Homogeneous decatungstate-catalyzed photooxygenation of tetrasubstituted alkenes: A deuterium kinetic isotope effect study

Article abstract of DOI:10.1021/jo061238u

The decatungstate W₁₀O₃₂^4- homogeneous photocatalyzed oxygenation of tetrasubstituted alkenes has been mechanistically studied. In all cases, allylic hydroperoxides are the major products. The primary inter- and intramolec

Full text of DOI:10.1021/jo061238u

Homogeneous Decatungstate-Catalyzed Photooxygenation of
Tetrasubstituted Alkenes: A Deuterium Kinetic Isotope
Effect Study
Ioannis N. Lykakis, Georgios C. Vougioukalakis, and Michael Orfanopoulos*
Department of Chemistry, UniVersity of Crete, Iraklion, Voutes 71003, Crete, Greece
orfanop@chemistry.uoc.gr
ReceiVed June 15, 2006
4-
The decatungstate W10O32 homogeneous photocatalyzed oxygenation of tetrasubstituted alkenes has
been mechanistically studied. In all cases, allylic hydroperoxides are the major products. The primary
inter- and intramolecular as well as the remote δ-secondary deuterium kinetic isotope effects for the
photooxidation of the 2,3-dimethyl-2-butene and 1,1,1-trideuterio-7-methyl-2-(trideuteriomethyl)octa-
2,6-diene along with product analysis suggest a hydrogen abstraction in the rate-determining step. For
comparison, singlet oxygen photosensitized oxidations of the above substrates were also studied.
Introduction
state W10O324-* that decays in less than 30 ps to an extremely
reactive transient,11 with a distorted geometry12 with respect to
W10O324-, which has been designated as wO.2,11,12 The wO
reactivity provides an interesting new mechanistic tool for
studies of light-induced oxidations, since it proceeds exclusively
via free-radical pathways.10b
In general, the two well-established mechanisms of photo-
sensitized oxidations classified as Type I and Type II, according
to the initial interaction of the excited sensitizer (Sen*), are
shown in Scheme 1.16
Photocatalyzed reactions induced by polyoxometalates1,2 and
especially by the decatungstate2 anion W10O324-, in the presence
of molecular oxygen, lead to the oxygenation of virtually any
organic substrate.2-15 It is generally accepted that illumination
of W10O324- leads to the formation of a charge-transfer excited
(1) (a) A special issue of Chemical ReViews is devoted to polyoxometa-
lates: Hill, C. L. Ed. Chem. ReV. 1998, 98, 1-387. (b) Hill, C. L.; Prosser-
McCartha, C. M. Coord. Chem. ReV. 1995, 143, 407-455. (c) Hiskia, A.;
Mylonas, A.; Papaconstantinou, E. Chem. Soc. ReV. 2001, 30, 62-69. (d)
Neumann, R. Prog. Inorg. Chem. 1998, 47, 317-370.
(2) Tanielian, C. Coord. Chem. ReV. 1998, 178-180, 1165-1181.
(3) (a) Yamase, T.; Takabaysashi, N.; Kaji, M. J. Chem. Soc., Dalton
Trans. 1984, 793-799. (b) Yamase, T.; Usami, T. J. Chem. Soc., Dalton
Trans. 1988, 183-190.
(4) (a) Nomiya, K.; Sugie, Y.; Miyazaki, T.; Miwa, M. Polyhedron 1986,
5, 1267-1271. (b) Nomiya, K.; Miyazaki, T.; Maeda, K.; Miwa, M. Inorg.
Chim. Acta 1987, 127, 65-69. (c) Nomiya, K.; Maeda, K.; Miyazaki, T.;
Miwa, M. J. Chem. Soc., Dalton Trans. 1987, 961-962.
(5) Fox, M. A.; Cardona, R.; Gaillard, E. J. Am. Chem. Soc. 1987, 109,
6347-6354.
(6) Kothe, T.; Martschke, R.; Fischer, H. J. Chem. Soc., Perkin Trans 2
1998, 503-507.
(7) (a) Molinari, A.; Amadelli, R.; Andreotti, L.; Maldotti, A. J. Chem.
Soc., Dalton Trans. 1999, 1203-1204. (b) Molinari, A.; Amadelli, R.;
Carassiti, V.; Maldotti, A. Eur. J. Inorg. Chem. 2000, 91-96. (c) Maldotti,
A.; Amadelli, R.; Vitali, I.; Borgatti, L.; Molinari, A. J. Mol. Catal. A 2003,
203-204., 703-711.
(8) (a) Ermolenko, P. L.; Delaire, J. A.; Giannotti, C. J. Chem. Soc.,
Perkin Trans. 2 1997, 25-30. (b) Texier, I.; Delouis, F. J.; Delaire, J. A.;
Giannotti, C.; Plaza, P.; Martin, M. M. Chem. Phys. Lett. 1999, 311, 139-
145. (c) Texier, I.; Delaire, J. A.; Giannotti, C. Phys. Chem. Chem. Phys.
2000, 2, 1205-1212.
(9) (a) Duncan, D. C.; Netzel, T. L.; Hill, C. L. Inorg. Chem. 1995, 39,
4640-4646.
(10) (a) Tanielian, C.; Seghrouchni, R.; Schweitzer, C. J. Phys. Chem.
A 2003, 107, 1102-1111. (b) Tanielian, C.; Schweitzer, C.; Seghrouchni,
R.; Esch, M.; Mechin, R. Photochem. Photobiol. Sci. 2003, 2, 297-305.
(11) Tanielian, C.; Duffy, K.; Jones, A. J. Phys. Chem. B 1997, 101,
4276-4282.
(12) Duncan, D. C.; Fox, M. A. J. Phys. Chem. A 1998, 102, 4559-
4567.
(13) (a) Jaynes, B. S.; Hill, C. L. J. Am. Chem. Soc. 1995, 117, 4704-
4705. (b) Jaynes, B. S.; Hill, C. L. J. Am. Chem. Soc. 1993, 115, 12212-
12213. (c) Combs-Walker, L. A.; Hill, C. L. J. Am. Chem. Soc. 1992, 114,
938-946. (d) Renneke, R. F.; Pasquali, M.; Hill, C. L. J. Am. Chem. Soc.
1990, 112, 6585-6594. (e) Prosser-McCartha, M. C.; Hill, C. L. J. Am.
Chem. Soc. 1990, 112, 3671-3673. (f) Chambers, R. C.; Hill, C. L. Inorg.
Chem. 1989, 28, 2509-2511. (g) Renneke, R. F.; Hill, C. L. J. Am. Chem.
Soc. 1986, 108, 3528-3529.
(14) (a) Lykakis, I. N.; Tanielian, C.; Orfanopoulos, M. Org. Lett. 2003,
5, 2875-2878. (b) Lykakis, I. N.; Orfanopoulos, M. Tetrahedron Lett. 2004,
45, 7645-7649.
