The O-neophyl rearrangement of 1,1-diarylalkoxyl radicals. Experimental evidence for the formation of an intermediate 1-oxaspiro[2,5]octadienyl radical

Article abstract of DOI:10.1016/j.tetlet.2010.05.149

A product study on the reactivity of a 1,1-diarylalkoxyl radical bearing 2,2-diphenylcyclopropyl groups in the para-positions has been carried out. The exclusive formation of a product deriving from cyclopropyl ring-opening has been observed, indicating t

Full text of DOI:10.1016/j.tetlet.2010.05.149

Tetrahedron Letters 51 (2010) 4129–4131
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The O-neophyl rearrangement of 1,1-diarylalkoxyl radicals. Experimental
evidence for the formation of an intermediate 1-oxaspiro[2,5]octadienyl radical
*
Massimo Bietti , Alessandra Calcagni, Daniel Oscar Cicero, Roberto Martella, Michela Salamone
Dipartimento di Scienze e Tecnologie Chimiche, Università ‘Tor Vergata’, Via della Ricerca Scientifica, 1 I-00133 Rome, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
A product study on the reactivity of a 1,1-diarylalkoxyl radical bearing 2,2-diphenylcyclopropyl groups in
the para-positions has been carried out. The exclusive formation of a product deriving from cyclopropyl
ring-opening has been observed, indicating that 1,1-diarylalkoxyl radicals exist in equilibrium with a
bridged 1-oxaspiro[2,5]octadienyl radical. This represents the first experimental evidence in support of
the stepwise nature of the O-neophyl rearrangement of 1,1-diarylalkoxyl radicals.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 6 May 2010
Accepted 28 May 2010
Available online 4 June 2010
Keywords:
Alkoxyl radical
O-Neophyl rearrangement
Cyclopropylcarbinyl radical
Ring-opening
Alkoxyl radicals represent an important class of highly reactive
oxygen-centered radicals. These species play a key role in several
chemical and biological processes, such as the photooxidation of
hydrocarbons in the atmosphere,1 lipid peroxidation,2 and the
anti-malarial action of natural endoperoxides,3 and are involved
moreover in a variety of synthetically useful procedures.4 The
uni- and bimolecular reactions of alkoxyl radicals have been thor-
oughly investigated. Relevant examples of the former processes in-
clude intramolecular hydrogen atom transfer5 and C–C bond
fragmentation reactions (b-scission,6 and O-neophyl rearrange-
ment7). Typical bimolecular processes are represented by hydro-
gen atom abstraction reactions8 and by addition reactions to C@C
double bonds,9 organophosphorus,10,11 and organoboron
compounds.11
1-oxaspiro[2,5]octadienyl radical structure representing, respec-
tively, a transition state or a discrete intermediate along the
reaction pathway. Only recently, however, computational studies
have provided convincing support to the hypothesis that the
O-neophyl rearrangement of 1,1-diarylalkoxyl radicals proceeds
through the reversible formation of an intermediate 1-oxaspi-
ro[2,5]octadienyl radical as described in Scheme 1.17,18
No conclusive experimental evidence in support of this hypoth-
esis is instead available. In this context, it is, however, important to
point out that a recent product and time-resolved kinetic study
carried out by some of us has clearly shown that the para-(2,2-
diphenylcyclopropyl)cumyloxyl radical (1ꢀ) exists in equilibrium
with a 2,2-dimethyl-1-oxaspiro[2,5]octadienyl radical (2ꢀ).19
Cumyloxyl radicals are known to undergo C–CH3 b-scission as
the exclusive unimolecular reaction (Scheme 2, path a),6f,6g,20,21
and the failure to observe the O-neophyl rearrangement (Scheme
2, path b) reasonably reflects the lower stability of the 2-phen-
oxy-2-propyl radical as compared to the 1-phenoxy-1-phenylalkyl
one displayed in Scheme 1.
The O-neophyl rearrangement of alkoxyl radicals, first de-
scribed by Wieland in 1911,12 has received since then considerable
attention. This process converts an oxygen-centered radical into a
significantly more stable (benzylic) carbon-centered radical
through a 1,2-aryl shift, and has been observed for radicals that
bear at least two aryl groups in the
a
-position (Eq. (1)).
Along this line, by introducing a 2,2-diphenylcyclopropyl repor-
ter group in the para-position, the exclusive formation of product A
(Scheme 3) has been observed.19
O
C
R
Ar
O
C
R
Ar
Ar
Ar
A result that has been interpreted in terms of the existence of an
equilibrium between 1ꢀ and 2ꢀ followed by a fast 2,2-diphenylcy-
clopropylcarbinyl?1,1-diphenyl-3-butenyl radical rearrangement
in the latter radical. The failure to observe para-(2,2-diphenylcyclo-
propyl) acetophenone (B) deriving from C–CH3 b-scission in 1ꢀ
clearly indicates that in the presence of two phenyl substituents
on the cyclopropyl group, this process does not compete with
cyclopropyl ring-opening in 2ꢀ.22
ð1Þ
R = H, Me, cPr, Ar
A strongly debated question has been whether this rearrange-
ment is a concerted or a stepwise process,13–16 with a bridged
* Corresponding author. Tel.: +39 0672594384; fax: +39 0672594328.
E-mail address: bietti@uniroma2.it (M. Bietti).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.05.149

