Phenyl bridging in ring-substituted cumyloxyl radicals. a product and time-resolved kinetic study

Article abstract of DOI:10.1021/ol900635z

The reactivity of cumyloxyl radicals bearing cyclopropyl and 2,2-diphenylcyclopropyl groups in the para position has been investigated. Depending on radical structure, products deriving from C-C β-scission and/or cyclopropyl ring-opening are observed, sup

Full text of DOI:10.1021/ol900635z

ORGANIC
LETTERS
2009
Vol. 11, No. 11
2453-2456
Phenyl Bridging in Ring-Substituted
Cumyloxyl Radicals. A Product and
Time-Resolved Kinetic Study†
Michela Salamone, Massimo Bietti,* Alessandra Calcagni, and Giacomo Gente
Dipartimento di Scienze e Tecnologie Chimiche, UniVersita` “Tor Vergata”,
Via della Ricerca Scientifica, 1 I-00133 Rome, Italy
bietti@uniroma2.it
Received April 3, 2009
ABSTRACT
The reactivity of cumyloxyl radicals bearing cyclopropyl and 2,2-diphenylcyclopropyl groups in the para position has been investigated. Depending
on radical structure, products deriving from C-C ꢀ-scission and/or cyclopropyl ring-opening are observed, supporting the hypothesis that
cumyloxyl (and, more generally, arylcarbinyloxyl) radicals exist in equilibrium with 1-oxaspiro[2,5]octadienyl radicals, in full agreement with
the previously proposed mechanism for the O-neophyl rearrangement of 1,1-diarylalkoxyl radicals.
The 1,2-migration of an aryl group in arylcarbinyloxyl
radicals (O-neophyl rearrangement) has been the subject of
Scheme 1
several studies.1-3 This process, observed for radicals bearing
two or three aryl groups on the R-carbon, converts an oxygen
radical into a carbon radical.
Recently, theoretical studies provided convincing support
to the hypothesis that the O-neophyl rearrangement of 1,1-
diarylalkoxyl radicals proceeds through the reversible forma-
tion of an intermediate 1-oxaspiro[2,5]octadienyl radical
bridged radical (Scheme 2). However, no evidence in this
respect is presently available. The cumyloxyl radical is
known to undergo C-CH3 ꢀ-scission as the exclusive
(Scheme 1).4,5
According to this picture, it is reasonable to expect that
the cumyloxyl radical also exists in equilibrium with a
† Dedicated to Keith U. Ingold on the occasion of his 80th birthday.
(1) Ingold, K. U.; Smeu, M.; DiLabio, G. A. J. Org. Chem. 2006, 71,
Scheme 2
9906–9908
.
(2) (a) Bietti, M.; Salamone, M. J. Org. Chem. 2005, 70, 10603–10606.
(b) Aureliano Antunes, C. S.; Bietti, M.; Ercolani, G.; Lanzalunga, O.;
Salamone, M. J. Org. Chem. 2005, 70, 3884–3891
.
(3) Studer, A.; Bossart, M. Tetrahedron 2001, 57, 9649–9667
.
(4) Bietti, M.; Ercolani, G.; Salamone, M. J. Org. Chem. 2007, 72, 4515–
4519
.
(5) Smeu, M.; DiLabio, G. A. J. Org. Chem. 2007, 72, 4520–4523
.
10.1021/ol900635z CCC: $40.75
Published on Web 04/27/2009
 2009 American Chemical Society