(15) Awad, K. M.; Anderson, B. A. J. Am. Chem. Soc. 1990, 112, 1603-
1606.
10.1021/jo061238u CCC: $33.50 © 2006 American Chemical Society
Published on Web 10/11/2006
8740
J. Org. Chem. 2006, 71, 8740-8747

Decatungstate-Catalyzed Photooxygenation of Tetrasubstituted Alkenes
SCHEME 1. Type I and Type II Mechanisms in
Photosensitized Oxygenations
CHART 1. Tetrasubstituted Alkenes Used for the
Decatungstate-Photocatalyzed Oxygenations
SCHEME 2. Intermolecular KIEs in the Decatungstate
Photooxygenation of TMEs
In Type I reactions, the excited sensitizer reacts directly with
the substrate XH or the solvent to give electron transfer (ET)17
or hydrogen atom transfer (HAT),18 producing radicals. These
radicals then react with molecular oxygen to give oxygenated
products. In the alternative Type II mechanism, the excited
sensitizer interacts directly with molecular oxygen by energy
transfer to produce singlet molecular oxygen (1O2,1∆g).19
Subsequently, this reactive species adds to a variety of substrates
4-
giving oxygenated products. In the case of W10O32 as the
photocatalyst, hydrogen atom transfer (HAT)2,7-14 and electron
transfer (ET)10a pathways can compete in the overall process,
both leading to the formation of peroxides. Thus, in the oxidation
of organic substrates, such as alkanes,7a,8a,13 alkylarenes,14b
alcohols,4,6 arylalkanols,14a and cycloalkenes,7b a HAT mech-
anism has been reported. However, in the decatungstate-
catalyzed photooxygenation of alkenes,10a both ET and HAT
mechanisms have been proposed, with the ET being the
predominant with long irradiation times and high alkene
concentrations.
Results and Discussion
Following our general interest in the photosensitized oxy-
genation of alkenes in the presence of molecular oxygen,20 we
present here a detailed mechanistic study on the decatungstate-
photocatalyzed oxygenation of symmetrically tetrasubstituted
alkenes in the presence of O2. This was accomplished by
determining the intra- and intermolecular kinetic isotope effects
(KIEs) of the title reaction. Since KIEs have not been previously
measured, their values may shed more light on the factors
controlling the formation of the alkene-oxygenated products.
For this purpose, we have investigated the W10O324--catalyzed
photooxygenation of a series of perprotium and deuterium-
labeled tetrasubstituted alkenes such as: 1-d0, 1-d12, gem-1-d6,
2-d0, 2-d6, and 2-d3, shown in Chart 1. It is noteworthy that the
symmetrically tetrasubstituted 2,3-dimethylbut-2-enes (TMEs)
1-d0, 1-d6, and 1-d12 have been previously used as efficient
probes to determine the mechanism of several enophiles, such
as singlet oxygen (1O2),20 triazolinediones (TADs),21 and
nitrosoarenes (ArNO).22
The homogeneous decatungstate-photocatalyzed oxygenations
of the symmetrically substituted, deuterium-labeled alkenes were
carried out as follows: A solution of the alkene (5.0 × 10-3
M) and W10O324- (5 × 10-5 M), in oxygen-bubbled acetonitrile,
was irradiated with a Variac Eimac 300 W Xenon lamp (λ >
300 nm) as the light source. To avoid deactivation of the
photocatalyst, due to the formation of a long-lived complex
between the catalyst and alkenes at higher alkene concentrations
(1 × 10-1 M),10a lower alkene concentrations (5.0 × 10-3 M)
were used in this work. The product distribution was measured
by integration of the appropriate peaks in the 1H NMR spectra,
as well as by GC analysis of the allylic alcohols produced from
the reduction of the initially formed allylic hydroperoxides by
triphenylphosphine. The intermolecular KIEs were obtained by
the competitive oxidation of equimolar mixtures of the TMEs
1-d0 vs 1-d12 and 2-methyl-1,1-diphenylpropene 2-d0 vs 2-d6
in separate experiments (Scheme 2). For better accuracy, intra-
and intermolecular KIEs were obtained by keeping the conver-
sion of each competition reaction lower than 40%.
(16) (R) Schenck, G. O.; Koch, E. Z. Electrochem. 1960, 64, 170-177.
(b) Gollnick, K. AdV. Photochem. 1968, 6, 1-122. (c) Foote, C. S. Science
1968, 162, 963-970. For a recent article, see: Tanielian, C.; Mechin, R.;
Seghrouchni, R.; Schweitzer, C. Photochem. Photobiol. 2000, 71, 12-19.
(17) (a) Foote, C. S. Tetrahedron 1985, 41, 2221-2227. (b) Eriksen, J.;
Foote, C. S. J. Am. Chem. Soc. 1980, 102, 6083-6088.
(18) Baciocchi, E.; Bietti, M.; Lanzalunga, O. Acc. Chem. Res. 2000,
33, 243-251.
(19) (a) Wasserman, H. H.; Murray, R. W. Singlet Oxygen; Academic
Press: New York, 1979. (b) Frimmer, A. A.; Stephenson, L. M. Singlet
Oxygen. Reactions, Modes and Products; Frimer, A. A., Ed.; CRC Press:
Boca Raton, FL, 1985. (c) Foote, C. S.; Clennan, E. L. ActiVe Oxygen in
Chemistry; Foote, C. S., Valentine, J. S., Greenberg, A., Liebman, J. F.,
Eds.; Chapman & Hall: London, 1995; pp 105-140.
(21) (a) Vougioukalakis, G. C.; Orfanopoulos, M. Synlett 2005, 713-
731. (b) Orfanopoulos, M.; Smonou, I.; Foote, C. S. J. Am. Chem. Soc.
1990, 112, 3607-3610. (c) Cheng, C. C.; Seymour, C. A.; Petti, M. A.;
Greene, F. D. J. Org. Chem. 1984, 49, 2910-2916.
(22) Adam, W.; Krebs, O.; Orfanopoulos, M.; Stratakis, M.; Vou-
gioukalakis, G. C. J. Org. Chem. 2003, 68, 2420-2425.
(20) For reviews, see (a) Stratakis, M.; Orfanopoulos, M. Tetrahedron
2000, 56, 1565-1615. (b) Stephenson, L. M.; Grdina, M. B.; Orfanopoulos,
M. Acc. Chem. Res. 1980, 13, 419-425.
J. Org. Chem, Vol. 71, No. 23, 2006 8741

Lykakis et al.
