The endocyclic restriction test: Oxygen transfer from N-sulfonyl oxaziridines to alkenes

Article abstract of DOI:10.1021/ol990969w

(formula presented) The transition state for the transfer of oxygen from N-sulfonyl oxaziridines to alkenes has been investigated experimentally using the endocyclic restriction test. Molecules containing oxaziridines and alkenes were prepared and the abi

Full text of DOI:10.1021/ol990969w

ORGANIC
LETTERS
1999
Vol. 1, No. 9
1415-1417
The Endocyclic Restriction Test:
Oxygen Transfer from N-Sulfonyl
Oxaziridines to Alkenes
David R. Anderson, Keith W. Woods, and Peter Beak*
Department of Chemistry, UniVersity of Illinois at Urbana-Champaign,
Urbana, Illinois 61801
beak@scs.uiuc.edu
Received August 20, 1999
ABSTRACT
The transition state for the transfer of oxygen from N-sulfonyl oxaziridines to alkenes has been investigated experimentally using the endocyclic
restriction test. Molecules containing oxaziridines and alkenes were prepared and the ability of each system to intramolecularly transfer
oxygen was evaluated. The results are consistent with a transition state in which N−O bond cleavage is more advanced than C−O bond
cleavage.
N-Sulfonyl oxaziridines are often the oxidants of choice for
transfers of oxygen to carbanions, sulfides, disulfides,
enolates, selenides, and alkenes.1 Seminal work by Davis
and co-workers has led to the development and wide
application of these compounds as “Davis reagents”.1 The
mechanism of oxygen transfer has been the subject of
experimental2 and theoretical3 investigations. When neutral
nucleophiles are used, the transfer of oxygen is suggested
to be a concerted process with simultaneous breaking of the
N-O and C-O bonds of the oxaziridine in the transtion
state.2b However, Evans, Davis, and Dmitrienko have
reported reactions which they interpret as being consistent
with the N-O bond of the oxaziridine breaking before the
C-O bond when carbanions2a,4 and enamines5 are oxidized.
We report determination of the location of atoms in the
transition state for transfer of oxygen from N-sulfonyl
oxaziridines to a carbon-carbon double bond through use
6
of the endocyclic restriction test.
The transition-state structures proposed for concerted
oxygen transfer from the oxaziridine to a nucleophile are
depicted in Figure 1. In 1a, the nucleophile is represented
(1) For a reviews of N-sulfonyl oxaziridines, see: Davis, F. A.; Sheppard,
A. C. Tetrahedron 1989, 45, 5703. Davis, F. A.; Chen, B.-C. Chem ReV.
1992, 92, 919.
(2) (a) Davis, F. A.; Wei, J.; Sheppard, A. C.; Gubernick, S. Tetrahedron
Lett. 1987, 28, 5115. (b) Davis, F. A.; Billmers, J. M.; Gosinak, D. J.;
Towson, J. C.; Bach R. D. J. Org. Chem. 1986, 45, 4240. (c) Knipe, A. C.;
McAuley, I. E.; Khandelwal, Y.; Kansal, V. K. Tetrahedron Lett. 1984,
25, 1411.
Figure 1. Hypothetical transition states for oxygen transfer of
N-sulfonyl oxaziridines to nucleophiles.
(3) (a) Bach, R. D.; Andres, J. L.; Davis, F. A. J. Org. Chem. 1992, 57,
613. (b) Bach, R. D.; Coddens, B. A.; McDouall, J. J. W.; Schlegel, H. B.;
Davis, F. A. J. Org. Chem. 1990, 55, 3325. (c) Bach, R. D.; Wolber, G. J.
J. Am. Chem. Soc. 1984, 106, 1410.
as attacking the oxygen atom with symmetrical C-O and
N-O bond breakage. An alternative transition-state model,
where the N-O bond breaking is more advanced than the
10.1021/ol990969w CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/01/1999