unimolecular reaction (Scheme 2, path a),6,7 and the failure
to observe the O-neophyl rearrangement (path b) reasonably
reflects the lower stability of the 2-phenoxy-2-propyl radical
as compared to the 1-phenoxy-1-phenylalkyl one displayed
in Scheme 1. In this context, we felt that by introducing an
appropriate reporter group on the aromatic ring, the bridged
radical derived from ring closure in the cumyloxyl radical
may undergo a sufficiently fast rearrangement able to divert
it from the equilibrium shown in Scheme 2. This evidence
would support the hypothesis that cumyloxyl (and, more
generally, arylcarbinyloxyl) radicals exist in equilibrium with
1-oxaspiro[2,5]octadienyl radicals. A suitable candidate for
this purpose appears to be a para cyclopropyl substituent as
it is known that the cyclopropylcarbinyl radical undergoes
ring-opening to the 3-butenyl radical with k ) 6.7 × 107
s-1 (eq 1).8
of the 2-(4-cyclopropylphenyl)-2-propoxyl (1•), 2-(4-(2,2-
diphenylcyclopropyl)phenyl)-2-propoxyl (2•), and 2-(4-(2,2-
diphenylcyclopropyl)phenyl)-2-butoxyl (3•) radicals whose
structures are shown in Figure 1.
Figure 1.
Structures of alkoxyl radicals 1•-3•.
1• has been generated in MeCN by 266 nm laser flash
photolysis (LFP) of the parent peroxide 1p (eq 3).
However, as compared to the cyclopropylcarbinyl radical,
the bridged radical derived from p-cyclopropylcumyloxyl
(if formed) would be strongly stabilized by the cyclohexa-
dienyl system, and a significantly lower rate constant for ring-
opening can be expected. The 2,2-diphenylcyclopropyl group
seems a better choice, because the rate constant for the 2,2-
diphenylcyclopropylcarbinyl f 1,1-diphenyl-3-butenyl radi-
cal rearrangement has been determined as k ) 5 × 1011 s-1
(eq 2).9
Figure 2 displays the time-resolved absorption spectra
observed after LFP of an Ar-saturated MeCN solution
containing 1p, showing after 160 ns (filled circles) a spectrum
characterized by two bands centered at 320 and 540 nm, that,
in full agreement with the spectra of ring-substituted cumy-
loxyl radicals,6,15,16 is assigned to 1•.
In addition, the rearranged 1,1-diphenylalkenyl radical is
characterized by an absorption band centered at 335 nm,10-12
a feature that makes the study of these processes possible
by time-resolved absorption spectroscopy.
Phenyl-substituted cyclopropyl groups have been exten-
sively applied as reporter groups for the study of a variety
of radical reactions,10-14 however, to our knowledge, their
application to the study of cyclohexadienyl radicals is
unprecedented.
In order to obtain information on the role of phenyl
bridging in arylcarbinyloxyl radicals, we have carried out
product and time-resolved kinetic studies on the reactivity
(6) Baciocchi, E.; Bietti, M.; Salamone, M.; Steenken, S. J. Org. Chem.
2002, 67, 2266–2270.
(7) Avila, D. V.; Brown, C. E.; Ingold, K. U.; Lusztyk, J. J. Am. Chem.
Soc. 1993, 115, 466–470.
(8) Halgren, T. A.; Roberts, J. D.; Horner, J. H.; Martinez, F. N.;
Tronche, C.; Newcomb, M. J. Am. Chem. Soc. 2000, 122, 2988–2994.
(9) Newcomb, M.; Johnson, C. C.; Manek, M. B.; Varick, T. R. J. Am.
Chem. Soc. 1992, 114, 10915–10921.
Figure 2. Time-resolved spectra observed after 266 nm LFP of 1p
(2.0 mM) in an Ar-saturated MeCN solution (T ) 25 °C) at 160 ns
(filled circles), 416 ns (empty circles), 1.2 µs (filled squares), 2.4
µs (empty squares), and 7.0 µs (diamonds), after the 8 ns, 10 mJ
pulse. Insets: (a) first-order buildup at 285 nm; (b) first-order decay
at 320 nm; (c) first-order decay at 540 nm.
(10) DeZutter, C. B.; Horner, J. H.; Newcomb, M. J. Phys. Chem. A
2008, 112, 1891–1896
(11) Newcomb, M.; Daublain, P.; Horner, J. H. J. Org. Chem. 2002,
67, 8669–8671
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(12) Horner, J. H.; Choi, S.-Y.; Newcomb, M. Org. Lett. 2000, 2, 3369–
3372
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(13) Newcomb, M.; Toy, P. H. Acc. Chem. Res. 2000, 33, 449–455
(14) Newcomb, M.; Tanaka, N.; Bouvier, A.; Tronche, C.; Horner, J. H.;
.
The observation of a band centered at 540 nm is in full
agreement with the electron-donating character of the cy-
Musa, O. M.; Martinez, F. N. J. Am. Chem. Soc. 1996, 118, 8505–8506
.
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Org. Lett., Vol. 11, No. 11, 2009