SCHEME 3. Intramolecular Kinetic Isotope Effects in the
SCHEME 4. Proposed Transition States in the
Decatungstate Photooxygenation of gem-1-d6 and 2-d3
Decatungstate Allylic Hydrogen Abstraction and in the
Cycloaddition of TCNE to 2,4-Hexadiene
Irradiation of 1-d0 vs 1-d12 at 5-10 °C gave the corresponding
tertiary hydroperoxides 1a and 1c as the major products, in about
92% relative yield. The hydroperoxide ratio of (1a + 1b)/(1c
+ 1d), determined by 1H NMR, is proportional to the observed
intermolecular isotope effect and was found to be (kH/kD)obs
)
1.82 ( 0.03. The isotopic ratio may also be determined from
the integration of the well-separated (capillary column) GC
signals of the allylic alcohols protio vs deuterium after reduction
of the initially formed allylic hydroperoxides by triphenylphos-
phine, as well as from the remaining alkenes23 1-d0 and 1-d12
(see the Supporting Information). It is interesting to mention
that the capillary column (60 m, 5% phenyl methylpolysiloxane)
was capable of separating with baseline resolution of the protio
allylic alcohol and starting alkene from their corresponding
deuterium-labeled analogues.
The photooxidation of the mixture 2-d0 vs 2-d6, according to
the above procedure, gave apart from the primary hydroperox-
ides 2a and 2c substantial amounts of the aldehydes 2b and 2c,
as well as small amounts of benzophenone and epoxides (less
than 10% relative yield). The photooxygenation results with
decatungstate as a photocatalyst are shown in Scheme 2.
Again in this case, a substantial primary intermolecular
isotope effect was measured and found to be (kH/kD)obs ) 1.74
( 0.03. This isotope effect was determined from the ratio of
protio vs deuterium hydroperoxides and aldehydes (2a + 2b)/
(2c + 2d), as well as from the ratio of the remaining alkenes
2-d0 vs 2-d6, by the use of gas chromatography. Aldehydes 2b
and 2d were formed due to further oxidation and/or decomposi-
tion24 of the initially formed primary hydroperoxides 2a and
2c, respectively. When the photooxygenation of 2-d0 vs 2-d6
was run in the presence of 2 equiv of Et3SiH, the corresponding
relative yield of the primary hydroperoxides 2a and 2c increased
from 55% to 90%. In this case, the ratio of protio and deuterium
hydroperoxides and aldehydes (2a + 2b)/(2c + 2d), which is
proportional to the intermolecular KIE, was found to be (kH/
kD)obs ) 1.79, similar (within experimental error) to the one
found in the absence of Et3SiH. The increase of the primary
hydroperoxides was attributed previously14b to the fact that the
corresponding peroxy radical intermediates are trapped by Et3-
SCHEME 5. Synthesis of 1,1,1-Trideuterio-7-methyl-2-
(trideuteriomethyl)octa-2,6-diene (3-d6)
SiH.25 Also, the primary KIEs were measured in three different
conversions, all of them lower than 40%, and was found to be
in the range of 1.74-1.79. These results suggest that the
aldehyde formation, which is the result of partial hydroperoxide
decomposition, has a negligible influence in the overall primary
intermolecular KIE of this oxidation.
The primary isotope effects suggest that a C- H(D) bond
cleavage occurs in the rate-determining step of the oxygen-
ation.26,27 The relatively modest, for organic reactions, value
of the primary isotope effects, measured in these reactions [(kH/
kD)obs ) 1.74-1.82], may be attributed either to a bent transition
state (i.e., nonlinear hydrogen atom transfer)28 and/or to an early
transition state,29 in which C-H(D) bond cleavage is not
extensively developed.
It was previously reported that the dicyanoanthracene (DCA)-
sensitized photooxygenation of phenyl-substituted alkenes leads
(25) For Et3SiH as a hydrogen donor, see: (a) Chatgilialoglu, C. Chem.
ReV. 1995, 95, 1229-1251.. (b) Chatgilialoglu, C.; Newcomb, M. AdV.
Organomet. Chem. 1999, 44, 67-112. (c) Lucarini, M.; Marchesi, E.;
Pedulli, F. G.; Chatgilialoglu, C. J. Org. Chem. 1998, 63, 1687-1693.and
ref 14b.
(26) For theory and examples of KIEs, see: (a) Melander, L.; Saunders,
W. H. Reaction Rates of Isotopic Molecules; Wiley-Interscience: New York,
1980. (b) Carpenter, K. B. Determination of Organic Reaction Mechanisms.
Isotope Effects: John Wiley & Sons: New York, 1984; Chapter 5.
(27) Matsson, O.; Westaway, K. C. AdV. Phys. Org. Chem. 1996, 31,
143-248.
(28) (a) More, O’Ferrall, R. A. J. Chem. Soc. 1970, 13, 785-790. (b)
Karabatsos, G. J.; Tornaritis, M. Tetrahedron Lett. 1989, 30, 5733-5736.
(29) Hammond, G. S. J. Am. Chem. Soc. 1955, 77, 334-338.
(23) For the equation used to calculate the isotope effect, see: Stratakis,
M.; Orfanopoulos, M.; Foote, C. S. J. Org. Chem. 1998, 63, 1315-1318.
(24) Russell, G. A. J. Am. Chem. Soc. 1957, 79, 3871-3877.
8742 J. Org. Chem., Vol. 71, No. 23, 2006

Decatungstate-Catalyzed Photooxygenation of Tetrasubstituted Alkenes
SCHEME 6. Intramolecular Kinetic Isotope Effects in the Decatungstate Photooxygenation of 3-d6
mainly to benzophenone and the corresponding epoxide of the
alkene by an electron-transfer mechanism.17 Benzophenone was
the cleavage product from the decomposition of the correspond-
ing 3,3-dimethyl-4,4-diphenyl-1,2-dioxetane. In this work, the
formation of small amounts of benzophenone and epoxide
products through the decatungstate photocatalyzed oxygenation
of 2-d0 indicates that the electron-transfer mechanism possesses
a minor contribution to the overall oxidative process.
