EPR support for the ketyl radical-anion "triggered" [3,3]-sigmatropic rearrangement

Article abstract of DOI:10.1021/jo0257748

New physical evidence to support a ketyl radicalanion mechanism for the [3,3]-sigmatropic rearrangement is presented. With use of EPR spectroscopy, spectra are observed that can be attributed to 8, an acyl radical-anion species resulting from a [3,3]-rear

Full text of DOI:10.1021/jo0257748

SCHEME 1
EP R Su p p or t for th e Ketyl Ra d ica l-An ion
“Tr igger ed ” [3,3]-Sigm a tr op ic
Rea r r a n gem en t
Eric J . Enholm,*,† Merle A. Battiste,† Maria Gallagher,†
Kelley M. Moran,† Angelo Alberti,*,‡
Maurizio Guerra,‡ and Dante Macciantelli‡
Department of Chemistry, University of Florida,
Gainesville, Florida 32611, and ICoCEA, Area della
Recerca, Via P. Gobetti 101:I-40129, Bologna, Italy
enholm@chem.ufl.edu; aalberti@area.bo.cnr.it.
Received March 29, 2002
Abstr a ct: New physical evidence to support a ketyl radical-
anion mechanism for the [3,3]-sigmatropic rearrangement
is presented. With use of EPR spectroscopy, spectra are
observed that can be attributed to 8, an acyl radical-anion
species resulting from a [3,3]-rearrangement; this also
functions as a key intermediate in the process. The spectrum
of an additional paramagnetic species resulting from further
addition of tin-centered radicals to the reaction product was
also observed.
SCHEME 2
The [3,3]-sigmatropic shift is a versatile rearrangement
used extensively in organic synthesis.1 It is also well-
established that an anionic or cationic charge can ac-
celerate the rate of this reaction.2 Acceleration due to a
radical-anion, however, has only recently been proposed
via a metal-associated ketyl species.3 In the presence of
a radical initiator, enone 1 and tributyltin hydride form
the intermediate radical 2 T 3 that, because of the
polarization of the O-Sn bond, can also be viewed as the
radical ion pair 2′ T 3′, where formal negative and
positive charges are localized on the oxygen and the
Group 14 metal, respectively (see Scheme 1). The allylic
O-stannyl ketyl is a resonance-stabilized radical that can
independently undergo both radical and anionic reac-
tions.3
In particular, these intermediates can be used to
“trigger” a Claisen-type [3,3]-sigmatropic shift. When 4
is treated with tin hydride under standard thermal
radical conditions, radical-anion 5 is initially formed,
which subsequently rearranges to alcohol 6, the driving
force of the latter process being the formation of the
strong sp2 ketone bond in 6 (see Scheme 1). As outlined
in Scheme 2, two mechanistic scenarios, differing mostly
for the timing of events, can be envisioned for this
reaction. Both mechanisms involve the initial formation
of the allylic O-stannyl ketyl intermediate 5. Once this
species has been formed, the two paths bifurcate follow-
ing either an anionic mechanism going through species
5 f 7 f 9 f 64 or a radical-anion mechanism going
through species 5 f 8 f 9 f 6.3 In the former mecha-
nism, a hydrogen atom transfer occurs first in 5 f 7,
followed by the [3,3]-rearrangement of 7 f 9. On the
other hand, in the radical-anion mechanism, the [3,3]-
rearrangement 5 f 8 occurs first, being subsequently
followed by the hydrogen atom transfer. We now favor
the latter pathway, which represents an entirely new
mechanistic path for the [3,3] rearrangement, based on
new EPR evidence (vide infra).
With the aim to ascertain the actual pathway followed
by the reaction, we decided to try and observe 8 by
spectroscopic means. Since this radical intermediate is
not a possibility in the anionic mechanism, its detection
would strongly support the radical-anion pathway. We
therefore repeated the reaction between 4 and tin hy-
drides inside the cavity of an EPR spectrometer5 to
intercept and identify any intervening radical species. In
this manner, an argon-purged tert-butylbenzene solution
of compound 4 was heated inside the cavity of an EPR
spectrometer in the presence of either Ph3SnH or n-Bu3-
† University of Florida.
‡ ICoCEA.
(1) Wipf, P. In Comprehensive Organic Synthesis; Trost, B. M., Ed.;
Pergamon Press: New York, 1991; Chapter 8.3, p 999.
(2) Chubert, P. S.; Srebnik, M. Aldrichimica Acta 1993, 26, 17.
(3) Enholm, E. J .; Moran, K. M.; Whitley, P. E.; Battiste, M. A. J .
Am. Chem. Soc. 1998, 120, 3807.
(4) Curran, D. P.; Nishii, Y. J . Am. Chem. Soc. 1999, 121, 8955.
10.1021/jo0257748 CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/13/2002
J . Org. Chem. 2002, 67, 6579-6581
6579

