Oxidative single-electron transfer activation of σ-bonds in aliphatic halogenation reactions

Article abstract of DOI:10.1021/ja000193q

The reactions of a series of structurally related large-ring propellanes with iodine monochloride were studied experimentally and computationally. In the case of 1,3-dehydroadamantane (1) and [3.3.1]propellane (2) free-radical addition was observed. [3.3.2]Propellane (3) and 3,6-dehydrohomoadamantane (4), which are less prone to radical attack, selectively form products of formal double nucleophilic (oxidative) addition, e.g., dichloro (in ICl/CH₂Cl₂), dimethoxy (in ICl/CH₃OH), and diacetamino (in IC1/CH₃CN) derivatives under otherwise identical conditions. Single-electron transfer pathways involving the alkane radical cations are proposed for the activation step for aliphatic hydrocarbons with relatively low oxidation potentials such as cage alkanes. Similar mechanisms are postulated for the activation of the tertiary C - H bonds of adamantane based on H/D-kinetic isotope effect data. The latter compare well to the k(H)/k(D) value for hydrogen atom loss from the adamantane radical cation (measured 2.78 ± 0.21 and computed 2.0) and differ considerably from the kinetic isotope effects for electrophilic C - H bond activations (i.e., hydride abstraction) or for loss of a proton from a hydrocarbon radical cation (k(H)/k(D) = 1.0 - 1.4; computed 1.4). Hence, the reactions of alkanes with elementary halogens and other weak electrophiles (but strong oxidizers) do not necessarily involve three-center two-electron species but rather occur via successive single-electron oxidation steps. Upon C - C or C - H fragmentation, the incipient alkane radical cations are trapped by nucleophiles.

Full text of DOI:10.1021/ja000193q

J. Am. Chem. Soc. 2000, 122, 7317-7326
7317
Oxidative Single-Electron Transfer Activation of σ-Bonds in Aliphatic
Halogenation Reactions
Andrey A. Fokin,*,† Peter R. Schreiner,*,‡§ Pavel A. Gunchenko,† Sergey A. Peleshanko,†
Tat′yana E. Shubina,† Sergey D. Isaev,† Pyotr V. Tarasenko,† Natalya I. Kulik,†
Hans-Martin Schiebel, and Alexander G. Yurchenko*,†
Contribution from the Department of Organic Chemistry, KieV Polytechnic Institute, pr. Pobedy 37,
252056 KieV, Ukraine, Georg-August UniVersity Go¨ttingen, Institute of Organic Chemistry, Tammannstr.
2, D-37077 Go¨ttingen, Germany, and Technical UniVersity Braunschweig,
Braunschweig, Institute of Organic Chemistry, Hagenring 30, D-38106, Germany
ReceiVed January 18, 2000
Abstract: The reactions of a series of structurally related large-ring propellanes with iodine monochloride
were studied experimentally and computationally. In the case of 1,3-dehydroadamantane (1) and [3.3.1]propellane
(2) free-radical addition was observed. [3.3.2]Propellane (3) and 3,6-dehydrohomoadamantane (4), which are
less prone to radical attack, selectively form products of formal double nucleophilic (oxidative) addition, e.g.,
dichloro (in ICl/CH2Cl2), dimethoxy (in ICl/CH3OH), and diacetamino (in ICl/CH3CN) derivatives under
otherwise identical conditions. Single-electron transfer pathways involving the alkane radical cations are proposed
for the activation step for aliphatic hydrocarbons with relatively low oxidation potentials such as cage alkanes.
Similar mechanisms are postulated for the activation of the tertiary C-H bonds of adamantane based on H/D-
kinetic isotope effect data. The latter compare well to the kH/kD value for hydrogen atom loss from the
adamantane radical cation (measured 2.78 ( 0.21 and computed 2.0) and differ considerably from the kinetic
isotope effects for electrophilic C-H bond activations (i.e., hydride abstraction) or for loss of a proton from
a hydrocarbon radical cation (kH/kD ) 1.0-1.4; computed 1.4). Hence, the reactions of alkanes with elementary
halogens and other weak electrophiles (but strong oxidizers) do not necessarily involve three-center
two-electron species but rather occur via successive single-electron oxidation steps. Upon C-C or C-H
fragmentation, the incipient alkane radical cations are trapped by nucleophiles.
Introduction
are known to have both electrophilic and oxidizing properties,
single electron transfer (SET) oxidations of hydrocarbons with
concomitant formation of radical cations followed by proton
(or hydrogen atom) loss14-17 or fragmentation18-22 have largely
been left unexplored. In on our previous experimental and
computational studies23-25 we found that SET pathways are
quite important if not decisive for alkanes with low ionization
potentials such as large-ring propellanes (C-C bond oxidation)
or adamantanes (C-H bond oxidation) in their reactions with
The selective activation and functionalization of alkanes,
despite extensive efforts, still is highly challenging and is
considered a “holy grail” in chemistry.1-6 Different methods
for alkane activation evolved, e.g., free radical reactions,
enzymatic transformations, as well as carbene or organometallic
insertions.5,7,8 Perhaps the most intriguing mechanistic proposals
are related to electrophilic alkane conversions believed to occur
via formation of three-center two-electron (3c-2e) transition
structures or intermediates (Scheme 1).9-13 Despite the fact that
many electrophilic reagents widely used in alkane activations
(11) Olah, G. A.; Farooq, O.; Prakash, G. K. S. ActiVation and
Functionalization of Alkanes; John Wiley & Sons: New York, 1989.
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Sons: New York, 1995.
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Chem. Soc. 1986, 108, 7727.
† Kiev Polytechnic Institute.
‡ Georg-August University Go¨ttingen.
§ Current address: Department of Chemistry, University of Georgia,
Athens, Georgia 30602-2556, USA.
Technical University Braunschweig.
(1) Bard, A. J.; Whitesides, G. M.; Zare, R. N.; McLafferty, F. W. Acc.
Chem. Res. 1995, 28, 92.
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& Sons Inc.: New York, 1989.
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Hydrocarbon ActiVation, Principles and Progress; VCH: Weinheim, 1990.
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A.; Yurchenko, A. G. Tetrahedron Lett. 1995, 4479.
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R.; Schreiner, P. R. Eur. J. Org. Chem. 1999, 855.
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A. J. Org. Chem. 1998, 62, 6494.
10.1021/ja000193q CCC: $19.00 © 2000 American Chemical Society
Published on Web 07/13/2000

7318 J. Am. Chem. Soc., Vol. 122, No. 30, 2000
Fokin et al.