clopropyl substituent, as it is known that the position of the
cumyloxyl radical visible absorption band, centered at 485
nm, is red-shifted by electron releasing ring-substitu-
ents.6,15,16 1• undergoes a first-order decay (insets b and c:
kV ) 8.0 × 105 s-1) accompanied by a corresponding buildup
at 285 nm (inset a: kv ) 8.0 × 105 s-1) that, in line with
previous studies on cumyloxyl radicals,6,17,18 is assigned to
4-cyclopropylacetophenone (4) (an isosbestic point is visible
at 305 nm), formed after C-CH3 ꢀ-scission in 1•. Quite
importantly, the rate constant measured for ꢀ-scission of 1•
(kꢀ) is in line with those measured previously in MeCN for
a series of ring-substituted cumyloxyl radicals (kꢀ ) 0.7-1.0
× 106 s-1),6 confirming that ꢀ-scission is not significantly
influenced by ring substitution. As expected, the 540, 320,
and 285 nm bands were not affected by the presence of
oxygen.
4,7-diene (5b), 4-(2-hydroxy-2-butyl)benzencarbaldehyde
(6b), and 4-(2,2-diphenylcyclopropyl)acetophenone (7) in
57%, 20%, and 23% yield, respectively (Scheme 4).
Scheme 4
With peroxides 2p and 3p, a very strong emission was
observed in the region below 400 nm following 266 nm LFP
(see Figures S2 and S3, Supporting Information) and no
evidence for the formation of radicals 2• and 3• was obtained.
An analogous behavior was observed after 266 nm LFP of
the corresponding arylalkanols 2a and 3a (see Figure S4,
Supporting Information). With all these systems, the presence
of the diphenylcyclopropyl group leads to a strong emission
in the region below 400 nm. Unfortunately, the emission
observed with 2p and 3p does not allow clear evidence for
the formation of a species absorbing at 335 nm, indicative
of a 2,2-diphenylcyclopropylcarbinyl f 1,1-diphenyl-3-
butenyl type radical rearrangement, to be obtained (see the
Supporting Information).
Product Studies. Arylcarbinyloxyl radicals 1•-3• have
been generated photochemically by visible light irradiation
of CH2Cl2 solutions containing the parent arylalkanols
(1a-3a), (diacetoxy)iodobenzene (DIB), and I2. It is well
established that under these conditions the DIB/I2 reagent
converts alcohols into hypoiodites that are then photolyzed
to give alkoxyl radicals, precursors of the observed reaction
products (Scheme 3).2,19,20
Products 5a and 5b have been isolated and unambiguously
characterized by 1H NMR, 13C NMR, and correlation NMR
(see the Supporting Information). Aldehydes 6a and 6b have
been identified by comparison with authentic samples (see
the Supporting Information). It is, however, important to
point out that when the reaction mixtures obtained after
irradiation of substrates 2a and 3a in the presence of DIB
and I2 were analyzed by 1H NMR prior to workup, no trace
of aldehydes 6a and 6b was detected, clearly indicating that
these products are formed during workup and are not primary
products deriving from the reactions of the intermediate
alkoxyl radicals 2• and 3•.21
The results obtained in the product and time-resolved
studies can be rationalized on the basis of the mechanisms
shown in Scheme 5. Irradiation of 1a led to the formation
of 4-cyclopropylacetophenone (4), indicating that under these
conditions the intermediate cumyloxyl radical 1• undergoes
exclusive ꢀ-scission (Scheme 5, path a, R ) H), in full
agreement with the results of the LFP experiments described
above. Of course, in this case, no information on the
existence of an equilibrium between 1• and the bridged
cyclopropylcarbinyl radical (path b) could be obtained. If
formed, the latter radical would strongly benefit from the
stabilization imposed by the cyclohexadienyl system, and
accordingly, in 1• cyclopropyl ring-opening (path c) is not
expected to compete to any significant extent with ꢀ-scission.
Scheme 3
(15) Avila, D. V.; Ingold, K. U.; Di Nardo, A. A.; Zerbetto, F.; Zgierski,
M. Z.; Lusztyk, J. J. Am. Chem. Soc. 1995, 117, 2711–2718.
(16) Avila, D. V.; Lusztyk, J.; Ingold, K. U. J. Am. Chem. Soc. 1992,
114, 6576–6577.
(17) Bietti, M.; Gente, G.; Salamone, M. J. Org. Chem. 2005, 70, 6820–
6826.
(18) Banks, J. T.; Scaiano, J. C. J. Am. Chem. Soc. 1993, 115, 6409–
6413.
(19) Sua´rez, E.; Rodriguez, M. S. In Radicals in Organic Synthesis;
Renaud, P., Sibi, M. P., Eds.; Wiley-VCH: Weinheim, 2001; Vol. 2, pp
440-454.
Under these conditions, reaction of 1a led to the exclusive
formation of 4-cyclopropylacetophenone (4).
Reaction of 2a led to the formation of 2,2-dimethyl-6-(3-
hydroxy-3,3-diphenylpropyliden)-1-oxaspiro[2,5]octa-4,7-di-
ene (5a) and 4-(2-hydroxy-2-propyl)benzencarbaldehyde (6a)
in 67% and 33% yield, respectively (Scheme 4).
(20) Courtneidge, J. L.; Lusztyk, J.; Page`, D. Tetrahedron Lett. 1994,
35, 1003–1006.
(21) The 1H NMR spectrum obtained after irradiation of 3a in the
presence of DIB and I2 in CD2Cl2, registered prior to workup (see the
Supporting Information), showed the formation of 5b and 7 in 76% and
24% yield, respectively. The observation that the amount of 5b obtained in
this experiment is equal, within experimental error, to the sum of 5b and
6b obtained after workup (77%, see Scheme 4) clearly indicates that 6b
derives from the decomposition of the first formed 5b.
Reaction of 3a led to the formation of 2-ethyl-2-methyl-
6-(3-hydroxy-3,3-diphenylpropyliden)-1-oxaspiro[2,5]octa-
Org. Lett., Vol. 11, No. 11, 2009
2455