kD)pr, a R-secondary [(kH/kD)R]2, a γ-secondary [(kH/kD)γ]3, and
a δ-secondary isotope effect [(kH/kD)δ]6 and [(kH/kD)δ]-6 re-
spectively (Scheme 4), according to eqs 1 and 2.26
(kH/kD)obs
)
[(kH/kD)pr]‚[(kH/kD)R]2‚[(kH/kD)γ]3‚[(kH/kD)δ]6 ) 1.83 (1)
(kH/kD)′obs
)
To assess further the extent of bond making and bond
breaking in the transition state, we measured the intramolecular
isotope effects of the sensitized photooxygenations of the two
alkenes, gem-1-d6 and 2-d3, in separate experiments, under the
experimental conditions described above (Scheme 3). In the case
of gem-1-d6, the product ratio (1e + 1f)/(1g + 1h), is
[(kH/kD)pr]‚[(kH/kD)R]2‚[(kH/kD)γ]3‚[(kH/kD)δ]-6 ) 1.56 (2)
Although the primary, the R-secondary, and the γ-secondary
isotope effects in both cases (1-d0 vs 1-d12 and gem-1-d6) have
contributions that are in the same direction (i.e., they all favor
hydrogen abstraction), the δ-secondary isotope effect favors
hydrogen abstraction in 1-d0 vs 1-d12 but deuterium abstraction
in gem-1-d6 (inverse contribution). We therefore propose that
the small difference in the observed, overall isotope effects in
the competitions 1-d0 vs 1-d12 [(kH/kD)obs ) 1.82] and gem-1-
d6 [(kH/kD)′obs ) 1.56)] may be attributed to the opposite
contributions of the δ-secondary isotope effects. Assuming that
(kH/kD)pr, (kH/kD)R, and (kH/kD)γ are the same for 1-d0 vs 1-d12
(intermolecular) and gem-1-d6 (intramolecular) competitions, the
ratio of eq 1/eq 2 gives [(kH/kD)δ]12 ) 1.82/1.56 ) 1.17, which
corresponds to a (kH/kD)δ ≈ 1.02 per deuterium atom. This value
is reasonable for a remote secondary isotope effect31a and
comparable to a normal remote ꢀ-secondary isotope effect, found
previously in the dipolar cycloaddition of TCNE to 2,4-
hexadiene (TS4, Scheme 4).31b
1
proportional to the isotopic ratio (kH/kD)′obs. H NMR integra-
tions of the 1e vinyl protons at 4.98-5.02 ppm and the 1f
methylene protons at 4.05 ppm, as well as the integrals at 1.39
and 1.85 ppm of the two methyl groups of 1g and 1h,
correspondingly, determine the intramolecular primary isotope
effect ratio, which is equal to (kH/kD)′obs ) 1.56 ( 0.05.
Similarly, the proper proton integrations determine the product
ratio (2e + 2f)/(2g + 2h), which is proportional to the
intramolecular primary isotope effect (kH/kD)′obs. This isotopic
ratio was found to be (kH/kD)′obs ) 2.03 ( 0.08.
These results, primary intramolecular (kH/kD)′obs ) 1.56-2.03
and primary intermolecular isotope effect, (kH/kD)obs ) 1.74-
1.82, suggest an extensive C-H(D) bond cleavage in the rate-
determining step,26,27 leading to a radical intermediate.7b This
radical intermediate is then trapped by molecular oxygen to form
mainly allylic hydroperoxides and further oxidation products
such as aldehydes. This conclusion, derived from the present
isotope effect studies of tetrasubstituted alkenes, is in agreement
with previous studies of decatungstate-sensitized oxygenation
of cycloalkenes.3b,7b,30
To test this mechanism and directly obtain the remote isotope
effect contribution to the reaction rate, we designed substrate
3-d6 (1,1,1-trideuterio-7-methyl-2-(trideuteriomethyl)octa-2,6-
diene). In this substrate, unlike TME-d6 (gem-1-d6), the geminal
methyls are placed apart from the deuterium methyl groups.
This compound was prepared according to the procedure shown
in Scheme 5.
A further analysis of the observed isotope effects provides
an estimate of the remote KIEs, which contribute to the overall
reaction rates. For example, in both inter- and intramolecular
competitions of 1-d0 vs 1-d12 and gem-1-d6 (Scheme 4), the
observed isotope effects can be factored into a primary (kH/
The photocatalyzed oxidation of 3-d6 was carried out under
the above-described reaction conditions. In order to avoid the
(31) (a) Shiner, V. J.; Kritz, G. S., Jr. J. Am. Chem. Soc. 1964, 86, 2643-
2645. (b) Vassilikogiannakis, G.; Orfanopoulos, M. Tetrahedron Lett. 1996,
37, 3075-3078.
(30) Lykakis, I. N.; Orfanopoulos, M. Synlett 2004, 2131-2134.
J. Org. Chem, Vol. 71, No. 23, 2006 8743

Lykakis et al.
SCHEME 8. Transition State of the Decatungstate-
SCHEME 7. δ-Secondary Kinetic Isotope Effect in the
Decatungstate Photooxidation of 3-d6
Photosensitized Oxygenation of the Alkenes 1 and 2
formation of the dihydroperoxides observed in previous studies
of similar substrates with singlet oxygen as the enophile,32 the
reactions were kept at low conversions (<10%). The product
distribution was measured by integrating the appropriate peaks
in the 1H NMR spectra. These results are summarized in Scheme
6.
follows: In the first step of the overall reaction and under
irradiation conditions, the decatungstate anion changes into the
established relatively long-lived excited intermediate wO.2,10-12
This reactive intermediate abstracts an allylic hydrogen from
the tetrasubstituted alkene (TS7), producing the corresponding
reduced forms of H+W10O325- and/or HW10O324- and a radical
intermediate (RI3).2,3,7,13 These radicals can exist either as a
solvent cage radical pair or as a free-radical intermediate
(Scheme 8). However, the radical pair can also diffuse freely
throughthesolutiontothecorrespondingfree-radicalintermediate.13c
From both radical intermediates the one-electron-reduced species
Irradiation of 3-d6 for 30 s at 5 °C afforded the corresponding
allylic tertiary hydroperoxides 3g and 3h as the major products
(61% relative yield), along with primary, 3c-f, and secondary,
3a and 3b, hydroperoxides in 19.5% and 19.5% relative yields.
No dihydroperoxides were observed during the photocatalyzed
reaction. The ratio of the tertiary hydroperoxides 3g/3h is
directly proportional to a remote δ-secondary isotope effect,
which was calculated to be (kH/kD)δ ) 1.18 ( 0.04, (1.03 per
deuterium atom). This 3g/3h ratio was determined by 1H NMR
integration of the two methyls at 1.33 ppm for 3g and the two
methyls at 1.71 ppm for 3h (Scheme 6). This small δ-secondary
isotope effect supports the formation of radical intermediates,
RI1 and RI2, in the rate-determining step through the transition
states TS5 and TS6 (Scheme 7). This value, obtained directly
from the intramolecular isotopic competition in substrate 3-d6,
is very similar, within experimental error, to the value of
δ-secondary isotope effect calculated from eq 1 and eq 2, in
the case of substrates 1-d0 vs 1-d12 and gem-1-d6. This is also
comparable to a normal remote secondary isotope effect obtained
previously in other systems, where dipolar transition states were
proposed [(kH/kD)secondary ) 1.05-1.10 per deuterium].26,27,33
Moreover, the hydroperoxides ratio of (3a + 3c + 3e)/(3b +
3d + 3f) is proportional to the observed intramolecular isotope
effect, which was calculated to be (kH/kD)′obs ) 1.78 ( 0.07.
This KIE is the result of the combination of both the primary
and the R-secondary isotope effects.