C-O bond cleavage, is shown in 1b. In this alternative
model, the nucleophile attacks the oxygen atom of the
oxaziridine on the backside of the N-O bond similar to an
SN2 displacement at oxygen.
Table 1. Results of Double Label Experiment on 2
label
reactant 1a
intra.b
inter.c
4d
12C,16
13C,16
12C,18
13C,18
O
50 ( 3
5 ( 2
0
50 ( 3
5 ( 2
0
27 ( 2
27 ( 3
22 ( 3
22 ( 3
50 ( 3
5 ( 2
0
Alkenes are among the least reactive species that are
oxidized by N-sulfonyl oxaziridines and are therefore
expected to be more sensitive to perturbations from the ideal
transition-state geometries than less selective, more reactive
nucleophilic species. Compounds 2 and 3 were prepared and
their reactivities examined. Analyses of molecular models
suggest that 2 is capable of intramolecularly transferring
oxygen from the oxaziridine to the alkene through a transition
state analogous to 1b. Oxaziridine 3 cannot intramolecularly
achieve a transition-state geometry similar to 1b, but could
intramolecularly rearrange through a transition state analo-
gous to 1a. If the transition state for oxygen transfer to give
an epoxide cannot be achieved, the reaction may take place
intermolecularly. Observation of an intermolecular reaction
at high dilution is taken as evidence that a system cannot
achieve the proper orientation of atoms in transition state
intramolecularly due to the tether linking the reactive
functionalities.
O
O
O
45 ( 5
45 ( 5
44 ( 3
a All isotope ratios were measured by FI/MS. b Calculated intramolecular
result based on the isotopic enrichment of the starting materials. c Calculated
Intermolecular result assumes complete scrambling of the isotopic labels
and negligible heavy atom isotope effects. d Experimentally determined
isotope ratio for a derivative of product 4. Refer to the supplementary
information for details.
2 as a function of time. The reaction was first order at a
concentration of 0.03 M with a rate constant of (1.6 ( 0.3)
× 10-4 (s-1), corresponding to a half-life of 72 min at 25
°C.
The fact that 2 intramolecularly isomerizes implies that
reaction via a transition state analogous to 1b is a viable
pathway for this compound. To demonstrate that the reaction
Oxaziridine 2 isomerized to 4 in 0.05 M chloroform
solutions. The molecularity of this transformation was
established by a double-labeling experiment. Doubly labeled
1-13C,18O was prepared and a ∼1:1 mixture of 1 and
1-13C,18O was allowed to react at a concentration of 0.05 M
in CDCl3 at 60 °C. The results of that experiment are
summarized in Table 1. These data demonstrate that 2
undergoes oxygen transfer intramolecularly.
of 2 is not atypical of N-sulfonyl oxaziridine oxidations, a
linear free-energy study was carried out. The rates of
isomerization of 5, 6, and 7 were measured. In each case
first-order kinetics were observed. The rate constants and
relative rates are given in Table 2. The presence of a p-NO2
Table 2. First-Order Rate Constants for the Isomerization of 2
reactant
kobs (s-1
)
relative rate
2
5
6
7
(1.6 ( 0.3) × 10-4
(1.25 ( 0.05) × 10-4
(2.5 ( 0.3) × 10-4
(9 ( 2) × 10-4
1.00
0.93
1.84
6.75
group accelerates the rate of reaction while the electron-
donating p-CH3 group retards the rate of reaction. A plot of
these data against σp gave a line with a slope (F) of 0.95 (
0.2. (r ) 0.990).
Davis and co-workers reported F ) 1.07 ( 0.15 (r )
0.981)2b for the reaction of 8-11 with 1-methylcyclohexene.
Within the error of the measurements, the F values cor-
respond, and we conclude that the intramolecular rearrange-
ment of 1 takes place through a transition state which is
electronically similar to the intermolecular reaction of 8-11.
If transition state 1b were operative only for 2, and 5-7
and 1a were operative for 8-11, different values for F would
The rate of isomerization of 2 was measured by 1H NMR
integration of the oxaziridine, alkene, and methyl groups of
(4) Evans, D. A.; Morrissey, M. M.; Dorow, R. L. J. Am. Chem. Soc.
1985, 107, 4346.
(5) Mithani, S.; Drew, D. M.; Rydberg, E. H.; Taylor, N. J.; Mooibroek,
S.; Dmitrienko, G. I. J. Am. Chem. Soc. 1997, 119, 1159.
(6) Beak, P. Acc. Chem. Res. 1992, 25, 215.
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Org. Lett., Vol. 1, No. 9, 1999