Scheme 5
With 2a, irradiation led to the exclusive formation of 5a.22
In conclusion, by means of detailed product and time-
resolved studies, convincing experimental evidence in sup-
port of the existence of an equilibrium between cumyloxyl
and 1-oxaspiro[2,5]octadienyl radicals has been provided.
A consequence of this observation is the reopening of the
debate on the nature of the visible absorption band of
arylcarbinyloxyl radicals.5,6,15-17,26,27 Given the existence
of this equilibrium, and taking into account that the
spiro[2,5]octadienyl radical (and, more generally, cyclohexa-
dienyl radicals) is characterized by a broad absorption band
in the visible region,28 it is not possible to exclude that the
UV and visible absorptions previously assigned to arylcarbi-
nyloxyl radicals effectively arise from two species in rapid
equilibrium.15,27 Further work in our laboratory will probe
this issue.
The formation of this product can be rationalized in terms
of cyclopropyl ring opening in the intermediate bridged
radical (Scheme 5, pathways c-e, R ) Ph; R1 ) Me),23
supporting the hypothesis that this radical exists in equilib-
rium with 2•. The failure to observe 7, deriving from
ꢀ-scission in 2•, clearly indicates that in the presence of two
phenyl substituents on the cyclopropyl group, ring-opening
occurs significantly faster than C-Me ꢀ-scission. By con-
sidering that in ring-substituted cumyloxyl radicals kꢀ is not
significantly influenced by the nature of the substituent,6 it
is reasonable to assume the same rate constant for ꢀ-scission
in 2• and 1• (kꢀ ) 8.0 × 105 s-1). Along this line, and
considering the results of product studies described above,
it is possible to place a lower limit to the rate constant for
cyclopropyl ring-opening in the bridged radical in equilib-
rium with 2• as k g 108 s-1.
Acknowledgment. Financial support from MIUR is
acknowledged. We thank Lorenzo Stella (Universita` “Tor
Vergata) for the use of LFP equipment, Daniel O. Cicero
(Universita` “Tor Vergata”) for assistance in the NMR
experiments, and Chryssostomos Chatgilialoglu (ISOF -
CNR, Italy) for helpful discussions.
With 3a, irradiation led to the formation of 5b and 7, in
a 3:1 ratio.21 Compound 5b derives from cyclopropyl ring-
opening in the intermediate bridged radical (Scheme 5,
pathways c-e, R ) Ph; R1 ) Et), whereas 7 is formed
following C-Et fragmentation in 3• (path a, R ) Ph).
By assuming, in analogy with the discussion outlined
above for 2•, that C-Et ꢀ-scission in 3• occurs with the same
rate constant as that measured previously for C-Et ꢀ-scission
in the 2-(4-methylphenyl)-2-butoxyl radical (kꢀ ) 2.5 × 108
s-1),25 and taking into account the product distribution
observed for 3•, a rate constant k ≈ 7.5 × 108 s-1 can be
estimated for cyclopropyl ring-opening in the bridged radical
in equilibrium with 3•.
Supporting Information Available: Details on product
studies, synthesis, and characterization of arylalkanols
1a-3a, peroxides 1p-3p, and products 4-7. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL900635Z
(22) Considering that, as mentioned above, aldehyde (6a) derives from
the decomposition of 5a during workup.
(25) Bietti, M.; Lanzalunga, O.; Salamone, M. J. Org. Chem. 2005, 70,
(23) When the DIB/I2 system is used, carbon radicals rapidly react with
I2 to give the corresponding alkyl iodides (see refs 20 and 24); it is thus
reasonable to propose that 5a is formed during workup following solvolysis
of the tertiary iodide (Scheme 5, path e, R ) Ph; R1 ) Me).
(24) Aureliano Antunes, C. S.; Bietti, M.; Lanzalunga, O.; Salamone,
M. J. Org. Chem. 2004, 69, 5281–5289.
1417–1422.
(26) Banks, J. T.; Scaiano, J. C. J. Phys. Chem. 1995, 99, 3527–3531
.
(27) Falvey, D. E.; Khambatta, B. S.; Schuster, G. B. J. Phys. Chem.
1990, 94, 1056–1059
.
(28) Effio, A.; Ingold, K. U.; Griller, D.; Scaiano, J. C.; Sheng, S. J.
J. Am. Chem. Soc. 1980, 102, 6063–6068.
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