F IGURE 2. Resonance forms of 8: experiment, R ) n-butyl;
DFT calculations, R ) H.
render equivalent the two hydrogen atoms adjacent to
the allylic carbon in position 4. Consistent with this
assignment, as the temperature is lowered, the triplet
approximates a doublet of doublets [a(1HR) ) 0.901 mT,
a(1Hâ) ) 0.472 mT, and a(1Hâ) ) 2.332 mT] indicating
that, although the conformational interchange of the six-
membered ring is not completely frozen out, the two
hydrogen atoms in position 4 are magnetically non-
equivalent. The presence of paramagnetic impurities
combined with the rather low intensity of the spectra did
not allow an accurate kinetic study of the conformational
motion of the six-member ring.
The values of the splittings measured for 8 were
compared to those reported for structurally related
radicals8 and our somewhat narrower hfs constants can
be supported by two lines of reasoning. First, a consid-
eration of the three resonance forms 8a , 8b, and 8c
unique to radical 8 can be envisioned, as shown in Figure
2. Thus, the resonance contribution of structure 8c, with
little spin density on the ring carbons, leads to splittings
readily in line with our observations. Second, the split-
tings for model compound 8c (R ) H) were briefly
checked by means of calculation studies by using the DFT
method at the B3LYP/6-311G*/UHF/6-31G* level, using
the Gausssion 98 system of programs.9 For the Sn atom
the LANL2DZ pseudopotential was used along with a d
polarization function. The corresponding hfs constants
for radical 8c were computed to be very small, i.e., 0.13,
0.11, and 0.24 mT, respectively, since in this species the
unpaired electron is mostly localized on the oxygen atom.
Though this resonance contributor was evaluated sepa-
rately here, collectively, the three species as resonance
contributors should indeed lead to hfs constant values
in agreement with the present experiments. The contri-
bution of resonance structure 8b to the system would also
nicely account for the ca. 0.76 mT hyperfine splitting
measured for the tin atom, a small value when consider-
ing that the A0 for tin exceeds 1.5 T.10 It should be
F IGURE 1. EPR spectra observed after thermal reaction of
4 with Ph3SnH in the presence of AIBN at (a) 353 K and (b)
after cooling to 273 K: O, radical 8; 4, tin satellites of radical
8; 2, 1,2-cyclohexanedione radical anion; and b, radical 10.
SnH and a small amount of AIBN. In both cases the
observed spectra were very similar and exhibited a
marked temperature dependence. At high temperature
(T g 353 K) the spectrum (see Figure 1a) was dominated
by a triplet of doublets [a(1HR) ) 1.059 mT, a(2Hâ) )
1.367 mT, a(217/219Sn) ) 0.76 mT, g ) 2.00405], the central
lines of the triplets being somewhat broader and less
intense than expected. A weak additional quintet [a(4H)
) 1.228 mT, g ) 2.00426] could also be observed, which
we tentatively attribute to the radical anion of 1,2-
cyclohexanedione6 as its corresponding O-stannyl ketyl
radical-anion.
On the basis of the spectral parameters,7 we assign this
spectrum to radical 8, where the conformational inter-
change of the six-member ring is “nearly” fast enough to
(5) EPR spectra were recorded on an upgraded Bruker ER200D/
ESP 300 spectrometer equipped with a NMR gaussmeter for the
calibration of the field, a frequency counter for the determination of
g-factors that were corrected with respect to that of perylene radical
cation in concentrated sulfuric acid, and with standard variable
temperature accessories. In a typical experiment an argon-purged tert-
butylbenzene solution of ketone 4 and either triphenyl or tributyl tin
hydride was added with a small amount of AIBN and heated to 323
K. Once the radicals had been formed, spectra could be recorded in
the temperature range 373-273K. Almost identical spectra were
observed by photolysis of solutions where AIBN had been replaced with
di-tert-butylperoxide. Similar but less resolved spectra were also
detected by photolysis of solutions of 4 and hexabutylditin.
(6) (a) Russell, G. A.; Osuch, C. E. J . Am. Chem. Soc. 1978, 100,
5979. (b) We attribute the formation of this radical-anion species at
higher temperatures to an interesting thermal elimination of tribut-
ylallylstannane from compound 9 (vide supra, Scheme 3) to form 1,2-
cyclohexanedione. This dione next reacts a second time with tributyltin
radical. Importantly, this semidione radical is not observed at lower
temperatures, thus rendering its formation by a competing radical or
anionic process unlikely.
(8) Landolt-Βo¨rnstein, New Series. Magnetic Properties of Free
Radicals; Fischer, H., Hellwege, K.-H., Eds.; Springer-Verlag: Heidel-
berg, Germany, 1977; Group II, Vol. 9, Part b. Landolt-Βo¨rnstein, New
Series. Magnetic Properties of Free Radicals; Fischer, H., Ed.; Springer-
Verlag: Heidelberg, Germany, 1987; Group II, Vol. 17, Part c.
(9) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J . R.; Zakrzewski, V. G.; Montgomery, J . A.,
J r.; 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.; Cioslowski, 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.; J ohnson, B. G.; Chen,
W.; Wong, M. W.; Andres, J . L.; Head-Gordon, M.; Replogle, E. S.;
Pople, J . A. Gaussian 98, Revision A7; Gaussian Inc.: Pittsburgh, PA,
1998.
(7) Hudson, A.; Waterman, D.; Della Bona, M. A.; Alberti, A.; Altieri,
A.; Benaglia, M.; Macciantelli, D. J . Chem. Soc., Perkin Trans. 2 1998,
2255.
(10) Morton, R. J .; Preston, K. F. J . Magn. Reson. 1978, 30, 577.
6580 J . Org. Chem., Vol. 67, No. 18, 2002