Scheme 1. Electrophilic (formation of 3c-2e species) and Single-Electron Oxidation Pathways (i.e., through alkane radical
cations) for Aliphatic Hydrocarbon Functionalizationa
a These two pathways represent the two borderline cases of the reactivity spectrum whereby the first may be considered as an inner-sphere and
the second as an extreme case for an outer-sphere ET process.40
Scheme 2. Generalized Mechanistic Picture for Alkane C-C Bond Halogenations
nitrosonium (NO+) and nitronium (NO2+) electrophiles (e.g.,
Evidence for pathway b (electrophilic) comes from nucleo-
philic trapping of cationic intermediates in polar solvents. For
instance, the iodination or bromination of [1.1.1]propellane in
methanol involves the formation of the 3-halobicyclo[1.1.1]-
pent-1-yl cation.37 Electrophilic chlorination and bromination
of cyclopropane also appears to proceed via haloethyl ions.38,39
Elementary halogens also are oxidizing agents; the mecha-
nisms involving initial SET followed by formation of hydro-
carbon radical cations are depicted in pathway c. This mecha-
nism was proposed for the reaction of bicyclo[1.1.0]butane-1-
carbonitrile with bromine in methanol,41 but was later criticized
based on partial analysis of the thermodynamics of this system.30
The SET oxidation of strained alkanes with bromine was
claimed to be endergonic and slow.30
in the form of their salts, NO+BF4 and NO2+BF4-).
-
Mechanistic interpretations of polar C-H halogenation reac-
tions are often clouded by the inability to identify the nature of
the proposed transients (which may even be transition structures)
and the departing groups or atoms (e.g., H-, H•, or H+). As
cage hydrocarbon halogenations are an intriguing example, we
will first focus our attention on the mechanisms of σC-C-bond
halogenations which have been studied involving strained
propellanes26-28 and bicyclobutanes.29,30 Possible mechanistic
scenarios for the addition of elementary halogens to saturated
σC-C bonds are depicted in Scheme 2. Radical chain halogena-
tions (pathway a) normally occur in nonpolar solvents upon
photochemical or thermal initiation.31-33 Polyhalomethanes react
quickly with some small-ring propellanes also via free-radical
These mechanisms may be examined in more detail using
mixed halogens such as iodine monochloride (I+Cl-). This
reagent has successfully been used for mechanistic studies of
adamantane C-H halogenations42 and aromatic substitution
pathway a.34 Radical mechanisms also were proposed for some
- 35,36
other halogenating reagents such as PyH+Br3
.
(26) Ginsburg, D. Acc. Chem. Res. 1972, 5, 249.
(27) Tobe, Y. Propellanes. In Carbocyclic Cage Compounds, Chemistry
and Applications; Osawa, E., Yonemitsu, O., Eds.; VCH: New York, 1992.
(28) Szeimies, G. Bridgehead Olefins and Small Ring Propellanes. In
AdVances in Strain in Organic Chemistry; Halton, B., Ed.; JAI Press Ltd.:
London, 1992; Vol. 2, p 1.
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(30) Christl, M. Electrophilic Additions to Bicyclo[1.1.0]butanes. In
AdVances in Strain in Organic Chemistry; Halton, B., Ed.; JAI Press Ltd.:
London, 1995; Vol. 4, p 163.
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M.; Baklan, V. F. Tetrahedron Lett. 1986, 26, 1399.
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(33) Warner, P.; LaRose, R.; Schleis, T. Tetrahedron Lett. 1974, 1409.

OxidatiVe Single-Electron Transfer ActiVation of σ-Bonds
Scheme 3. Addition of ICl to Propellanes 1-4
J. Am. Chem. Soc., Vol. 122, No. 30, 2000 7319
reactions.43,44 In the latter case, it was shown that some aromatic
compounds with low ionization potentials undergo chlorination
rather than iodination, and this fact could only be attributed to
an SET oxidation of the hydrocarbon. Surprisingly, there is only
one study on the reactions of propellanes with mixed halogens,
namely the addition of I+Cl- to [1.1.1]propellane which resulted
in the formation of complex mixtures of halogenated com-
pounds.37
It was in this context that we began to examine the reactivity
of some large-ring propellanes (1-4) which are more stable
than [1.1.1]propellane avoiding side reactions such as fragmen-
tation and isomerization. These propellanes are pertinent
hydrocarbon models for studying the mechanisms of σC-C-bond
halogenations because the C-C bond reactivities can be varied
considerably by changing the ring size. Among other questions
addressed in the present paper, we will reveal details of C-H
halogenation mechanisms of adamantane45 and other cage
hydrocarbons.
Thus, propellanes 1-4 cover a wide range of σC-C-bond
reactivities with only minor changes in structure.25
Cyclopropane-containing propellanes 1 and 2 react with ICl
in CCl4, CH2Cl2, and THF with formation of complex mixtures
of halogenated products 5-12 (Scheme 3). These mixtures of
products as well as the formation of dimers 8 and 12 are clear
indications for a free-radical halogenation mechanism. This is
consistent with earlier observations that the bromination of 2
in the dark occurs via a free-radical pathway.32,33
In contrast, the addition reactions of ICl to 3 and 4 under
similar reaction conditions are highly selective as only dichloro
products 13 and 14 were found. This selectivity is not expected
for a radical mechanism (pathway a, Scheme 2). Formal addition
of two nucleophiles (Cl-) to the central C-C bonds provides
strong support for oxidative activation pathway c for 3 and 4.
As an example, Scheme 4 outlines SET from 4 to I+Cl- leading
to a radical ion pair of 4+• and I•Cl-. Nucleophilic trapping of
4+• produces radical A which may undergo further oxidation
to cation B, followed by a second nucleophilic addition.51,52 This
scheme is in accord with the observed 2:1 ICl to hydrocarbon
stoichiometry. Intermediate formation of radical A in the course
of the oxidative addition was confirmed by using BrCCl3 as a
radical trapping reagent: The halogenation of 4 by ICl in BrCCl3
was accompanied by formation of 15% of 3-bromo-6-chloro-
homoadamantane.
Results and Discussion
C-C Bond Halogenations. The reactivity of C-C bonds
varies widely in hydrocarbons 1-4 (Scheme 3). 1,3-Dehydro-
adamantane (1) with an inverted geometry46 at the quaternary
carbons is highly reactive and adds various reagents such as
proton acids,47 oxygen,48 and bromine48 at low temperatures.
[3.3.1]Propellane (2) is less reactive than 1 toward oxygen or
acetic acid, but could also be brominated with elementary
bromine at low temperatures.32,33 [3.3.2]Propellane (3) is known
to be reactive toward trifluoroacetic acid only under prolonged
heating.49 In contrast, 3,6-dehydrohomoadamantane (4) does
not react with oxygen, peroxides, or proton acids, but, as
adamantane, slowly reacts with liquid bromine upon heating.50
The reaction of 4 with ICl in nucleophilic solvents also
proceeds as a formal double nucleophilic addition with formation
of 3,6-dimethoxyhomoadamantane (15) in ICl/CH3OH and
3,6-diacetaminohomoadamantane (16) in ICl/CH3CN. Hence,
cationic intermediates are trapped by nucleophilic solvents
(Scheme 4) as previously observed for the oxidation of 4
with nitronium53 and nitrosonium24 reagents, under anodic
oxidation,54 and photooxidation.24 It is important to note that
(43) Hubig, S. M.; Jung, W.; Kochi, J. K. J. Org. Chem. 1994, 59, 6233.