be expected. The former would be expected to be more
sensitive to electronic substitution on the aromatic ring as
there is more negative charge is on the nitrogen in 1b than
1a.
oxygen intramolecularly. Epoxide 13 is formed by an
intermolecular reaction. These experiments also demonstrate
that the oxaziridine of 3 is of similar reactivity to the
oxaziridine of 12. We therefore conclude that reaction of 3
through a transition state analogous to 1a is disfavored.7
These results do not exclude the possibility that reaction
pathways through transition states similar to 1a could also
be viable. To assess this transition-state geometry, oxaziridine
3 was investigated. At higher concentrations (0.1 M in
CDCl3), 3 was found to produce a small amount of 13 after
several days at 56 °C. Hydrolysis of the sulfonimine
apparently follows oxygen transfer. In addition, a large
number of unidentified decomposition products were formed.
At lower concentrations (0.005 M in CDCl3), 3 completely
decomposed over 7 days at 56 °C without producing a
detectable amount of 13. These observations imply that the
reaction of 3 to ultimately produce epoxide 13 intermolecular.
In summary, we have shown that the transition-state
structures for the reaction of N-sulfonyl oxaziridines with
olefins are best represented by Figure 1b and that reaction
via transition states analogous to 1a is not favorable.8
Transition state 1b may lead to hemiaminal intermediates
that have been observed spectroscopically for the reaction
of N-sulfonyl oxaziridines with organomagnesium reagents2a
and have been suggested as intermediates in other transfor-
mations.4,5 We suggest that anionic and neutral nucleophiles
react with N-sulfonyl oxaziridines through similar transition
states. The preferred trajectory for substitution at the oxygen
atom of the oxaziridine places the entering and leaving
groups in apical positions with respect to the transferred
oxygen. This transition state is similar to that of substitution
at the oxygen atom of a peroxide and is analogous to an
SN2 displacement at oxygen.9
Attempts to execute double-label experiments were ham-
pered by our inability both to obtain isotopic distribution
data for 13 and to derivitize 13 to a more suitable compound
for analysis without loss of the oxygen label.
Acknowledgment. This work was supported by a grant
from the National Science Foundation (98-19422).
To further explore the reactivity of 3, an intermolecular
reporter 14, was employed. Equimolar amounts of 3 and 14
were sealed in an NMR tube and allowed to react in CDCl3
at 56 °C. At higher concentrations (0.1 M total concentration
of alkene), both 13 and 15 were detected in the mixture after
hydrolysis along with a number of decomposition products.
At lower concentrations (0.01 M total concentration of
alkene), a trace amount of 15 was detected after 82 h. At
very low concentrations (0.005 M total concentration of
alkene), 3 completely decomposed after 7 days at 56 °C while
producing neither 13 nor 15. Reporter 14 was found to react
with 12 to produce 15 at higher concentrations (0.05 M with
respect to each species), but not at lower concentrations
(0.005 M with respect to each species).
Supporting Information Available: Experimental pro-
cedures for the preparation of all compounds and intermedi-
ates and sample kinetic data for 1. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL990969W
(7) The observation that at 0.01 M a trace of epoxide 10 can be detected
is best understood in terms of competitive reaction pathways. As 2
decomposes, its relative concentration decreases and the velocity of the
epoxidation 9 increases relative to the epoxidation of 2 (or products derived
from 2). Alternatively, the reactivity of the alkene of 9 could be slightly
different than the reactivity of the alkene of 2 or products that result from
the reaction of 2.
(8) Our experiments do not distinguish between planar and spiro transition
states. Molecular models suggest that either transition state may be available
to 2 and 3.
(9) Woods, K. W.; Beak, P. J. Am. Chem. Soc. 1991, 113, 6281. Bach,
R. D.; Winter, J. D.; McDouall, J. J. W. J. Am. Chem. Soc. 1995, 117,
8586. Yamabe, S.; Kondou, C.; Minato, T. J. Org. Chem. 1996, 61, 616.
Singleton, D. A.; Merrigan, S. R.; Liu, J.; Houk, K. N. J. Am. Chem. Soc.
1997, 119, 3385.
The fact that intermolecular epoxidation of 14 by 12 was
only observed at higher concentrations and that 3 only
produces epoxides from either itself or from 14 at the same
concentrations support the conclusion that 3 does not transfer
Org. Lett., Vol. 1, No. 9, 1999
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