SCHEME 3
mentioned that DFT calculations predict radical 8a to
be more stable than 8c by ca. 15 kcal mol-1, although
the actual energy difference might be somewhat smaller
because DFT methods favor π-delocalized vs σ-delocalized
radicals.11
Besides these interesting features of this spectral
pattern, as the temperature was lowered, an additional
doublet of doublets originating from a different species
could also be clearly identified [a(1H) ) 1.212 mT, a(1H)
) 1.555 mT, g ) 2.00400]. We assign these signals to
radical 10,7 most likely resulting from addition of tin-
centered radicals to the reaction product 9 (see Scheme
3).9 This radical species is not observed at higher tem-
peratures presumably due to the reversibility depicted
(Scheme 3) or to decomposition.6
chemical evidence,3 lends convincing support to the
radical anion mechanism, proceeding through species 5
f 8 f 9 f 6. The ketyl radical anion mechanism
proposed above for a new type of [3,3]-sigmatropic
rearrangement is supported by EPR spectroscopy with
the spectra observed clearly attributed to radical-anion
species 8, a key intermediate in the process.
Ack n ow led gm en t. We gratefully acknowledge sup-
port by the National Science Foundation (grant CHE-
0111210) for this work.
In conclusion, the observation and identification of
radical 8, along with the previously mentioned pieces of
(11) Guerra, M. Theor. Chem. Acc. 2000, 104, 455.
J O0257748
J . Org. Chem, Vol. 67, No. 18, 2002 6581