent of conversion, i.e., ee values were
moderate at low conversions and small at high conversions.
(iv) The same MDB enantiomer is enhanced upon varying
the temperature. (v) The change of the configuration at the
C-4 position of the oxazolidinone reverses the sense of the
MDB enantiomer to the same extent (Figure 1).
(2) (a) Inoue, Y.; Ramamurthy, V. Chiral Photochemistry; Marcel
Dekker: New York, 2004. (b) Lewis, T. J.; Randall, L. H.; Rettig, S. J.;
Scheffer, J. R.; Trotter, J.; Wu, C.-H. J. Am. Chem. Soc. 1996, 118, 6167.
(c) Leibovitch, M.; Olovsson, G.; Sundarababu, G.; Ramamurthy, V.;
Scheffer, J. R.; Trotter, J. J. Am. Chem. Soc. 1996, 118, 1219. (d) Chong,
K. C. W.; Sivaguru, J.; Shichi, T.; Yoshimi, Y.; Ramamurthy, V.; Scheffer,
J. R. J. Am. Chem. Soc. 2002, 124, 2858-2859.
(3) Poon, T.; Sivaguru, J.; Franz, R.; Jockusch, S.; Martinez, C.;
Washington, I.; Adam, W.; Inoue, Y.; Turro, N. J. J. Am. Chem. Soc. 2004,
126, 10498-10499.
(4) Sivaguru, J.; Poon, T.; Franz, R.; Jockusch, S.; Adam, W.; Turro, N.
J. J. Am. Chem. Soc. 2004, 126, 10816-10817.
(5) (a) Wasserman, H. H.; Murray, R. W., Eds.; Singlet Oxygen;
Academic: New York; 1979. (b) Frimer, A. A., Ed. Singlet Oxygen; CRC:
Boca Raton; 1985; Vols. 1-4. (c) Gollnick, K.; Kuhn, H. J. Singlet Oxygen;
Wasserman, H. H.; Murray, R. W.; Eds.; Academic: New York, 1979. (d)
Foote, C. S. Acc. Chem. Res. 1968, 1, 104. (e) Gollnik, K. AdV. Chem.
1968, 77, 78.
(6) Bailey, P. S. Ozonation in Organic Chemistry; New York, 1978; Vols.
1 and 2.
(7) (a) Wadt, W. R.; Goddard, W. A., III. J. Am. Chem. Soc. 1975, 97,
3004-3021. (b) Goddard, W. A., III; Dunning, T. J., Jr.; Hunt, W. J.; Hay,
P. J. Acc. Chem. Res. 1973, 6, 368-376.
Figure 1. GC traces of product MDB. Opposite senses of ee were
observed in the ozonolysis of Z1 (B) and Z2 (A) due to the opposite
configuration at the C-4 position of the oxazolidinone.
2090
Org. Lett., Vol. 7, No. 11, 2005

related by eqs 1 and 2.8 Consequently, the large contribution
from the differential activation parameters for the 1O2 oxida-
tion (Table 2) suggests that the transition state is conforma-
tionally flexible and its solvation-desolvation behavior is
crucial. Expectedly, the temperature and solvent variations
influence the stereodifferentiating step.8 Enthalpic control
applies when the stereoselectivity is enhanced upon decreas-
ing the temperature, a phenomenon common to many thermal
asymmetric reactions.9 In contrast, the low contribution from
the differential activation parameters for the O3 oxidation
indicates that the transition state is more rigid and is not
influenced by the variation of the external factors (solvent/
temperature) of the system. Expectedly, there is no noticeable
change in the extent of the ee values, and the sense of the
enhanced enantiomer remains the same upon oxidation by
O3.
As mentioned above, the ee value depends on the extent
of conversion. The ratio of the rates of formation (relative
rates) of the enantiomeric products may be computed from
the observed ee value at a given conversion by means of eq
3, where kR/kS is s, the stereoselectivity factor.10 Inspection
of Table 1 shows that the s factor at best is about 2 for
oxidation of enecarbamates by O3. The low s factor will lead
to a wide variation in the ee values at different converisons,10
as observed for the O3 oxidation, for which the ee values
are moderate at low and small at high conversions. For
example, 36% ee was observed at 9% conversion and only
4% ee at 36% conversion for the oxidation of Z2 by O3 in
CD2Cl2 at -70 °C. The consequence of the difference in
the s factors in the oxidation by O3 and 1O2 is best illustrated
in Figure 3.10 Under identical conditions, the ee value is 97%
Figure 2. Representative GC traces of product MDB for the
oxidation of E1 by O2 (A) and O3 (B) in CD2Cl2.
