A Reinvestigation of the Structure of the Transition State in Peracid Epoxidations. α- and β-Secondary Isotope Effects

Full text of DOI:10.1021/jo970268h

J . Org. Chem. 1997, 62, 6083-6085
6083
Ta ble 1. â-Secon d a r y Isotop e Effects of MCP BA
A Rein vestiga tion of th e Str u ctu r e of th e
Tr a n sition Sta te in P er a cid Ep oxid a tion s.
r- a n d â-Secon d a r y Isotop e Effects
Ep oxid a tion of 1-d 0 a n d 1-d 6
% convrsn
kH/kD by NMRa
kH/kD by GCb
14
20
27
1.02
0.96
0.98
0.93
0.95
Yiannis S. Angelis and Michael Orfanopoulos*
Department of Chemistry, University of Crete,
71409 Iraklion, Crete, Greece
a
b
The error was (5%. Each value is the average of three
consecutive measurements. The error was (2%. A 75 ft 50%
phenyl/50% methyl silicon a capillary column was able to separate
the protio 2-d 0 from the deutero 2-d 6.
Received February 12, 1997
The epoxidation of alkenes by peracids is a syntheti-
cally useful transformation that has been used by chem-
ists for many decades. Several mechanistic studies of
this reaction have been reported that include stereo-
chemistry,1 as well as kinetics, solvent effects,2 Hammet
correlations,3 and isotope effects.4 The most popular
mechanism was proposed5 by Bartlett in 1950 and found
support later from studies involving calculations6 and
experimental measurements.7 It involves the symmetri-
cal transfer of an oxygen atom to the alkene from the
peracid monomer. However Bartlett’s mechanism was
challenged by Hanzlik and Shearer,4 on the basis of
R-secondary isotope effects of the peracid epoxidation of
p-phenylstyrene and its deuterated analogues. They
found a substantial inverse secondary isotope effect (kH/
kD ) 0.82) for deuterium substitution at the â-carbon
(dCD2) and no isotope effect (kH/kD ≈ 1) for substitution
at the R-carbon (dCDAr). The authors concluded that
the epoxidation mechanism reported earlier by Bartlett
does not accommodate their results and suggested a
transition state which involves an open chain structure
with a large degree of charge separation as shown in TSI.
Moreover a 1,3-dipolar addition mechanism involving a
1,2-dioxolane intermediate was also proposed,8 but this
mechanism was also challenged by results based on
Hammet correlations and solvent effects.9
In order to measure the â-secondary isotope effect, we
prepared the alkenes 1-phenyl-3-methyl-2-butene, (1-d 0)
and its deuterated analog 1-phenyl-3-(methyl-d3)-2-butene-
4,4,4-d3 (1-d 6) in high purity. These substrates are well
suited to test for a charge separation in the transition
state by an isotopic intermolecular competition, because
they bear two geminal methyl groups, in 1-d 0 and its
deuterated 1-d 6 analog, next to the reactive double-bond
carbon.11
Equimolar quantities of 1-d 0 and 1-d 6 were dissolved
in chloroform-d and placed in an NMR tube. Small
quantities of m-chloroperbenzoic acid were added, at
room temperature, and after thoroughly shaking the
NMR tube, the 1H NMR spectrum of the reaction mixture
was recorded. The formation of an epoxide was the only
1
detectable product by H NMR and gas chromatography
analyses. The â-secondary isotope effect kH/kD, which is
the result of an intermolecular isotopic competition
between 1-d 0 and 1-d 6, is propotional to the ratio of 2-d 0/
2-d 6. Reactions were run in less than 30% conversion to
1
products. A typical H NMR spectrum of the reaction
mixtures20% conversionsof epoxides 2-d 0 and 2-d 6
(methyl signals at 1.42 and 1.36 ppm, benzylic hydrogens
and hydrogens next to the oxygen between 2.8 and 3.3
ppm) and unreacted alkenes 1-d 0 and 1-d 6 (methyl
signals at 1.75 and 1.73 ppm and the two benzylic
hydrogens at 3.32 ppm) is shown in Figure 1. Integra-
tions of the two methyl signals of 2-d 0 at 1.42 and 1.37
ppm as well as the hydrogens next to the oxygen and
the benzylic hydrogens of both 2-d 0 and 2-d 6 determine
the isotope effect kH/kD (2-d 0/2-d 6 ) kH/kD, Figure 1). The
â-secondary isotope effect was also determined by the
integration of gas chromatography signals of the products
2-d 0 and 2-d 6 (Figure 2). These results are summarized
in Table 1.