(44) Turner, D. E.; O’Malley, R. F.; Sardella, D. J.; Barinelli, L. S.;
Kaul, P. J. Org. Chem. 1994, 59, 7335.
(45) Schleyer, P. v. R. My Thirty Years in Hydrocarbon Cages: From
Adamantane to Dodecahedrane. In Cage Hydrocarbons; Olah, G. A., Ed.;
Wiley: New York, 1990; p 1.
(50) Yurchenko, A. G.; Voroshenko, A. T.; Stepanov, F. N. J. Org. Chem.
(Engl. Trans.) 1970, 5, 188.
(51) Evans, J. F.; Blount, H. N. J. Org. Chem. 1976, 41, 516.
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4591.
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1979, 101, 6970.
(53) Fokin, A. A.; Gunchenko, P. A.; Kulik, N. I.; Iksanova, S. V.;
Krasutsky, P. A.; Gogoman, I. V.; Yurchenko, A. G. Tetrahedron 1996,
5857.
(48) Pincock, R. E.; Torupka, E. J. J. Am. Chem. Soc. 1969, 91, 4593.
(49) Bishop, R.; Landers, A. E. Aust. J. Chem. 1979, 32, 2675.
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A. G.; Krasutsky, P. A. Zh. Org. Khim. Russ. 1995, 31, 796.

7320 J. Am. Chem. Soc., Vol. 122, No. 30, 2000
Fokin et al.
Scheme 4. SET Mechanism for the Halogenation of 4 with ICla
a kf designates the rate constant for C-C bond fragmentation.
Scheme 5. Relative Reaction Energies for Vertical SET Oxidation and σC-C Bond Fragmentation for Propellanes 1-4 at
MP2/6-311+G**//MP2/6-31G*
SET from 1-4 to ICl is energetically favorable due to the
relatively low ionization potentials of these alkanes.25 The
vertical ionization potentials55 of 1 (8.35 eV), 2 (9.09 eV),
3 (9.59 eV), and 4 (9.41 eV)25 are much lower than the elec-
tron affinity of I+ (10.4 eV).56 This value presents an upper
limit but is probably a good approximation for the electron
affinities of (ICl)n clusters.5,7,8 The simplest model reaction
(IClH+ + e- f I• + HCl) to estimate the oxidative properties
of ICl is 257.1 kcal mol-1 (11.1 eV) exothermic (at B3LYP
with a MIDI!57 basis set for iodine and 6-31G* for hydrogen
and chlorine).
3 and 4 can be rationalized in terms of the pronounced
sluggishness of 3 and 4 toward radical reagents. The radical
addition to 1 and 2 is faster than SET oxidation with ICl; the
opposite is true for 3 and 4. As the electron transfer from the
hydrocarbon to the oxidizer is reversible (Scheme 4),58 the
efficiency of the oxidation depends on the relative rate of radical
cation fragmentation (kf) and competitive reverse SET. Ioniza-
tion from the propellane HOMO, located on the central C-C
bond of 3 and 4,25 leads to elongation of this “half-broken” bond
(adiabatic process) and is accompanied by strain decrease in
the partially distonic59 radical cation, making fragmentation
energetically favorable. Radical cations 3+• and 4+•, in fact, are
formed irreVersibly60-62 under adiabatic ionization of the
strained hydrocarbon, and oxidation proceeds efficiently. As
shown in Scheme 5, the oxidative fragmentation is more
The differences between the reactivities of cyclopropane-
containing propellanes 1 and 2 and their cyclobutane analogues
(55) Vertical IPs were computed for the neutral hydrocarbon geometries
where one electron was removed (i.e., a Franck-Condon state). As a
consequence, these structures are not stationary and only serve as models
for fast and reversible electron transfer in aliphatic hydrocarbons. This is
the reason these “structures” are put in brackets in Schemes 4 and 5.
(56) Eberson, L.; Radner, F. Acc. Chem. Res. 1987, 20, 53.
(57) Li, J.; Cramer, C. J.; Truhlar, D. G. Theor. Chem. Acc. 1998, 99,
192.
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1996, 37, 583.
(61) Gassman, P. G.; Hay, B. A. J. Am. Chem. Soc. 1986, 108, 4227.

OxidatiVe Single-Electron Transfer ActiVation of σ-Bonds
J. Am. Chem. Soc., Vol. 122, No. 30, 2000 7321
Scheme 6. Electrophilic and Oxidative Pathways for the Activation of a Tertiary C-H Bond of Adamantane
favorable for cyclobutane containing 3 and 4 due to larger
central C-C bond elongation and more effective strain decrease
in the resulting radical cations 3+• and 4+•.
possible pathway in the activation of methane and ethane with
relatively stable electrophiles such as NO+ involves direct
carbon atom attack; similar findings were also reported by
+
DePuy et al. for the reactions of BH2 with these hydro-
Hydrocarbon C-H Bond Halogenations. C-C bond
breaking is only one of the many fragmentation pathways of
hydrocarbon radical cations;63 others include C-H bond cleav-
age as observed for adamantane (17) and some other hydro-
carbons upon photooxidation64-67 or anodic oxidation.68-72 The
two principal polar mechanisms for the reactions of aliphatic
hydrocarbons with an electrophile (E+), i.e., via “hydride
abstraction” (a) and SET (b), are depicted in Scheme 6 for the
adamantane case study. The SET pathway for the activation of
carbons.79 In contrast, electrophilic attack of protonated
hydrogen peroxide H3O2+ (hydroperoxonium ion) on the tertiary
C-H bond of isobutane is a hydride abstraction according to
Bach and Su;80,81 Scheme 7 summarizes these results, computed
for adamantane.
Adamantane exothermically forms an initial complex (20,
-10.3 kcal mol-1) with the hydroperoxonium ion (Figure 1).
Such alkane-electrophile complexes were suggested compu-
tationally77,78 and verified experimentally.82 The transition
structure 21 for hydride abstraction from adamantane is
characterized by an only slightly elongated C-H bond (1.14 Å
+
17 with NO2 has been questioned by Olah,73 and an electro-
philic mechanism involving hydride abstraction as the rate-
limiting step was proposed instead (path a). In previous mech-
+
74
vs 1.11 Å in 20); the barrier for hydride abstraction with H3O2
anistic studies of adamantane C-H halogenations with Br2
is only 1.6 kcal mol-1; the computed H/D KIE of this
electrophilic reaction is very small (kH/kD ) 1.07) and reflects
the early character of the transition state.
and ICl42 electrophilic mechanisms also were proposed but never
conclusively demonstrated. As adamantane has a relatively low
ionization potential (experimental vertical IP 9.21-9.26 eV,75,76
the computed adiabatic IP at MP2 is 9.5 eV),24 SET oxidation
must not be excluded a priori.