1
It is evident from Table 1 that there is no solvent or tem-
perature dependence of the ee values for (E)-enecarbamates
upon oxidation with O3, which is in sharp contrast to the
1
photooxidation3 with O2 (Table 2; Figure 2). Clearly, the
extent of stereoselectivity in the oxidation of E1 with O3
(Table 1) differs from that of 1O2 (Table 2). Further, the (Z)-
enecarbamates do not show any solvent or temperature
dependence upon oxidation with O3, a result similar to the
1O2 oxidation.3 To understand the difference in the behavior
of the oxazolidinone-functionalized enecarbamates toward
1
the oxidation of O3 and O2, we computed the differential
activation enthalpy (∆∆H‡) and entropy (∆∆S‡) values,
which are directly related to the ee values through eqs 1 and
2.8 These data are listed in Tables 1 and 2, which reveal
that there is no significant difference in the activation
parameters for the oxidation of the (E)- and (Z)-enecarbam-
ates with O3. The sharp contrast in the differential activation
parameters for the oxidation of E1 by O3 and 1O2 is revealing
(Tables 1 and 2); for example, in the oxidation of E1 in CD2-
Cl2, the ∆∆S‡ and ∆∆H‡ values for O3 are 1.49 cal mol-1
K-1 and 0.16 kcal mol-1, respectively, compared to -15 cal
mol-1 K-1 and -4.0 kcal mol-1 for 1O2. Thus, the ee value of
the MDB product is a critical balance of the enthalpy (molec-
ular) and entropy (enVironmental) terms, which are inter-
1
3
Table 2. Photooxidation of the (E)-Enecarbamate by O2
sub- % ee % con-
stratea solvent (°C) MDBb versionb,c sd ∆∆H‡ e ∆∆S‡
T
e
E1
CD2Cl2
20 34 (S)
-20 27 (R)
-60 74 (R)
50 8 (S)
25
65
31
5
17
37
43
30
34
17
12
8
2.3 -4.0 -15
2.7
9.2
1.2 -4.5 -14
5.0
Figure 3. GC traces of product MDB for the oxidation of E1 by
O3 and O2 at -70 °C in CD3OD and the plot of % ee versus %
conversion (simulated from eq 3; ref 10d) to illustrate the
1
E1
CDCl3
consequence of the difference in the s factors.
18 63 (R)
-15 78 (R)
-40 88 (R)
50 70 (R)
13
31
7.6 -2.8
1
for the O2 oxidation (s factor of 72) compared to only 4%
E1
CD3OD
-4.9
for the O3 oxidation (s factor of about 1.1).
18 85 (R)
19
23
37
72
It is evident from Table 1 that both (E)- and (Z)-ene-
carbamates give only moderate ee values in the O3 oxidation.
In general, the (Z)-isomers display comparable or higher
-15 90 (R)
-40 94 (R)
-70 97 (R)
a A ca. 50/50 mixture of diastereomers (total concentration 3.0 × 10-3
M) in an NMR tube under O2 pressure was used, with methylene blue (3.7
× 10-4 M) as a sensitizer. b Determined by GC analysis. c Determined by
1H NMR spectroscopy. d From eq 3. e From eqs 1 and 2. ∆∆Hq given in
(kcal mol-1); ∆∆Sq given in (cal mol-1 K-1).
(8) (a) Inoue, Y. Chem. ReV. 1992, 92, 741-70. (b) Buschmann, H.;
Scharf, H.-D.; Hoffmann, N.; Esser, P. Angew. Chem., Int. Ed. Engl. 1991,
30, 477-515. (c) Otera, J.; Sakamoto, K.; Tsukamoto, T.; Orita, A.
Tetrahedron Lett. 1998, 39, 3201.
(9) Leffler, J. E. J. Org. Chem. 1955, 20, 1202.
Org. Lett., Vol. 7, No. 11, 2005
2091

stereoselectivity than the corresponding E isomers, which is
1
in contrast to the observed trend of O2, for which the E
Scheme 2. Oxidation of Z1 by with Triphenyl Phosphite
Ozonide and GC Traces Comparison of (Chiral Stationary
Phase) O3 (A) and by P(OPh)3O3 (B) Oxidation of Z1.
isomer exhibits a very high stereoselectivity (ee >97%)
compared to the (Z)-isomer.3 We speculate that the steric
hindrance experienced by O3 is reflected in the observed
selectivity. As shown in Figure 4B,11 the approach of O3
effects, dipole-induced interactions of the oxidizing species
with the enecarbamates may significantly differ to result in
a different stereoselectivity.