4-
of decatungstate reoxidizes in the presence of O2 into W10O32
and the corresponding hydroperoxide.3,7,10 In a previous study,
the adsorption spectra of the decatungstate during the alkene
photooxygenation reaction showed the formation of both one-
and two-electron reduced forms of the decatungstate, with the
former as the major in low irradiation time and low substrate
concentration.10a It is noteworthy that in the present work all
the reactions were carried out in less than 15 min irradiation
time and the alkene concentrations were as low as 5.0 × 10-3
M. The continuous flow of O2 into the reaction mixture during
the irradiation enhances the reoxidation pathway, regenerating
the decatungstate anion. Under these conditions and according
to the present isotope effect results found in the decatungstate-
photocatalyzed oxygenation of tetrasubstituted alkenes, a HAT
mechanism is the predominant.
As we mentioned previously in this work, unlike the alkyl-
substituted alkenes 1-d0, 1-d6, and 1-d12, the photooxidations
The significant inter- and intramolecular primary isotope
effects in the decatungstate-catalyzed photooxygenation of
symmetrically tetrasubstituted alkenes support a hydrogen
abstraction in the rate-determining step, as shown by transition
state TS7 (Scheme 8). The mechanism of this reaction, based
on the KIEs and literature results,2,3,7,10 can be summarized as
(32) Tanielian, C. Ghaineaux, J. Photochem. Photobiol. 1978, 28, 487-
492.
(33) (a) Shiner, V. J.; Murr, B. L.; Heineman, G. J. Am. Chem. Soc.
1963, 85, 2413-2416. (b) Shiner, V. J.; Byddnbaum, W. E.; Murr, B. L.;
Lamaty, G. J. Am. Chem. Soc. 1968, 90, 418-426.
FIGURE 1. Regioselective addition of molecular oxygen due to steric
and electronic factors.
8744 J. Org. Chem., Vol. 71, No. 23, 2006

Decatungstate-Catalyzed Photooxygenation of Tetrasubstituted Alkenes
TABLE 1. Inter- and Intramolecular KIEs in Decatungstate and Singlet Oxygen Photosensitized Oxidations of Tetrasubstituted Alkenes
of diarylalkenes 2-d0, 2-d3, and 2-d6 gave mainly primary
hydroperoxides. Examination of the possible transition states
leading to the primary (when R is phenyl) and the tertiary (when
R is methyl) hydroperoxides may provide a satisfactory
explanation (Figure 1). In transition state TS8, the oxygen
approach on the terminal carbon, leading to the primary
hydroperoxide, is expected to be more favorable than the attack
on the tertiary carbon, where the nonbonding interactions
between the large phenyl groups (substantially out of the radical
plane) and the incoming oxygen are relatively stronger. In
addition, the observed regioselective addition of molecular
oxygen shown by TS8, may also be attributed to electronic
factors. The two phenyl groups next to the conjugated allyl-
radical moiety, although not coplanar to the radical plane, must
provide significant stabilization to this radical through resonance.
This effect decreases kinetically the reactivity toward molecular
oxygen,34 compared to the other terminal radical carbon, where
this resonance stabilization is absent. However, in transition state
TS9, where the previous relative steric interactions and electronic
effects are diminished,34 the major product is the tertiary
hydoperoxide. Thus, both stereo- and electronic effects lead to
the observed regioselective formation of primary hydroperoxides
for the diarylalkenes, whereas in the case of TMEs, the major
products are the tertiary allylic hydroperoxides.
allylic hydroperoxides are completely different than those of
singlet oxygen reactions with the same substrates (Table 1). This
is clearly demonstrated by the photooxygenation of substrates
1-d0 vs 1-d12. In the case of decatungstate as the catalyst, a
substantial primary intermolecular isotope effect kH/kD ) 1.82
was found in contrast to the negligible or absent kH/kD ) 1.02
when the photosensitized singlet oxygen was the reactive
species. Similarly, in the case of 2-d3, a substantial intramo-
lecular isotope effect kH/kD ) 2.03 was obtained with wO/O2
as the oxidizing system, whereas again a negligible kH/kD
)
1
1.02 was measured with O2. These isotope effect results also
confirm the otherwise previously known different mechanistic
routes of these two oxidizing systems.
Conclusion
In conclusion, the primary and the normal secondary kinetic
4-
isotope effects, as well as the product analysis of the W10O32
photocatalytic oxidations of symmetrically tetrasubstituted
deuterium-labeled alkenes, support an allylic hydrogen atom
abstraction in the limiting step. In the decatungstate-catalyzed
photooxygenation of tetrasubstituted alkenes the allylic hydro-
peroxides are formed as the only or major products. This result
is consistent with a HAT mechanism. In the case of diaryl-
substituted olefins, a part of the dominant HAT mechanism,
the small amounts of epoxides or cleavage products are
attributed to a simultaneous but less extended electron-transfer
mechanism. In the case of substrate 3-d3, the remote δ-secondary
kinetic isotope effect indicates again that hydrogen abstraction
occurs in the rate-determining step. With simple alkenes, the
decatungstate catalyst abstracts an allylic hydrogen from the
tetrasubstituted alkene in the rate-determining step, producing
For comparison purposes, we also measured the inter- and
1
intramolecular isotope effects in the singlet oxygen O2 ene
reaction with alkenes 1-d0, 1-d12, 2-d0, 2-d6, gem-1-d6, and 2-d3.
According to previous mechanistic studies,20-22 based on the
inter- and intramolecular isotope effects of TMEs reactions with
singlet oxygen,20 a stepwise mechanism with an irreversible
formation of a singlet oxygen-alkene perepoxide intermediate
has been established (Table 1). Later on, Singleton and
co-workers, based on theoretical and experimental work,
proposed a two-step no-intermediate mechanism with a rate-
limiting transition state, resembling that for the formation of a
perepoxide intermediate in the initially proposed stepwise
process.35 In the present work, the isotope effect values of the
decatungstate-photocatalyzed reaction with alkenes leading to
the corresponding reduced forms H+W10O325- and/or HW10O32
4-
together with a radical intermediate. These radicals, which can
exist as a radical pair and/or as free radical intermediates, are
4-
trapped by molecular oxygen producing the W10O32 and the
corresponding allylic hydroperoxides.
Experimental Section
(34) (a) Font-Sanchis, E.; Aliaga, C.; Bejan, E. V.; Cornejo, R.; Scaiano,
J. C. J. Org. Chem. 2003, 68, 3199-3204. (b) Maillard, B.; Ingold, K. U.;
Scaiano, J. C. J. Am. Chem. Soc. 1983, 105, 5095-5099.
(35) Singleton, D. A.; Hang, C.; Szymanski, M. J.; Meyer, M. P.; Leach,
A. G.; Kuwata, K. T.; Chen, J. S.; Greer, A.; Foote, C. S.; Houk, K. N. J.
Am. Chem. Soc. 2003, 125, 1319-1328.