The controversy in the literature for the peracid
epoxidation mechanism, as well as our own mechanistic
studies on the epoxidation of alkenes with dimethyldiox-
irane,10 prompted us to reinvestigate the nature of the
transition state in the epoxidation reaction of alkenes by
m-chloroperbenzoic acid. In this paper, we report the R-
andsfor the first timesthe â-secondary isotope effects
of the peracid epoxidations and discuss the formation of
the possible transition state of this reaction, derived from
the measured isotope effects.
(1) Rebek, J ., J r.; Marshall, L.; McManis, J . Wolak. R. J . Org. Chem.
1986, 51, 1649.
(2) Dryuk V. G. Tetrahedron 1976, 32, 2855.
(3) (a) Lynch, B. M.; Pausacker, K. H. J . Chem. Soc. 1955, 1525. (b)
Ogata Y.; Sawaki, Y.; Inone, H. J . Org. Chem. 1973, 38, 1044.
(4) Hanzlik, R. P.; Shearer, G. O. J . Am. Chem. Soc. 1975, 97, 5231.
(5) Bartlett, P. D. Rec. Chem. Prog. 1950, 11, 47.
(6) Lang, T. J .; Wolber, G. J .; Bach, R. D. J . Am. Chem. Soc. 1981,
103, 3275.
The small inverse isotope effect found in the intermo-
lecular competition between 1-d 0 and 1-d 6 excludes the
formation of a dipolar transition state, TSII, similar to
that proposed earlier by Hanzlik and Shearer. In the
(7) Woods, K. W.; Beak, P. J . Am. Chem. Soc. 1991, 113, 6281.
(8) Kwart, H.; Hofman, D. M. J . Org. Chem. 1966, 31, 419.
(9) Kropf, H.; Yazdanbachsch, M. R. Tetrahedron 1974, 30, 3455.
(10) Angelis, Y.; Zhang X.; Orfanopoulos, M. Tetrahedron Lett. 1996,
37, 5991.
(11) (a) Melander, L. Saunders, W. H. Reaction rates of isotopic
molecules; Willey Interscience: New York, 1984. (b) Carperder, B. K.
Determination of organic reaction mechanism; Willey Interscience:
New York, 1984.
S0022-3263(97)00268-5 CCC: $14.00 © 1997 American Chemical Society

6084 J . Org. Chem., Vol. 62, No. 17, 1997
Notes
Sch em e 1
atom), as found recently12 in the dipolar cycloaddition of
TCNE to 2,4-dimethylhexadiene. The results are con-
sonant with a concerted mechanism as shown by TSIII
.
In the nonpolar TSIII transition state, the steric interac-
tions in going from a less crowded ground state to a more
crowded transition state would lead to a small inverse
secondary isotope effect, as found.
To assess the extent of bond making and bond breaking
in the transition state, we measured the intermolecular
R-secondary isotope effect for the reaction of MCPBA with
a 1:1 mixture of the symmetrical alkenes 2,2,7,7-tetra-
methyl-4-cis-octene (3-d 0) and its deuterated analog
(3-d 2). The preparation of 3-d 2 is summarized in
Scheme 1.
F igu r e 1. Determination of kH/kD by intergration of the proper
1H NMR signals of the products 2-d 0 and 2-d 6 (20% conver-
sion).
Similarly the product ratio of 4-d 0/4-d 2 is proportional
to the isotope effect kH/kD. Therefore the secondary
isotope effect kH/kD was determined by the 1H NMR
integration of the hydrogens next to the oxygen in 4-d 0
at 3.01 ppm and the methylenic hydrogens signals of both
4-d 0 and 4-d 2 between 1.33 and 1.54 ppm. The substan-
tial inverse R-secondary isotope effect found in this
reaction (kH/kD ) 0.81 ( 0.05) indicates a rather large
change in the hybridization of the two carbons (sp2 to
sp3) in going from the ground state to the transition state
of this epoxidation.11 This result is also consonant with
the oxygen transfer in a concerted mechanism, as shown
11
by transition state TSIII
.