Vanishingly low barriers for hydride transfer were also found
for the reactions of alkanes with carbocations.13 Computations
at DFT and MP2 levels indicate that the “formation of a stable
tight intermediate complex and decomposition of the complex
to the products” occurs “without actiVation energy”.83 As it
appears rather difficult to determine meaningful activation
barriers for these types of reactions, we used chemical ionization
mass spectrometry (CI-MS) to estimate the KIE for electrophilic
C-H bond activation by carbocations experimentally to dis-
tinguish between purely electrophilic and SET pathways. The
relative rates for hydride abstraction from the adamantane
bridgehead positions with the tert-butyl cation were determined
from the CI-MS data for adamantane, alkyladamantanes, and
their deuterated analogues using isobutane as the reagent gas
(see Experimental Section for details). These experiments indi-
cate that the KIEs for the electrophilic activation of the tertiary
Many aliphatic substitution mechanisms are too difficult to
be rationalized based on synthetic results only,3 as both
electrophilic and oxidative activation pathways are consistent
with the available synthetic data. Therefore, we undertook
studies utilizing H/D kinetic isotope effects (KIEs) to distinguish
between electrophilic and oxidative pathways. KIEs are excep-
tionally valuable in mechanistic studies, in particular in com-
bination with ab initio molecular orbital computations, which
allow a more detailed rationalization of the measured KIEs.
Electrophilic Activation of the Tertiary C-H Bond of
Adamantane. As shown previously by Schreiner et al.,77,78 one
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C-H bonds of adamantane indeed are quite low (kH/kD
)
1.05 ( 0.10) and in excellent agreement with our computed
+
KIEs for the reaction of adamantane with H3O2
.
(77) Schreiner, P. R.; Schleyer, P. v. R.; Schaefer, H. F., III J. Am. Chem.
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(75) Clark, T.; Knowx, T. M.; Mackle, H.; McKervey, M. A.; Rooney,
J. J. J. Am. Chem. Soc. 1975, 97, 3835.
(78) Schreiner, P. R.; Schleyer, P. v. R.; Schaefer, H. F., III J. Am. Chem.
Soc. 1995, 117, 453.
(79) DePuy, C. H.; Gareyev, R.; Hankin, J.; Davico, G. E.; Krempp,
M.; Damrauer, R. J. Am. Chem. Soc. 1998, 120, 5086.
(80) We found an analogous transition structure for hydride abstraction
+
from isobutane with the Cl3 cation, modeling the electrophilic reaction
with polarized dihalogen compounds. The geometry of the hydrocarbon
moiety in this TS and the reaction barriers are quite similar to that found
by Bach and Su for the hydroperoxonium ion reaction with isobutane.
(81) Bach, R. D.; Su, M.-D. J. Am. Chem. Soc. 1994, 116, 10103.
(82) Cacace, F.; de Petris, G.; Pepi, F. Proc. Natl. Acad. Sci. U.S.A. 1997,
94, 3507.
(83) Boronat, M.; Viruela, P.; Corma, A. J. Phys. Chem. B 1997, 101,
10069.
(76) Mateescu, G. D.; Worley, S. D. Tetrahedron Lett. 1972, 52, 5285.

7322 J. Am. Chem. Soc., Vol. 122, No. 30, 2000
Fokin et al.
Figure 1. MP2/6-31G* optimized geometries of the initial complex (20) and the transition structure for hydride abstraction (21) from adamantane
+
with H3O2
.
Scheme 7. Hydride Abstraction with the Hydroperoxonium Ion from a Tertiary C-H Bond of Adamantane {Relative Energies
in kcal mol-1 at MP2/6-311+G**//MP2/6-31G* + ∆ZPVE}
Scheme 8. Computed Hydrogen Loss from the Adamantane Radical Cation {Relative Energies in kcal mol-1 at MP2/
6-311+G**//MP2/6-31G* + ∆ZPVE}
This kH/kD value is quite different from the KIEs observed
for typical adamantane C-H substitution reactions with stable
electrophiles. The KIE for the bromination of adamantane in
Br2/CCl4 for 1,3,5,7-tetradeuterioadamantane vs adamantane is
3.9 ( 0.2. This value is similar to the one found previously for
adamantane nitroxylation (kH/kD ) 4.5 ( 0.3) with 100% nitric
acid.84 The KIEs for the reactions with charged nitrogen-
+
containing electrophiles (NO2 and NO+ salts in CH3CN) are
1.9-2.3.85
SET Activation of the Tertiary C-H Bond of Adaman-
Figure 2. MP2/6-31G* optimized geometries of the adamantane radical
tane. In contrast to the parent acyclic analogue isobutane, SET
cation (17•+) and the transition structure for hydrogen loss from the
adamantane radical cation (22).
oxidation of adamantane leads to a highly delocalized C3V-
symmetric radical cation (17+•) with one substantially elongated
C-H and three long C-C bonds (Scheme 8 and Figure 2).86-88
lose either a hydrogen or a proton. As expected, in the gas phase
the fragmentation of 17+• to the 1-adamantyl cation 18 and a
hydrogen atom (Scheme 8) is much more favorable than loss
of a proton (+13.8 vs +188.1 kcal mol-1, respectively). The
partially broken C-H bond elongates considerably90 (Figure
2) in the transition structure for hydrogen loss (22) and the
computed barrier is substantial (16.1 kcal mol-1 at MP2/6-
311+G**//MP2/6-31G* + ∆ZPVE(MP2/6-31G*). The com-
puted KIE for this reaction (kH/kD ) 2.0) is in agreement with
our electron impact mass spectrometry (EI-MS) data: Under
these conditions adamantane91 eliminates hydrogen atoms
exclusively from the bridgehead positions (the [M-H+] ion is
not observed in the EI-MS of 1,3,5,7-tetradeuterioadamantane)
Fragmentation of the tertiary C-H bond, which is partially
broken,89 is preferred, i.e., the adamantane radical cation can
(84) Klimochkin, J. N.; K., M. I. Zh. Org. Khim. 1988, 24, 557.
(85) Bach, R. D.; Holubka, J. W.; Badger, R. C.; Rajan, S. J. J. Am.
Chem. Soc. 1979, 101, 4416.
(86) There are some limitations in using isobutane as a model for C-H
activation of cage compounds such as adamantane. If electrophilic activation
proceeds via similar TSs, the mechanistic picture for oxidation reactions is
expected to be quite different. The isobutane radical cation is stable only
in Cs symmetry with one elongated C-C bond and shortened C-H bonds:
C-C bond fragmentation is favorable. The adamantane radical cation has
a stable C3V minimum with a long C-H bond and hydrogen loss occurs as
a one-step process.
(87) Bellville, D. J.; Bauld, N. L. J. Am. Chem. Soc. 1982, 104, 5700.
(88) Olivella, S.; Sole´, A.; McAdoo, D. J.; Griffin, L. L. J. Am. Chem.
Soc. 1994, 116, 11078.
(89) Toriyama, K.; Nunome, K.; Iwasaki, M. J. Phys. Chem. 1986, 90,
6836.
(90) Bally, T.; Sastry, G. N. J. Phys. Chem. A 1997, 101, 7923.
(91) Bezoari, M. D.; Kovacic, P.; Gadneux, A. R. Org. Mass Spectrom.
1996, 9, 507.