General Procedure for the Decatungstate Catalytic Photo-
1
oxidations. H NMR and 13C NMR spectra were recorded on a
500 MHz spectrometer in CDCl3. The catalytic photooxidations
were monitored by using gas chromatography with a 60 m capillary
1
column (5% phenyl methylpolysiloxane) and H NMR spectros-
J. Org. Chem, Vol. 71, No. 23, 2006 8745

Lykakis et al.
copy. Catalytic photooxidations were achieved with a Xenon Variac
Cermax 300 W lamp. Flash chromatography was carried out on
SiO2 (silica gel 60, SDS, 230-400 mesh ASTM). Drying of organic
extracts during workup of reactions was performed over anhydrous
MgSO4. Evaporation of solvents was accomplished with a rotary
evaporator. The solvent used was HPLC-grade acetonitrile, sample
size was 4 mL, and the concentrations of [Bu4N]4W10O32 and
alkenes were 5 × 10-4 and 5 × 10-3 M, respectively. The
photooxidations were carried out in a quartz cell. Samples were
irradiated for 30 s to 15 min with oxygen bubbling. During
irradiation, the reaction mixtures were cooled with ice water and
monitored by gas chromatography. Acetonitrile was removed under
reduced pressure. Tetrabutylammonium decatungstate was synthe-
sized and purified by literature procedures.36 The 1H and 13C NMR
spectroscopic data for 1-d0, 1-d6, 1-d12, 2-d0, 2-d3, 2-d6, and 3-d6
are given below:
1,1,1,4,4,4-Hexadeuterio-2,3-bis(trideuteriomethyl)-2,3-bu-
tanediol (Pinacol-d12). Pinacol hydrate was prepared according to
the literature procedure.37b A flame-dried, 100 mL, round-bottomed
flask, equipped with a magnetic stirrer, reflux condenser, and an
addition funnel, was charged with 1.6 g (65.8 mmol) of magnesium
turnings and 16 mL of dry benzene. A solution of mercuric chloride
(1.8 g) in acetone-d6 (10 mL, 138 mmol) was added gradually
through the addition funnel. When the first vigorous reaction was
over, a mixture of 5.2 mL of acetone-d6 and 4 mL of dry benzene
was added, and the flask was heated on a water bath until no further
reaction was evident (about 3 h). Through the addition funnel was
then added 4 mL of H2O, and the reaction mixture was heated for
another 1 h, cooled to about 50 °C, and filtered. The solid was
returned to the flask and heated with fresh benzene (10 mL) to
dissolve any remaining pinacol. The combined filtrates were then
condensed to one-half in order to remove the acetone; the remaining
benzene solution was treated with 6 mL of H2O and cooled to 10-
15 °C. Pinacol hydrate was precipitated, filtered, and washed with
benzene to afford 6.5 g (43% yield based on the magnesium used).
The pinacol hydrate was then dehydrated and distilled to yield 2.5
g anhydrous pinacol. MS m/z ) 130 (100, m/z ) 65).
1,1,1,4,4,4-Hexadeuterio-2,3-bis(trideuteriomethyl)but-2-
ene (1-d12). A Schlenk flask which was connected to a rotaflo trap,
cooled to -78 °C, was charged with 2.2 g (16.95 mmol) of the
diol and 2.52 g of ethyl orthoformate. The flask was heated from
125 to 140 °C over 8 h, and 1.9 mL ethanol was distilled. The
remaining colorless liquid (2-ethoxy-4,4,5,5-tetramethyl-1,3-diox-
olane-d12) was heated at 150-160 °C for 10 h, during which time
CO2 was evolved and 2.2 mL of distillate was collected. This
distillate, which was mainly TME-d12 and ethanol, was further
purified by preparative GC to afford 800 mg (6.15 mmol) 1-d12.
13C NMR (125 MHz, CDCl3): δ 123.4, 19.4 (septet, JCD ) 19
Hz). MS m/z ) 96 (100, m/z ) 46).
2,3-Dimethylbyt-2-ene (1-d0). This compound is commercially
available.1Η NMR (500 MHz, CDCl3): δ 1.66 (s, 12 H). 13C NMR
(125 MHz, CDCl3): δ 123.4, 20.3.
3-Hydroxy-2,2-dimethyl-3-(trideuterio)methyl-3-hydroxybu-
tyric Acid-4,4,4-d3. This â-hydroxy acid was prepared according
to the procedure reported in the literature.37 A flame-dried, 500
mL, three-necked round-bottomed flask, equipped with a magnetic
stirrer, reflux condenser, and an additional funnel, was charged with
14 mL (100 mmol) of dry diisopropylamine in dry THF (100 mL)
under N2. Cooling of the solution to -78 °C was followed by
dropwise addition of 100 mmol of n-BuLi, (62.5 mL 1.6 M in
n-hexane). Following the completion of the addition, the mixture
was left for 1 h at room temperature and then cooled to -78 °C
again. Next, 4.41 g (50 mmol) of isobutyric acid (1 M solution in
dry THF) was added dropwise. After the completion of the addition,
the mixture was left for 1 h at room temperature and then cooled
to 0 °C. Then, 3.7 mL (50 mmol) of acetone-d6 was added as a 2.5
M solution in dry THF. After being stire at room temperature for
12 h, the reaction mixture was poured on ice and transferred to a
separatory funnel. Following several extractions with Et2O, the
aqueous layer was acidified with 6 N HCl, and the aqueous mixture
was extracted with Et2O (5 × 50 mL). The combined extracts were
dried and evaporated to afford 6.5 g of â-hydroxy acid (85% yield),
1,1-Diphenyl-2-methylpropene (2-d0). This compound was
prepared according to the procedure described below:
1,1-Diphenyl-2-methyl-1-propanol. This compound was pre-
pared by Grignard reaction of 3.6 g (20.0 mmol) of benzophenone,
0.85 g (35 mmol) of Mg, and 4 g (24 mmol) of isopropyl iodide,
in dry ether, under argon atmosphere, at 0 °C. A total of 3.8 g of
the tertiary alcohol (85% yield) was isolated. 1Η NMR (500 MHz,
CDCl3): δ 7.65 (d, 2H, J ) 7.4 Hz), 7.59 (d, 2H, J ) 7.3 Hz),
7.39 (t, 2H, J ) 7.3 Hz), 2.85 (m, 1H), 0.92 (d, 6H, J ) 6.7 Hz).
1,1-Diphenyl-2-methylpropene (2-d0). The tertiary alcohol 1,1-
diphenyl-2-methyl-1-propanol-d0 (3.8 g) was heated at 120 °C, and
after 1 h, 2.8 g of the tetrasubstituted alkene 1-d0 (79% yield) was
isolated. 1Η NMR (500 MHz, CDCl3): δ 7.30 (t, 4H, J ) 7.4 Hz),
7.21 (t, 2H, J ) 7.3 Hz), 7.17 (d, 4H, J ) 7.3 Hz), 1.83 (s, 6H).