Furthermore, these findings
indicate a later transition state than that of the dimeth-
yldioxirane oxidation, where a much smaller inverse
isotope effect (kH/kD ) 0.95-1.00) was found.10 This fact
is also consonant with the greater reactivity of dimeth-
yldioxirane over MCPBA, in the epoxidation of even
electron poor alkenes.
The previously reported4 unsymmetrical, open chain
transition state TSI was deduced from the unequal
inverse R-secondary isotope effects measured for the
double-bond carbons CR and Câ of arylstyrene. However,
the double-bond carbons CR and Câ are regiochemically
different with substantial differences in electron density.
Therefore, the mechanistic information derived from that
system may not be applicable to simple alkenes.
F igu r e 2. Determination of kH/kD by integration of the GC
signals of the products 2-d 6 and 2-d 0.
transition state TSII the hyperconjugative effects11 in-
volving the six hydrogen atoms in 1-d 0 versus the six
deuterium atoms in 1-d 6 are expected to give a normal
and large isotope effect (kH/kD ≈ 1.05-1.1 per deuterium
(12) Vassilikogiannakis, G.; Orfanopoulos, M. Tetrahedron Lett.
1996, 37, 3075.

Notes
J . Org. Chem., Vol. 62, No. 17, 1997 6085
of 3,3-dimethylbutyric acid in 10 mL of dry ether. After 12 h of
reflux, the reaction was worked up with base in the usual
manner (1.3 mL of water, 1.3 mL of 15% NaOH, 3.9 mL of
water). This solution was filtered, and the organic layer was
washed twice with a saturated solution of NH4Cl and once with
brine and dried over sodium carbonate. Evaporation of solvent
gave the title product in 80% yield. A similar procedure was
followed to prepare 3,3-dimethyl-1-butanol. In this case the
reduction of the acid was performed by LiAlH4 to give 2.55 g,
84% yield of the above product. 1H NMR of 3,3-dimethyl-1-
butanol-1,1-d2: 1.93 (s, 2H), 1.45 (br s, 1H, OH), 0.85 (s, 9H).
P r ep a r a tion of th e Meth a n esu lfon yl Ester of th e Above
Alcoh ol. To a solution of 2.08 g (20 mmol) of the above alcohol-
d2 and 2.6 g (30 mmol) of triethylamine in 40 mL of dry
dichloromethane cooled to -50 °C was added dropwise 2.28 (20
mmol) of methanesulfonyl chloride. After 30 min of additional
stirring the reaction mixture was treated successively with ice
cold 5% HCl aqueous solution, ice cold saturated sodium
carbonate solution, and brine. After the organic layer was dried
over magnesium sulfate, the solvent was evaporated to yield 4.1
g, 90% yield, of the above mesylate. The corresponding protio
mesylate was prepared from the protio alcohol by the same
In conclusion, our results on the epoxidation of alkenes
with m-chloroperbenzoic acid are consonant with the
oxygen transfer in a nonpolar concerted transition state
and confirm the previous spiro “butterfly” mechanism
proposed earlier by Bartlett.
1
procedure. 1H NMR: 3.08 (s, 3H), 0.69 (s, 2H), 0.97 (s, 9H). H
Exp er im en ta l Section
NMR of the protio compound: 4.22 (t, J ) 7.4, 2H), 2.98 (s, 3H),
1.67 (t, J ) 7.4, 2H), 0.90 (s, 9H).
All 1H NMR (500 MHz and 360 MHz) spectra were taken in
CDCl3, except as noted. Chemical shifts are reported in δ (ppm)
relative to internal tetramethylsilane. Analytical gas chroma-
tography was performed by using a 75 ft 50% phenyl-50%
methyl silicone capillary column and an FID detector. Reagents
were obtained from Aldrich Chemical Co.