OxidatiVe Single-Electron Transfer ActiVation of σ-Bonds
J. Am. Chem. Soc., Vol. 122, No. 30, 2000 7323
Figure 3. B3LYP/6-31G* optimized geometries of the initial complex (23) and the transition structure for hydrogen exchange (26) of the adamantane
radical cation with H2O.
Figure 4. B3LYP/6-31G* optimized geometries of the initial complex (24) and the transition structure for proton migration (27) as well as acetonirtile
insertion product (28) for the reaction of the adamantane radical cation with CH3CN.
Scheme 9. Proton Transfer from the Adamantane Radical Cation to Water and Acetonitrile {Relative Energies in kcal mol-1 at
B3LYP/6-311+G**//B3LYP/6-31G* + ∆ZPVE}
and the ratio of [M-H]+ (for adamantane) and [M-D+]
(for 1,3,5,7-tetradeuterioadamantane) in the mass spectra reflects
the relative rates for the C-H vs C-D bond fragmentation
(kH/kD ) 2.78 ( 0.20)
As mentioned above, proton loss from the adamantane radical
cation is energetically highly unfavorable in the gas phase but
may readily occur in the condensed state due to the stabilization
of the proton.92,93 We evaluated the structures depicted in
Scheme 8 including one (acetonitrile) and up to three explicit
solvent molecules (water). The adamantane radical cation forms
an initial complex with a water (23, Figure 3 and Scheme 9)
and with an acetonitrile molecule (24, Figure 4 and Scheme 9);
the complexation exothermicities are substantial (-7.2 and
-12.8 kcal mol-1). The bridgehead C-H bond is elongated
considerably in these complexes relative to the unsolvated
radical cation 17+•. Proton migration from 17+• to water
(Scheme 9) is +43.7 kcal mol-1 endothermic; for acetonitrile
this process is less unfavorable (+19.9 kcal mol-1). Although
including just one solvent molecule in these computations is a
very crude model, it shows that hydrogen loss from the ada-
mantane radical cation with formation of protonated 1-hydroxy-
adamantane (25) is 14.3 kcal mol-1 less unfavorable than proton
loss. Clearly, these reactions are dominated by the exceptional
stability of tertiary 1-adamantyl systems both in the gas phase
and in the condensed state. This situation keeps changing until
three water molecules are included, at which point the two
(92) Albini, A.; Mella, M.; Freccero, M. Tetrahedron 1994, 50, 575.
(93) Lewis, F. D.; Zebrowski, B. E.; Correa, P. E. J. Am. Chem. Soc.
1984, 106, 187.

7324 J. Am. Chem. Soc., Vol. 122, No. 30, 2000
Fokin et al.
Scheme 10. Proposed Mechanism for the SET-Initiated C-H Activation of Adamantane with ICl
Table 1. Kinetic Isotope Effects for the Reaction of the
Bridgehead Adamantane C-H Bond under Various Conditions
reactions, hydrogen (4.9 kcal mol-1) or proton loss (-3.5 kcal
mol-1), both become close to thermoneutral.
reaction of
suggested
The transition structure for proton exchange with water (26)
in the adamantane radical cation (Figure 3) was located; the
barrier is 27.3 kcal mol-1. In contrast, transition structure 27
describes insertion of an acetonitrile molecule into the activated
C-H bond of the adamantane radical cation via proton
migration; the geometry of the adamantane moiety in transition
structure 27 is similar to that of the 1-adamantyl radical (19).
The resulting product structure 28 is 3.3 kcal mol-1 less stable
than the initial complex of acetonitrile with the adamantane
radical cation 24,94-96 but this energy difference lies well within
the error bars of our crude model. As 28 is able to stabilize the
radical cation internally through its π-system, the reaction of
17+• with acetonitrile is much more favorable than the reaction
with water.
The proton migration to acetonitrile has a barrier of 20.0 kcal
mol-1 (via 27) and the computed KIE for proton loss is small
(kH/kD ) 1.35) due to the nonlinear character of the participating
bonds in 27 (Figure 4). Such low KIEs were also observed
for the elimination of a proton from substituted aromatic
radical cations in acetonitrile (kH/kD ) 1.0 in pure CH3CN and
kH/kD ) 1.4 in a 4:1 mixture of CH2Cl2/CH3CN).97-100
It appears that only hydrogen atom loss from the adamantane
radical cation shows pronounced KIEs which are comparable
to those observed experimentally for reactions of adamantane
with electrophilic oxidizers (Table 1). This suggests single-
electron oxidation steps for these types of reactions, followed
by hydrogen atom loss from the radical cation and nucleophilic
capture of the carbocation thus formed.
adamantane with
KIE
1.07a
mode of reaction
+
H3O2
hydride abstraction
hydride abstraction
SET
SET
tert-butyl cation
1.05 ( 0.1
4.5 ( 0.384
1.9-2.385
3.9 ( 0.2
HNO3 (100%)
NO+ and NO2
+
Br2
SET
H loss from radical cation
2.78 ( 0.2b
SET follow-up reaction
a Computed value at MP2/6/31G*. b Computed (MP2/6-31G*)
value ) 2.0.
chlorides. The reaction of adamantane with ICl also leads to
1-chloroadamantane 29 as the sole product. Scheme 10 outlines
the mechanism we envisage for this reaction based on the
evidence presented in the present paper. Reversible SET to ICl101
is followed by slow hydrogen migration and HI elimination from
the radical ion complex; fast carbocation recombination with
the nucleophile gives 29.
To probe the existence of 1-adamantyl intermediates in
the course of the halogenation, the reaction of adamantane with
ICl was run in the presence of both cation and radical traps.
The chlorination with ICl in the 1-position of adamantane in
the radical trapping solvent BrCCl3
102,103
proceeds with 98%
selectivity. Formation of traces only of 1- and 2-bromo-
adamantane in a 2:1 ratio is a result of parallel free-radical
halogenation with BrCCl3.104 This clearly indicates that the
adamantane radical is not formed during the chlorination of
adamantane with I+Cl-.
The chlorination of adamantane in the presence of Et3-
(Dodecyl)N+Br- in CCl4 is accompanied by formation of 20%
of 1-bromoadamantane 30 as a result of ion pair C capture with
Br- (Scheme 10). The high KIEs for this reaction are strong
evidence against the formation of the adamantyl cation as a
result of electrophilic hydride abstraction through the halogens.
On the basis of our findings it is understandable that the
halogenations of propellanes 3 and 4 exclusively produce alkyl
(94) Adamantane photooxidation with 1,2,4,5-tetracyanobenzene (TCB)
in acetonitrile proceeds with intermediate formation of the adamantyl radical
cation; further fragmentation to the 1-adamantyl radical occurs via elimina-
tion of a proton. We studied the KIE of this reaction experimentally for
competitive adamantane and 1,3,5,7-tetradeuterioadamantane photooxidation
using Mella’s conditions (ref 96). The observed inverse KIE (0.90 ( 0.05)
shows that proton loss is not included into the rate-limiting step. A detailed
study will be published elsewhere.
(95) Mella, M.; Fagnoni, M.; Freccero, M.; Fasani, E.; Albini, A. Chem.