1
The high stereoselectivity observed for O2 (∼97% ee at
-70 °C; CD3OD; Table 2), relates presumably to its
electronically excited nature, since it may be vibrationally
deactivated on encountering C-H bonds.3,5,12 Thus, the
productive chemical pathway is in competition with the
unproductive physical quenching process through deactiva-
Figure 4. Control of the oxidant approach through deactivation
and steric effects for O2 (A) and O3 (B).
1
1
tion by C-H bonds. The oxidation efficiency of O2 is,
onto the double bond from the bottom is hindered by the
isopropyl group, such that O3 is forced to come in from the
top. Moreover, enrichment of the MDB enantiomer depends
on the configuration at the C-3′ position (Figure 4).12 For
example, in the case of Z1, the (4R,3′R)-(Z)-isomer is more
reactive than the (4R,3′S)-(Z)-diastereomer, which affords
(R)-MDB in excess (Figure 4).
therefore, determined by which of the two processes domi-
nates. In previous quenching studies on oxazolidinone-
derived enecarbamates, we demonstrated that the major
pathway is unproductive physical quenching rather than the
useful chemical mode.12 The isopropyl group at the C-4
position of the oxazolidinone chiral auxiliary is apparently
1
responsible for the vibrational deactivation of O2, since it
If steric effects play a dominant role in the O3 oxidation,
then the observed ee values should be higher when a bulky
oxidant is employed. This exception was tested with triphenyl
phosphite ozonide (Scheme 2), which is reported to undergo
direct addition to alkenes through a perepoxide-like transition
state at -70 °C.13 As shown in Scheme 2, an ee value of
83% ((R)-MDB) was observed with Z1 upon triphenyl
phosphite ozonide [P(OPh)3O3] oxidation,13 compared to an
ee value of only 36% ((R)-MDB) with O3. Besides steric
abundantly furnishes C-H bonds. Evidently, a process that
leads to a high stereoselectivity in the product formation must
be void of such vibrational deactivation. We are currently
examining the deuteration of the substrates at the C-4 and
C-3′ stereogenic centers to better understand the high
1
stereoselectivity displayed by O2.
Acknowledgment. The authors at Columbia thank the NSF
(CHE 01-10655 and CHE-04-15516) for generous support
of this research. W.A. gratefully acknowledges the financial
support from the Deutsche Forschungsgemainschaft, Alex-
ander von Humboldt-Stiftung, and the Fonds der Chemischen
Industrie. T.P. acknowledges the support of the W. M. Keck
Foundation. T.O. thanks the NSF-REU program for a
summer research fellowship. H.S. gratefully acknowledges
a JSPS research fellowship (08384) for young scientists.
(10) (a) Keith, J. M.; Larrow, J. F.; Jacobsen, E. N. AdV. Synth. Catal.
2001, 343, 5-26. (b) Kagan, H. B.; Fiaud, J. C. Top. Stereochem. 1988,
18, 249-330. (c) Martin, V. S.; Woodward, S. S.; Katsuki, T.; Yamada,
Y.; Ikeda, M.; Sharpless, K. B. J. Am. Chem. Soc. 1981, 103, 6237. (d)
Ching, S. C.; Fujimoto, Y.; Girdaukas, G.; Sih, C. J. J. Am. Chem. Soc.
1982, 104 (25), 7294-7299.
(11) Structure of the (Z)-isomer was obtained by crystallography; see:
Adam, W.; Bosio, S. G.; Turro, N. J.; Wolff, B. T. J. Org. Chem. 2004,
69, 1704.
(12) Poon, T.; Turro, N. J.; Chapman, J.; Lakshminarasimhan, P.; Lei,
X.; Jockusch, S.; Franz, R.; Washington, I.; Adam, W.; Bosio, S. G. Org.
Lett. 2003, 5, 4951-4953.
(13) (a) Mori, A.; Abe, M.; Nojima, M. J. Org. Chem. 2001, 66, 3548.
(b) Stephenson, L. M.; Zielinski, M. B. J. Am. Chem. Soc. 1982, 104, 5819.
(c) Above -30 °C, the ozonide liberates 1O2, while at lower temperatures,
the ozonide itself is an oxidant (ref 13a).
Supporting Information Available: Reaction procedure,
analysis conditions, and calculation of differential activation
parameters. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL0502230
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Org. Lett., Vol. 7, No. 11, 2005