Radical additions of acyclic and cyclic ethers to alkenes via an allyl transfer reaction involving phthalimido-N-oxyl radical

Article abstract of DOI:10.1016/j.tet.2016.05.046

Direct functionalization of rudimentary and cheap starting materials to yield complex value added products is of great interest to synthetic chemists. Particularly, direct functionalization of cheap commodity molecules that have been traditionally considered inert to known reactions are of widespread interest. We have previously demonstrated the functionalization of benzylic C–H bonds via an allyl transfer reaction using various allyl-phthalimido-N-oxyl substrates. In this work, we demonstrate the extension of our mild, metal-free, and neutral allyl transfer methodology to the direct functionalization of ethers. The C–H bond in α position to the ether oxygen in various acyclic and cyclic ethers was functionalized in high yields demonstrating wide substrate scope for this transformation. Furthermore, selective mono-functionalization of symmetrical cyclic ethers and regioselective functionalization of unsymmetrical ethers was achieved, thus demonstrating further utility of this reaction. Finally, kinetic chain length measurements were performed, which provided valuable insights into the initial rates and efficiency of the chain process involving the phthalimido-N-oxyl (PINO[rad]) radical.

Full text of DOI:10.1016/j.tet.2016.05.046

Tetrahedron xxx (2016) 1e10
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Radical additions of acyclic and cyclic ethers to alkenes via an allyl
transfer reaction involving phthalimido-N-oxyl radical
Shradha V. Patil, James M. Tanko *
Virginia Polytechnic Institute and State University, Department of Chemistry, Blacksburg, 24061, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Direct functionalization of rudimentary and cheap starting materials to yield complex value added
products is of great interest to synthetic chemists. Particularly, direct functionalization of cheap com-
modity molecules that have been traditionally considered inert to known reactions are of widespread
interest. We have previously demonstrated the functionalization of benzylic CeH bonds via an allyl
transfer reaction using various allyl-phthalimido-N-oxyl substrates. In this work, we demonstrate the
extension of our mild, metal-free, and neutral allyl transfer methodology to the direct functionalization
Received 28 March 2016
Received in revised form 13 May 2016
Accepted 16 May 2016
Available online xxx
Keywords:
of ethers. The CeH bond in
a position to the ether oxygen in various acyclic and cyclic ethers was
Ether functionalization
Phthalimido-N-oxyl radicals
Chain reaction
Allyl transfer
CeH bond
functionalized in high yields demonstrating wide substrate scope for this transformation. Furthermore,
selective mono-functionalization of symmetrical cyclic ethers and regioselective functionalization of
unsymmetrical ethers was achieved, thus demonstrating further utility of this reaction. Finally, kinetic
chain length measurements were performed, which provided valuable insights into the initial rates and
ꢀ
efficiency of the chain process involving the phthalimido-N-oxyl (PINO ) radical.
Ó 2016 Elsevier Ltd. All rights reserved.
1
. Introduction
alkenylation of THF with 1,2-disubstituted vinyl triflones leading
6
c
to
synthesize
thalimide)/Co(OAc)
kenes, radical addition of alcohols to the alkynes using TBHP (tri-
butyl hydroperoxide) to yield corresponding allylic alcohols, and
a
-vinyl products, reactions of THF with polyfluoro-alkenes to
-polyfluoroalkyl ethers, NHPI (N-hydroxyph-
catalyzed radical addition of ethers to al-
The direct CeH bond activation and functionalization reactions
are fascinating to organic chemists, as they provide easily accessi-
ble, economical, and novel routes for interesting synthetic appli-
cations. Various high efficiency and versatile methods have been
reported for such activations and functionalization reactions.
These reactions can be categorized mainly into: 1) sp
a
2
7
8
1
3 2 2 2
finally, radical additions using initiator BEt /O or Me Zn/O lead-
2
9
a
-CeH re-
-CeH reactions
ing to the formation of hydroxy alkyl ethers.
2
3
actions of arene, alkene, aldehyde, imine; 2) sp
a
In earlier studies, we devised a free radical-based chain reaction
3
3
of allyl, benzyl, carbonyl compounds; 3) sp
heteroatomic compounds containing oxygen, nitrogen and sulfur.
The third type, sp3
-CeH activation followed by CeC bond for-
mation in reactions of alcohols, ethers, and amines is quite useful
because of the direct conversion of these relatively inert com-
a
-CeH reactions of
that achieves hydrocarbon functionalization and CeC bond for-
4
10
mation that achieves the overall conversion R-HþCH
2
]C(Z)
þH-X (where X¼Br or more recently, the N-
hydroxyphthalimide radical, abbreviated as PINO). The mechanism
a
2 2 2
CH X/RCH C(Z)]CH
1
0c
for this reaction is depicted in Scheme 1.
In developing this
pounds into substrates of varying complexity. This article summa-
process, several known radical reactions (hydrogen atom abstrac-
tion, radical additions to unsaturated centers, and b-cleavage)
3
11
rizes our successful efforts in developing a method of sp
a
-CeH
activation and ether functionalization via an allyl transfer reaction.
The addition-elimination reactions of carbon-centered radicals
were tailored to achieve the desired overall conversion. Initially,
the substrates were limited to allyl bromides (where bromine atom
was the chain carrier) and benzylic hydrocarbons (e.g., toluene,
ethyl benzene, cumene, owing to their weak CeH bond, BDE
88e92 kcal). More recently, we were able to replace the Br with
PINO, which produces the by-product N-hydroxyphthalimide
generated from ethers via
been extensively studied, particularly for cyclic ethers.
ples include radical addition-elimination reaction of THF with
a-CeH activation-functionalization have
2b,5
Exam-
12
6
alkenyl or alkynyl triflones leading to
a-acetylenic ethers,
(NHPI). Quite conveniently, NHPI precipitates out of solution
eliminating the need for an HBr scavenger, and making the work-up
10a,10c
*
Corresponding author. Tel.: þ1 540 231 6687; fax: þ1 540 231 3255; e-mail
particularly easy and convenient).
address: jtanko@vt.edu (J.M. Tanko).
http://dx.doi.org/10.1016/j.tet.2016.05.046
0
040-4020/Ó 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Patil, S. V.; Tanko, J. M., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.05.046