Soc. ReV. 1998, 27, 81.
(96) Mella, M.; Freccero, M.; Soldi, T.; Fasani, E.; Albini, A. J. Org.
Chem. 1996, 61, 1413.
(97) An alternative mechanism for the deprotonation of the adamantane
radical cation involving fast and reversible formation of 27 and further
elimination of CH3CNH+ cannot be excluded. Generally, it is difficult to
differentiate between two possible ways of proton loss form hydrocarbon
radical cations in the presence of a nucleophile, i.e., between direct proton
transfer to the nucleophile and nucleophilic addition-elimination reactions.
(98) Masnovi, J. M.; Sankararaman, S.; Kochi, J. K. J. Am. Chem. Soc.
1989, 111, 2263.
(99) Anne, A.; Fraoua, S.; Hapiot, P.; Moiroux, J.; Save`ant, J.-M. J. Am.
Chem. Soc. 1995, 117, 7412.
(100) Parker, V. D.; Chao, Y. T.; Zheng, G. J. Am. Chem. Soc. 1997,
119, 11390.
Conclusions
The present combined experimental/computational study
provides strong evidence for oxidative single-electron transfer
pathways in the functionalization of aliphatic hydrocarbons with
oxidizing electrophiles. While the highly reactive propellanes
1 and 2 react with halogens through a free-radical pathway, the
(101) Halogenation of adamantane and its derivatives is characterized
by high concentrational rate orders in halogen. For the bromination of
adamantane the formal reaction order in Br2 is 6.9; for the chlorination
with ICl this value is 3.5.
(102) Cook, G. K.; Mayer, J. M. J. Am. Chem. Soc. 1994, 116, 1855.
(103) Barton, D. H. R.; Crich, D.; Kretzschmar, G. J. Chem. Soc., Perkin
Trans. 1 1986, 39.
(104) Schreiner, P. R.; Lauenstein, O.; Kolomitsyn, I. V.; Nadi, S.; Fokin,
A. A. Angew. Chem. 1998, 110, 1993; Angew. Chem., Int. Ed. 1998, 37,
1895..

OxidatiVe Single-Electron Transfer ActiVation of σ-Bonds
J. Am. Chem. Soc., Vol. 122, No. 30, 2000 7325
and may suffer from symmetry breaking.110,111 The positive experience
in computing radical cation structures with DFT in other112-117 and
our groups24,25 favors this approach somewhat. It should be noted that
the differences in, for instance, the ZPVEs, between B3LYP and MP2
can be substantial as indicated for 17+•. This may be a peculiarity of
the degenerate C3V symmetry of this structure but emphasizes that great
care must be taken when dealing with radical cations. Additionally,
some radical cation structures, such as the TS for loss of a hydrogen
from the adamantyl radical cation, could not be located at the DFT
level. Structures 23-28 could only be optimized at the DFT level due
to their considerable size. Single point energies were evaluated utilizing
the 6-311+G** basis set. Harmonic vibrational frequencies were
computed to ascertain the nature of all stationary points (the number
of the imaginary modes, NIMAG, is 0 for minima and 1 for transition
structures). All relative energies are corrected for zero-point vibrational
energies (ZPVE). Kinetic isotope effects were calculated using the
differences in H and D vibrational frequencies as outlined in ref 118.
less reactive hydrocarbons 3 and 4 are oxidized in a stepwise
fashion. C-C bond fragmentation of the incipient radical cation
leads to strain decrease which is the main driving force for
effective σC-C bond oxidation of strained cyclic systems with
relatively stable electrophiles. A similar situation arises for
tertiary C-H bond halogenations of adamantane where elimina-
tion of a hydrogen atom from the radical cation leads to the
relatively stable 1-adamantyl cation.
The KIEs for C-H bond substitution were determined
experimentally and computationally to differentiate electrophilic
and oxidative activation pathways. Electrophilic hydride ab-
straction from a tertiary C-H bond of adamantane occurs
via an early transition structure and displays a low H/D KIE
(kH/kD ) 1.1). This is confirmed by similarly low experimental
KIEs for the reaction of adamantane and its alkyl-substituted
derivatives with the isobutyl cation in the gas phase (kH/kD )
1.05 ( 0.10). Proton migration from the hydrocarbon radical
cation to the nucleophilic solvent (e.g., CH3CN) occurs via
a late transition state, and also displays very low H/D KIEs
(kH/kD ) 1.0-1.4).
Experimental Section
General. Infrared spectra were recorded on a Perkin-Elmer 1600
series FT-IR spectrophotometer. NMR spectra were measured on
a Varian VXR-300 spectrometer at 300 (1H NMR) and 75 MHz
(13C NMR). Chemical shifts are reported in ppm and are referenced to
TMS as internal standard. Routine GC-MS data were obtained using a
Hewlett-Packard 5970A/5971A spectrometer (HP GC-MS capillary
column 50 m × 0.2 mm, Ultra 1, Silicone, 80-250 °C). Electron impact
(EI) (70 eV) and chemical ionization (CI) (isobutane) mass spectra were
recorded on a double focusing mass spectrometer Finnigan MAT-8430
with GC inlet (Carlo Erba HRGC-MS, capillary column 30 m × 32
mm, DB-5, 80-300 °C temperature program 6 deg min-1).
Hydrogen atom loss from the adamantane radical cation (i.e.
formation of the relatively stable 1-adamantyl cation) shows
considerably higher KIEs. This was studied by means of electron
impact ionization techniques (kH/kD ) 2.78 ( 0.20) and ab initio
computations (kH/kD ) 2.0). These KIEs are consistent with
experimental data for the reactions of adamantane with elec-
trophilic reagents. The resulting carbocationic intermediates are
trapped by nucleophiles leading to the products.
Our results demonstrate and emphasize that the activation
of moderately strong C-C and tertiary C-H bonds with
elementary halogens or other weak to moderate electrophiles
does not follow the traditional electrophilic pathway which
involves 3c-2e bonding situations. Instead, single-electron
oxidations lead to alkane radical cations which undergo C-C
or C-H bond cleavage.
Materials. All commercial reagents were ACS reagent grade and
were used without further purification. Propellanes 1 and 2 were
prepared from 1,3-dibromoadamantane119 and 1,5-dibromobicyclo[3.3.1]-
nonane,120 respectively, via debromination with Na/K alloy in diethyl
ether and then sublimed in vacuo at 30 °C. The original procedure
was used for the preparation of 3,6-dihydrohomoadamantane (3);50
[3.3.2]propellane49 was prepared by photocyclization of 1,5-dimethyl-
enecyclooctane in diethyl ether in the presence of Cu2I2. All syntheses
were carried out under argon atmosphere.