13C NMR (125 MHz, CDCl3): δ 143.3, 138.8, 130.9, 129.7, 127.8,
125.9, 22.4. MS m/z ) 208 (100, m/z ) 208).
1
which was used in the next step without further purification. Η
NMR (500 MHz, CDCl3): δ 6.01 (brs, 2H, -COOH + -OH),
1.26 (s, 6H).
3,3-Di(trideuterio)methyl-4,4-dimethyl-â-lactone. A one-
necked, 500 mL, round-bottomed flask equipped with a magnetic
stirrer was charged with 1.52 g (10 mmol) of the above â-hydroxy
acid in 60 mL of dry pyridine. To this solution, after cooling to
0-5 °C, was added 3.8 g (20 mmol) of p-toluenesulfonyl chloride.
After the reaction mixture was stirred for 10 min, the flask was
tapped and left in the freezer for 12 h. The reaction mixture was
then poured on crushed ice (four to five times larger in volume)
and extracted with Et2O (5 × 50 mL). The combined organic layers
were washed with aq satd NaHCO3 and H2O, dried, and evaporated
to afford 0.7 g (52% yield) of the â-lactone. 1Η NMR (500 MHz,
CDCl3): δ 1.30 (s, 6H).
1,1,1-(Trideuterio)methyl-3-methyl-2-(trideuteriomethyl)but-
2-ene (gem-1-d6). A Schlenk flask which was connected to a rotaflo
trap, cooled at -78 °C, was charged with 0.5 g (3.72 mmol) of the
above â-lactone. The flask was heated at 160 °C with concomitant
decomposition of the â-lactone to the deuterated alkene and CO2.
With the help of a slow N2 stream, 0.26 g of the alkene (77% yield)
was collected in the trap. 1Η NMR (500 MHz, CDCl3): δ 1.66 (s,
6H). 13C NMR (125 MHz, CDCl3): δ 123.4, 123.2, 20.3, 19.4
(septet, JCD ) 19 Hz).
1,1-Diphenyl-(3,3,3-trideuterio-2-(trideuteriomethyl)pro-
pene (2-d6). This compound was prepared according to the
procedure described below:
1,1-Diphenyl-(3,3,3-trideuterio-2-(trideuteriomethyl)-2-pro-
panol. This compound was prepared by the Grignard reaction of
0.7 g (3.0 mmol) of diphenylacetic methyl ester, 0.29 g (12 mmol)
of Mg, and 0.56 mL (9 mmol) of CD3I in dry ether, under argon
atmosphere, at 0 °C. The tertiary alcohol was isolated after 4 h
and directly heated in the presence of a catalytic amount of
p-toluenesulfonic acid, producing the corresponding deuterium-
labeled alkene 2-d6 (0.3 g, 79% yield). 1Η NMR (500 MHz,
CDCl3): δ 7.30 (t, 4H, J ) 7.4 Hz), 7.21 (t, 2H, J ) 7.3 Hz), 7.17
(d, 4H, J ) 7.3 Hz). 13C NMR (125 MHz, CDCl3): δ 143.3, 138.8,
130.9, 129.7, 127.8, 125.9, 21.7 (septet, JCD ) 19 Hz). MS m/z )
214 (100, m/z ) 214).
1,1-Diphenyl-3,3,3-trideuterio-2-methylpropene (2-d3). This
compound was prepared according to the procedure described
below:
3,3-Diphenyl-2-methylpropenate methyl ester. This compound
was prepared by the Wittig-Horner reaction. A solution of methyl
(36) Chemseddine, A.; Sanchez, C.; Livage, J.; Launay, J. P.; Fournier,
M. Inorg. Chem. 1984, 23, 2609-2613.
(37) (a) Crank, G.; Eastwood, F. W. Aust. J. Chem. 1964, 17, 1392-
1398. (b) Adams, R.; Adams, E. W.; Clarke, H. T.; Phillips, R. In Organic
Syntheses; John Wiley and Sons: New York, 1932; pp 448-450.
8746 J. Org. Chem., Vol. 71, No. 23, 2006

Decatungstate-Catalyzed Photooxygenation of Tetrasubstituted Alkenes
diethyl 2-phosphonopropionate (7.84 g, 35 mmol) in dry DME (25
mL) was added to a mixture of NaH (60% in parafin oil, 1.45 g,
37 mmol) in dry DME (50 mL), under an Ar atmosphere, at room
temperature. To the resulting solution, after 1 h of stirring at room
temperature, a solution of benzophenone (5.5 g, 30 mmol) in 10
mL of dry DME was added dropwise. After overnight stirring at
room temperature, the reaction was quenched with MeOH and
washed with H2O. The resulting residue, following its concentration,
was chromatographed by using a mixture of 4:1 hexane/ethyl acetate
as eluent and yielded the corresponding ester in 55% yield (4.1 g).
1Η NMR (500 MHz, CDCl3): δ 7.30 (m, 6H), 7.19 (d, 2H, J )
7.6 Hz), 7.13 (d, 2H, J ) 7.5 Hz), 3.75 (s, 3H), 2.05 (s, 3H).
3,3-Diphenyl-1,1-dideuterio-2-methylprop-2-en-1-ol. To a mix-
ture of LiAlD4 (0.5 g, 12 mmol) in dry ether 40 mL), under Ar at
0 °C, was added dropwise a solution of the previous ester (4.1 g,
17 mmol) in dry ether (10 mL). The mixture was stirred at room
temperature for 3 h. The reaction was quenched at 0 °C by adding
0.5 mL of H2O, 0.5 mL of 15% NaOH, and 1.5 mL of H2O,
followed by filtration. The mixture was washed with 5% NaHCO3
and brine, dried over MgSO4, and concentrated carefully to give
allylic alcohol-d2 (3.1 g, 80% yield).
in 5 mL of THF was added dropwise. The flask was left at room
temperature for 1 h and cooled again to 0 °C, and 5.15 mL of 1.6
M n-butyllithium solution was added dropwise. The solution was
left at room temperature for 15 min and cooled to 0 °C, and 3 mL
of acetone-d6 (40 mmol) was added. The solution was concentrated
to 10 mL, at the rotary evaporator, and 40 mL of pentanes was
added and the mixture stirred for 30 min. Filtration, evaporation
of the solvents, and purification by preparative GC gave 472 mg
1
(3.28 mmol, 40% yield) of the desired 3-d6. Η NMR (500 MHz,
CDCl3): δ 5.12 (t, 2Η), 2.73 (t, 4H), 2.02 (s, 6Η). 13C NMR (125
MHz, CDCl3): δ 131.5, 131.3, 124.5, 28.4, 28.3, 25.7, 24.8 (septet,
JCD ) 19 Hz), 17.7, 16.8 (septet, JCD ) 19 Hz). MS m/z ) 144
(100, m/z ) 69).