P r ep a r a tion of 1-P h en yl-3-(m eth yl-d 3)-2-bu ten e-4,4,4-d 3,
(1-d 6). (a ) In a high-pressure bottle, a mixture of 22.0 g (120
mmol) of 2-phenylethyl bromide and 31.5 g (120 mmol) of
triphenylphosphine was stirred neat at 120 °C for a period of
16 h. After this, the phosphonium salt was obtained quantita-
tively in a glassy form, mp 90-95 °C. 1H NMR: 8.15-7.10 (m,
20H), 4.40 (m, 2H), 3.05 (m, 2H)
P r ep a r a tion of th e P h osp h on iu m Sa lts of th e Cor r e-
sp on tin g Mesyla tes. In a high-pressure bottle a mixture of
4.7 g (18 mmol) of triphenylphoshine and 3.2 g (18 mmol) of the
above mesylate was stirred neat at 120 °C over night. After
this, the phosphonium salt was obtained in gel form quantitat-
evely. 1H NMR of deuterated phosphonium salt: 7.75 (m, 15H),
2.73 (s, 3H), 1.45 (d, J ) 8.3 Hz, 2H), 0.97 (s, 9H). 1H NMR of
protio analog: 7.75 (m, 15 H), 3.25 (m, 2H), 2.73 (s, 3H), 1.45
(m, 2H), 0.93 (s, 9H).
cis-4,5-Did eu ter a ted 2,2,7,7-tetr a m eth ylocten e. In 30 mL
of dry THF was dissolved 7.1 g (16 mmol) of the phosphonium
salt prepared above. To this solution was added 8 mL of 2 M
BuLi in cyclohexane dropwise until a red color appeared. The
solution was cooled to -40 °C, and molecular oxygen was bubled
until the dissapearance of the red color. After the standard
workup procedure, 3-d 2 was isolated in crude form by distilation.
Both 3-d 2 and 3-d o were purified by gas chromatography on a
(b) Nine grams (20 mmol) of the phosphonium salt prepared
above were dissolved in 30 mL of dry tetrahydrofuran. To this
solution, 10 mL (20 mmol) of 2 M n-BuLi in cyclohexane was
added dropwise at 0 °C . After the solution was refluxed for 1
h, a deep red color appeared. To this ylide was added 1.3 g (20
mmol) of acetone-d6 (99.5 atom % D) in 20 mL of tetrahydrofuran
dropwise. After 10 h of reflux, the color still remained deep red.
The addition of 50% excess of acetone-d6 was required in order
for all the ylide to react. After the standard workup procedure,
the 1-d 6 was isolated in 65% yield. 1H NMR analysis showed
no methyl signals in 1-d 6 implying deuterium incorporation of
more than 97%. Similarly, addition of acetone instead of
deuterated acetone gave 1-d 0. Both 1-d 6 and 1-d 0 were further
purified by gas chromatography on a preparative Carbowax 20M,
1
preparative Carbowax 10% 6 ft × /4 in. column. The absence
of olefinic signals of 3-d 2 in 1H NMR indicates a deuterium
incorporation of more than 97%. 1H NMR: 1.97 (s, 4H), 0.93 (s
18H). 1H NMR of protio analogue: 5.57 (t, J ) 5.2 Hz, 2H),
1.97 (d, J ) 5.2 Hz, 4H), 0.93 (s, 18H). GC MS: m/e 170, 155,
114, 99, 83, 71, 57 (100).
Ack n ow led gm en t. We thank professor G. J . Kara-
batsos for valuable comments. One preliminary experi-
ment was performed at professor Foote’s laboratory at
UCLA, who is greatly acknowledged. The financial
support of M. S. Hourdakis and Secretariat of Research
and Technology (Grant PENED-94) are also acknowl-
edged.
1
6 ft × /4 in. column. 1H NMR of the protio olefin 1-d 0: δ 7.31-
7.15 (m, 5H), 5.36 (m, 1H), 3.32 (d, J ) 7.3 Hz, 2H), 1.72 (d, J
) 1.1 Hz, 3H), 1.70 (d, J ) 0.6 Hz, 3H). 1H NMR of the 1-d 6:
δ 7.30-7.17 (m, 5H), 5.34 (t, J ) 7.3 Hz, 1H), 3.32 (d, J ) 7.3
Hz, 2H).
P r ep a r a tion of 3-d 2 a n d 3-d 0. (a ) 3,3-Dim eth yl-1-bu -
ta n ol-1,1-d 2. To 1.25 g (30 mmol) of LiAlD4, 98% D, in 60 mL
of dry ether, cooled to 0 °C was added dropwise 3.4 g (29 mmol)
J O970268H