Reaction of 1,3-dehydroadamantane (1) with ICl: To a solution
of 500 mg (3.7 mmol) of 1 in 5 mL of CH2Cl2 at 0 °C was added
dropwise a solution of 600 mg (3.7 mmol) of ICl in 10 mL of CH2Cl2
until the color persisted. The reaction mixture was diluted with aqueous
Na2SO3. The residue was extracted with CH2Cl2 (3 × 10 mL), washed
with water, and dried over Na2SO4; excess CH2Cl2was removed. The
reaction mixture (930 mg) was analyzed by GC-MS and showed the
following main EI peaks:121 1,3-diiodoadamantane (7, 45%)-388 (1%),
261 (100%), 134 (15%), 91 (20%); 1-chloro-3-iodoadamantane (5, 20%)
Computational Methods
Geometries were fully optimized at the MP2/6-31G* and B3LYP/
6-31G* levels of theory (unrestricted wave functions were used for
open-shell species) as implemented in the Gaussian 94105,106 and
Gaussian 98107 program packages. We utilized two different levels of
theory because it is not yet clear which of the two is more appropriate
for treating (large) radical cation systems. While MP2 sometimes suffers
from spin contamination (our spin operator expectation values ( S2 )
were in the range of 0.750-0.763), DFT ( S2 ) 0.750-0.753)
sometimes does not do well for charge/spin separated systems,90,108,109
(108) Braida, B.; Hiberty, P. C.; Savin, A. J. Phys. Chem. A 1998, 102,
7872.
(109) Sodupe, N.; Bertran, J.; Rodriguez-Santiago, L.; Baerenz, E. J. J.
Phys. Chem. A 1999, 103, 166.
(110) Rauhut, G.; Clark, T. J. Chem. Soc., Faraday Trans 1994, 90, 1783.
(111) Rauhut, G.; Clark, T. J. Am. Chem. Soc. 1993, 115, 9127.
(112) Oxgaard, J.; Wiest, O. J. Am. Chem. Soc. 1999, 121, 11531.
(113) Wang, J. H.; Becke, A. D.; Smith, V. H. J. Chem. Phys. 1995,
102, 3477.
(114) Laming, G. J.; Handy, N. C.; Amos, R. D. Mol. Phys. 1993, 80,
1121.
(105) Gaussian 94, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Gill,
P. M. W.; Johnson, B. G.; Robb, M. A.; Cheeseman, J. R.; Keith, T.;
Petersson, G. A.; Montgomery, J. A.; Raghavachari, K.; Al-Laham, M. A.;
Zakrzewski, V. G.; Ortiz, J. V.; Foresman, J. B.; Cioslowski, J.; Stefanov,
B. B.; Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala, P. Y.; Chen,
W.; Wong, M. W.; Andres, J. L.; Replogle, E. S.; Gomperts, R.; Martin,
R. L.; Fox, D. J.; Binkley, J. S.; Defrees, D. J.; Baker, J.; Stewart, J. P.;
Head-Gordon, M.; Gonzalez, C.; Pople, J. A., Gaussian, Inc., 1995, Revision
E.2.
(106) Foresman, J. B.; Frisch, Æ. Exploring Chemistry with Electronic
Structure Methods, 2nd. ed.; Gaussian, Inc.: Pittsburgh, 1996.
(107) Gaussian 98, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.;
Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.;
Montgomery, J. A.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam,
J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.;
Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.;
Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.;
Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman,
J. B.; Cioslowsk, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.;
Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith,
T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.;
Challacombe, M.; Gill, P. M. W.; Johnson, B. G.; Chen, W.; Wong, M.
W.; Andres, J. L.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A., Gaussian
Inc., 1998, Version A.5.
(115) Clark, T. Top. Curr. Chem. 1996, 177, 1.
(116) Murray, C. W.; Handy, N. C. J. Chem. Phys. 1992, 97, 6509.
(117) Ma, N. L.; Smith, B. J.; Pople, J. A.; Radom, L. J. Am. Chem.
Soc. 1991, 113, 7903.
(118) Melander, L.; Saunders, W. H., Jr. Reaction Rates of Isotopic
Molecules; John Wiley & Sons: New York, 1980.
(119) 1,3-Dibromoadamantane was prepared with 85% yield via
bromination of adamantane in the presence of catalytic amounts of FeBr3
under reflux in liquid bromine (Lichotvorik, I. R.; Dovgan’, N. L.;
Danilenko, G. I. Zh. Org. Khim. 1977, 13, 897).
(120) 1,5-Dibromobicyclo[3.3.1]nonane was prepared from 1,5-di-
hydroxybicyclo[3.3.1]nonane (Klimochkin, Yu. N.; Zhilkina, E. O.;
Abramov, O. V.; Moiseev, I. K. Zh. Org. Khim. 1993, 29, 1358) with PBr3
in CCl4.

7326 J. Am. Chem. Soc., Vol. 122, No. 30, 2000
Fokin et al.
296 (1%, [M]+•), 261 (1%), 169 (100%), 133 (50%), 91 (50%); 1,3-
dichloradamantane (6, 10%)122 204 (3%), 169 (100%), 133 (3%), 91
(15%); and several compounds (indicative of a radical process) of low
overall yield (5%) formally corresponding to the elemental composition
of 1-iodo-(3-chloradamant-1-yl)-adamantane (8) 260 (100%), 225
(30%), 169 (60%), 133 (35%), 107 (30%), 91 (20%).
Reaction of [3.3.2]propellane (3) with ICl: From 75 mg (0.54
mmol) of 3 and 280 mg of ICl (1.72 mmol) in 3 mL of CH2Cl2
following the above procedure for the chlorination of 4 was obtained
108 mg (90%) of 1,5-dichlorobicyclo[3.3.2]decane (13). The 1H NMR
spectrum was identical with the one described previously.125 13C
NMR: 34.99, 40.93, 42.63, 72.30. MS: 171 (15%), 157 (75%), 121
(100%), 93 (63%), 79 (63%), 67 (27%), 53 (24%).
Reaction of [3.3.1]propellane (2) with ICl: From 100 mg (0.82
mmol) of 2 in 1 mL of CH2Cl2 with 134 mg (0.83 mmol) of ICl in 2
mL of CH2Cl2 according to the above procedure was obtained 195 mg
of colorless liquid. Main components of the reaction mixture from
GC-MS data: 1-chloro-3-iodobicyclo[3.3.1]nonane (9, 25%) 157 (20%),
121 (100%), 93 (60%), 79 (75%), 67 (25%); 1,5-dichlorbicyclo[3.3.1]-
nonane123 (10, 25%) 192 (3%), 157 (100%), 121 (85%), 116 (25%),
92 (40%), 79 (58%); 1,5-diiodobicyclo[3.3.1]nonane (11, 15%) 249
(1%), 121 (100%), 93 (55%), 79 (70%), 67 (31%); 1-iodo-(5-
chlorobicyclo[3.3.1]non-1-yl)bicyclo[3.3.1]nonane (12, 17%) 249 (1%),
157 (95%), 121 (100%), 93 (80%), 79 (90%), 68 (30%), 53 (20%).