Decatungstate-Catalyzed Photooxygenations. The photooxy-
genations were carried out as described in general procedures. The
1H NMR spectroscopic data of the hydroperoxides and carbonyl
compounds, formed by the photooxidation of the corresponding
alkenes are the following. 2a. 1Η NMR (500 MHz, CDCl3): δ 7.90
(s, ÃOH), 7.50-7.17 (m, 10H), 4.58 (s, 2H), 1.93 (s, 3H). 2c. 1Η
NMR (500 MHz, CDCl3): δ 7.89 (s, OOH), 7.50-7.17 (m, 10H).
2b. 1Η NMR (500 MHz, CDCl3): δ 9.63 (s, CHdO), 7.84 (d, 2H,
J ) 7.3 Hz), 7.62 (t, 1H, J ) 7.3 Hz), 7.51 (t, 2H, J ) 7.3 Hz),
7.40-7.17 (m, 5H), 2.00 (s, 3H). 2d. 1Η NMR (500 MHz,
CDCl3): δ 7.84 (d, 2H, J ) 7.3 Hz), 7.62 (t, 1H, J ) 7.3 Hz), 7.51
(t, 2H, J ) 7.3 Hz), 7.40-7.17 (m, 5H). 2e. 1Η NMR (500 MHz,
CDCl3): δ 7.89 (s, ÃOH), 7.50-7.17 (m, 10H), 4.58 (s, 2H). 2g.
1Η NMR (500 MHz, CDCl3): δ 7.88 (s, OOH), 7.50-7.17 (m,
1,1-Diphenyl-3-bromo-3,3-dideuterio-2-methylpropene. To a
solution of triphenylphosphine (3.9 g, 14 mmol) in dry CH2Cl2
under Ar at 0 °C was added dropwise 0.7 mL (14 mmol) of Br2.
The PPh3Br2 complex precipitated immediately. After 1 h of stirring
at room temperature, the reaction mixture was cooled at 0 °C, and
a solution of the corresponding allylic alcohol (3.1 g, 14 mmol) in
dry CH2Cl2 was added dropwise. The solution was concentrated,
and the resulting solid residue afforded the corresponding bromide
1
10H), 1.93 (s, 3H). 2f. Η NMR (500 MHz, CDCl3): δ 9.62 (s,
CHdO), 7.84 (d, 2H, J ) 7.3 Hz), 7.62 (t, 1H, J ) 7.3 Hz), 7.51
(t, 2H, J ) 7.3 Hz), 7.40-7.17 (m, 5H). 2h. 1Η NMR (500 MHz,
CDCl3): δ 7.84 (d, 2H, J ) 7.3 Hz), 7.62 (t, 1H, J ) 7.3 Hz), 7.51
(t, 2H, J ) 7.3 Hz), 7.40-7.17 (m, 5H), 2.00 (s, 3H). 3g + 3h. 1Η
NMR (500 MHz, CDCl3): δ 7.21 (s, OOΗ, for 3h hydroperoxide),
7.20 (s, OOH, for 3g hydroperoxide), 5.68 (m, 2Η), 5.53 (d, 2H,
J) 16 Hz), 5.12 (m, 2H), 2.75 (t, 4H), 1.71 (s, 3H), 1.54 (s, 3H),
1
(2.8 g, 70% yield) after chromatographic purification. Η NMR
(500 MHz, CDCl3): δ 7.71 (d, 2H, J ) 8.0 Hz), 7.69 (d, 2H, J )
7.0 Hz), 7.58 (t, 2H, J ) 7.3 Hz), 7.49 (t, 4H, J ) 8.0 Hz), 1.98
(s, 3H).
1,1-Diphenyl-3,3,3-trideuterio-2-methylpropene (2-d3). A solu-
tion of the deuterium-labeled bromide (2.8 g, 10 mmol) in dry ether
(10 mL) was added dropwise to a mixture of LiAlD4 (0.2 g, 5 mmol)
in dry ether (30 mL) under Ar at 0 °C. The mixture was stirred at
room temperature for 3 h. The reaction was quenched at 0 °C by
the addition of 0.2 mL of H2O, 0.2 mL of 15% NaOH, and 0.6 mL
of H2O, followed by filtration. The mixture was washed with 5%
NaHCO3 and brine, dried over MgSO4, and concentrated carefully
to give alkene 2-d3 (1.6 g, 75% yield). 1Η NMR (500 MHz,
CDCl3): δ 7.30 (t, 4H, J ) 7.4 Hz), 7.21 (t, 2H, J ) 7.3 Hz), 7.17
(d, 4H, J ) 7.3 Hz), 1.83 (s, 3H). 13C NMR (125 MHz, CDCl3):
δ 143.3, 138.8, 130.9, 129.7, 127.8, 125.9, 22.4, 21.7 (septet, JCD
) 19 Hz). MS m/z ) 211 (100, m/z ) 211).
1,1,1-Trideuterio-7-methyl-2-(trideuteriomethyl)octa-2,6-di-
ene (3-d6). A flame-dried, 100 mL, round-bottomed flask, equipped
with a magnetic stirrer, was charged with 3.32 g (8.2 mmol)
methyltriphenylphosphonium iodide in 20 mL of dry THF, under
Ar. The solution was cooled to 0 °C, and 5.15 mL of 1.6 M
n-butyllithium (solution in hexanes) was added dropwise. The
orange solution was left at room temperature for 30 min and cooled
to 0 °C, and 1.1 mL (8.2 mmol) of 5-bromo-2-methyl-2-pentene
1
1.33 (s, 6H). 3a + 3b. Η NMR (500 MHz, CDCl3): δ 7.70 (s,
OOH, for 3a hydroperoxide), 7.69 (s, OOH, for 3b hydroperoxide),
5.12 (m, 2H), 5.02 (d, 2Η, J) 6 Hz), 4.32 (t, 2Η), 1.49 (m, 8H),
1
1.69 (s, 3H), 1.59 (s, 6H). 3c + 3d + 3e + 3f. Η NMR (500
MHz,CDCl3): δ 7.81 (s, OOΗ), 7.80 (s, OOΗ), 7.76 (s, OOΗ),
7.75 (s, OOΗ), 5.66 (m, 2H), 5.12 (m, 2Η), 4.51 (s, 2H (3e)), 4.38
(s, 2H (3c)), 2.03 (m, 8H), 1.74 (s, 3H), 1.70 (s, 6H).
Acknowledgment. M.O. thanks Professor R. H. Grubbs for
his generous hospitality during his sabbatical stay at Caltech
(2006). Financial support by the Greek Secreteriat of Research
and Technology (PYTHAGORAS II, 2005 and HERAKLITOS
2002) is acknowledged.
Supporting Information Available: 1H NMR and 13C NMR
spectra for labeled alkenes as well as GC chromatograms of the
oxidations. This material is available free of charge via the Internet
at http://pubs.acs.org.
JO061238U
J. Org. Chem, Vol. 71, No. 23, 2006 8747