4130
M. Bietti et al. / Tetrahedron Letters 51 (2010) 4129–4131
O
C
R
O
C
R
O
C
R
k1
k2
k-1
R = Me, cPr
Scheme 1.
2-propanol in the presence of DIB and I2 as described above
(Scheme 3).19
O
C
O
CH3
CH3
CH3
O
CH3
H3C C CH3
O C
The formation of C can be rationalized in terms of cyclopropyl
ring-opening in the intermediate-bridged radical 4ꢀ (Scheme 5,
pathways b–d, Ar = 4-(2,2-diphenylcyclopropyl)phenyl),27 in line
with the hypothesis of the existence of an equilibrium between
this radical and 3ꢀ. This finding clearly represents the first experi-
mental evidence for the formation of an intermediate-bridged 1-
oxaspiro[2,5]octadienyl radical in the reactions of 1,1-diarylalkoxyl
radicals, in full agreement with the computational results dis-
cussed above.17,18
CH3
- CH3
a
b
X
X
X
X
Scheme 2.
On the basis of these results, it seemed particularly interesting
to extend the approach described above for the cumyloxyl radical
also to 1,1-diarylalkoxyl radicals, in order to establish if a bridged
1-oxaspiro[2,5]octadienyl radical is actually an intermediate in the
O-neophyl rearrangement, and moreover, if the existence of this
equilibrium is a general feature of arylcarbinyloxyl radicals. For
this purpose, we have synthesized cyclopropyl[bis(4-(2,2-diphe-
nylcyclopropyl)phenyl)]methanol (3), precursor of the 1,1-diary-
lalkoxyl radical 3ꢀ, whose structure is displayed below.24 3ꢀ has
been generated photochemically by visible light irradiation of
CH2Cl2 solutions containing 3, (diacetoxy)iodobenzene (DIB), and
I2. It is well established that under these conditions the DIB/I2 re-
agent converts alcohols (ROH) into hypoiodites (ROI) that are then
photolyzed to give alkoxyl radicals (ROꢀ), precursors of the ob-
served reaction products.14b,25,26
Under these conditions the reaction of 3 led to the exclusive
formation of 2-cyclopropyl-2-(4-(2,2-diphenylcyclopropyl)phenyl)-
6-(3-hydroxy-3,3-diphenylpropyliden)-1-oxaspiro[2,5]octa-4,7-
diene (C) (Scheme 4).
Product C has been isolated by preparative TLC and unambigu-
ously characterized by 1H NMR, 13C NMR, and correlation NMR (see
Supplementary data). In addition, the spectroscopic data are in
excellent agreement with those obtained previously for the struc-
turally related product 2,2-dimethyl-6-(3-hydroxy-3,3-diphenyl-
propyliden)-1-oxaspiro[2,5]octa-4,7-diene (A), obtained after
visible light irradiation of 2-(4-(2,2-diphenylcyclopropyl)phenyl)-
O
C Ar
O
O
O
O
Ar
Ar
Ar
Ar
a
b
c
d
H2O
I2
Ph
Ph
Ph
Ph
Ph
Ph
I
Ph
OH
Ph
Ph
4
3
Ph
C
e
O
C
Ar
O C
I
Ar
O
C
g
f
Ar
I2
D
Ph
Ph
Ph
Ph
Scheme 5.
O
O
CH3
CH3
CH3
CH3
CH3
CH3
H3C C CH3
C CH3
O
O
O
CH3
Ph
Ph
Ph
Ph
Ph
Ph
1
2
B
A
Ph
Ph
OH
Ph
Ph
Scheme 3.
DIB / I2
hν (480 nm)
OH
O
Ph
Ph
Ph
Ph
CH2Cl2, Ar
Ph
OH
Ph
Ph
Ph
3
C
Scheme 4.

M. Bietti et al. / Tetrahedron Letters 51 (2010) 4129–4131
4131
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in 3ꢀ (cyclopropyl 4-(2,2-diphenylcyclopropyl)phenyl ketone (D))
indicates that in the presence of two phenyl substituents on the
cyclopropyl group, 4ꢀ undergoes cyclopropyl ring-opening (path
b) significantly faster than the opening of the oxirane ring (path
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62.4 ꢁ 106 sꢂ1 14b
,
and a similar (or lower) value can be reasonably
predicted also for 3ꢀ.
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diarylalkoxyl radical 3ꢀ and an 1-oxaspiro[2,5]octadienyl radical
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ture of arylcarbinyloxyl radicals, strongly supporting the
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Acknowledgment
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Financial support from the Ministero dell’Istruzione dell’Uni-
versità e della Ricerca (MIUR) is gratefully acknowledged.
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Supplementary data
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Supplementary data (details on product studies, synthesis of
substrate 3 and characterization of product C) associated with this
article can be found, in the online version, at doi:10.1016/
j.tetlet.2010.05.149.
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References and notes
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.
A
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radicals.6g,20,21
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reasonable to propose that also in this case
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ˇ
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following solvolysis of the tertiary iodide (Scheme 5, path d).
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