Reaction of 3,6-dehydrohomoadamantane (4) with ICl: (a) A
solution of 180 mg (1.1 mmol) of ICl in 2 mL of CH2Cl2 was added
dropwise to a solution of 80 mg (0.54 mmol) of 4 in 1 mL of CH2Cl2
at 20 °C and the mixture was stirred for 1 h, then diluted with an
aqueous solution of Na2SO3. The residue was extracted with CH2Cl2
(3 × 5 mL), the extracts were washed with water and dried over
Na2SO4; excess CH2Cl2 was removed. The mixture was filtered
through silica (hexane) and 108 mg (0.49 mmol, 90%) of 3,6-
dichlorohomoadamantane 14 was obtained. The NMR and IR spectral
data for 14 were identical with literature data.123 (b) From 80 mg of 4,
180 mg of ICl in 3 mL of CBrCl3 according to procedure a after
removing of BrCCl3 in vacuo was obtained 135 mg of a colorless oil.
The GC-MS indicated that the reaction mixture contained 67% of 14
(MS and retention time were identical with standard sample) and 15%
of 3-bromo-6-chlorohomoadamantane: 227 (1%, [M]+•), 183 (100%),
147 (25%), 105 (25%), 91 (44%), 79 (20%), 77 (20%), 39 (28%).
3,6-Dimethoxyhomoadamantane (15): A solution of 2.75 g (16.9
mmol) of ICl in 5 mL of CH3OH was added dropwisely to a solution
of 250 mg (1.69 mmol) of 4 in 5 mL of CH3OH at 30 °C and the
mixture was stirred for 50 h, then quenched with an aqueous solution
of Na2SO3; CH3OH was removed in vacuo. The residue was extracted
with HCCl3 (3 × 20 mL), the extract was washed with water and dried
over Na2SO4, and HCCl3 was removed. The mixture was filtered
through silica (ether-hexane 1:2) and 225 mg (63%) of 3,6-dimethoxy-
homoadamantane 15 was obtained; 1H NMR, 13C NMR, and IR spectra
were identical with the ones described by Israel and Murray.124 MS:
210 (5%, [M]+•), 179 (20%), 125 (100%), 109 (70%), 91 (22%), 79
(25%), 77 (23%), 55 (23%), 53 (21%). Found: C, 74.15; H, 10.64.
Calcd for C13H22O2: C, 74.24; H, 10.55.
Kinetic isotope effect MS measurements: (a) KIE of hydrogen
loss from 17+•. Kinetic isotope effects of hydrogen loss from the
adamantane radical cation were measured for adamantane (AdH4) and
1,3,5,7-tetradeuterioadamantane (AdD4) fragmentation upon electron
impact ionization. KIEs were calculated as the relative abundance of
the [M - 1]+ ion in the MS spectrum of AdH4 and of [M - 2]+ in
the spectrum of AdD4. The intensities of the ion peaks were corrected
for 13C isotope abundance (1.1% of 13C). The KIE for hydrogen loss
(2.78 ( 0.20) was calculated from multiple series of MS measurements.
(b) KIE of hydride abstraction from 17. Isobutane was used as the
reagent gas for chemical ionization of AdH4 and AdD4. AdD4 CI mass
spectrum corrected to 13C abundance: 140 (90.05%), 139 (101.63%),
138 (85.64%). AdH4 mass CI-MS corrected to 13C abundance: 136
(15.65%), 135 (110.20%). The fraction of ions resulting from the
elimination of secondary hydrogens from adamantane (0.3665) was
calculated as I139/(I140 + I139 + I138), where I is the 13C corrected
abundance of ions in the CI-MS of AdD4; the fraction of ions M-Hsec
for AdH4 was calculated as 0.3665(I136 + I135) ) 47.22. The fraction
of the ions M-Htert is (110.20 - 47.22) ) 62.98. Hence, the statistically
corrected hydride abstraction rate from tertiary and secondary positions
of adamantane is (12/4)(62.98/47.22) ) 4.00. The same procedure
for the separation of the M-Htert from the M-Hsec ion fractions
was used for different bridgehead methyl substituted adamantanes and
their deuterated counterparts. KIE ) 1.05 ( 0.10 was computed as
(IM-Htert/ IM-D) in multiple series of CI-MS experiments.
Kinetics of liquid-phase bromination of adamantane: The kinetics
of adamantane bromination was studied in Br2/CCl4 mixtures (concen-
trations of Br2 varied from 9 to 15 M). The reactant and product
concentrations were followed by GC. The rate constant for adamantane
bromination shows nonlinear dependence of the initial bromine
concentrations. The pseudo-first-order rate constants were used for KIE
measurements. In a typical kinetic experiment both for adamantane
and 1,3,5,7-tetradeuterioadamantane [AdH(D)]0 ) 0.2 mol L-1
,
[Br2]0 ) 13.4 mol L-1, and [CCl4]0 ) 5.6 mol L-1, the pseudo-first-
order bromination rate constants were kH ) 0.62 ( 0.03 s-1 and kD
0.159 ( 0.008 s-1 at 25 °C.
)
Acknowledgment. This paper is dedicated to Professor Paul
von Rague´ Schleyer for his outstanding contributions to organic
chemistry and on the occasion of 70th birthday. This work was
supported by the Fundamental Research Foundation of the
Ukraine and the Volkswagenstiftung (Grant I/74 614). A.A.F.
is grateful to the Alexander von Humboldt Foundation for a
fellowship. P.R.S. thanks the Deutsche Forschungsgemeinschaft
and Prof. A. de Meijere for continuing support. We acknowledge
generous allotments of supercomputer time at the Ho¨chstleis-
tungsrechenzentrum Stuttgart (HLRS).
3,6-Diacetaminohomoadamantane (16): A solution of 692 mg
(4.26 mmol) of ICl in 3 mL of CH3CN was added dropwise to a solution
of 107 mg (0.72 mmol) of 3 in 5 mL of CH3CN at 20 °C and the
mixture was stirred for 1 h, then diluted with an aqueous solution of
Na2SO3. The residue was extracted by HCCl3 (3 × 5 mL), the extract
was washed with water and dried over Na2SO4, and HCCl3 was
removed. The mixture was filtered through silica (ether-methanol 9:1).
The spectral data for the 30 mg (15%) of isolated 16 were identical
with those described earlier.23
Supporting Information Available: Tables with absolute
energies and x,y,z-coordinates of all computed structures (PDF).
This material is available free of charge via the Internet at
http://pubs.acs.org.
(121) Standard samples of 1-iodo-3-chloro- and 1,3-diiodoadamantanes
were prepared using a multiphase halogenation procedure discribed in the
following: Schreiner, P. R.; Lauenstein, O.; Butova, E. D.; Fokin, A. A.
Angew. Chem., Int. Ed. Engl. 1999, 38, 2786.
(122) Hamill, H.; Karim, A.; McKervey, M. A. Tetrahedron 1971, 27,
4317.
(123) Fokin, A. A.; Gunchenko, P. A.; Tkachenko, B. A.; Butova, E.
D.; Yurchenko, A. G. Tetrahedron Lett. 1997, 38, 639.
(124) Israel, R. J.; Murray, R. K., Jr. J. Org. Chem. 1983, 48, 4701.
JA000193Q
(125) Doyle, M.; Hafler, R.; Parker, W. J. Chem. Soc., Perkin Trans. 1
1977, 364.