2
S.V. Patil, J.M. Tanko / Tetrahedron xxx (2016) 1e10
8, respectively in high (up to 90%) yields (see Supplementary data
S2 and S6 for characterization).
Table 1
Functionalization of acyclic ethers via allyl transfer reaction
Entrya Ether
Zb
Time (h) Product Isolated yield (%) GC yield (%)
1
2
3
CO
Ph
CO
Ph
2
Et
Et
4
24
4
5
6
7
8
83
85
85
85
90
90
90
90
2
Scheme 1. Allyl transfer reaction for hydrocarbon functionalization.
4
24
Since the bond dissociation energies of ethers and acetals are
a
DTBPO¼0.07 M, ether as solvent.
Allyl-PINO substrate¼0.45 M.
comparable to benzylic hydrocarbons, we reckoned that this allyl
transfer chemistry could be adapted to a new class of substrates.
Moreover, because acetals are essentially protected aldehydes, it
was thought that we could further develop this allyl transfer
chemistry using acetals as acyl radical equivalents.
b
2
.3. Direct functionalization of cyclic ethers
In conjunction with our work on acyclic ethers, we speculated
that the same functionalization would be possible with cyclic
ethers and thioethers. Cyclic ethers such as tetrahydrofuran (THF),
2
2
. Results and discussion
2
-MeTHF are key structural motifs in a large number of biologically
.1. Introduction to ether functionalization via allyl transfer
14
active compounds and natural products. Thus, direct functional-
ization of these substrates using allyl transfer chemistry would
-CeH bonds13
a
Similar to benzylic hydrocarbons, ethers have weak
15
provide the basis for a new and useful synthetic method. We
screened a set of ethers such as THF, THP (tetrahydropyran), 1,4-
dioxane, THT (tetrahydrothiophene) and 1,3-benzodioxole in the
allyl transfer reaction with substrates 3 and 4. The conditions for
these reactions are similar to those described above. And, as was
the case for the acyclic ethers, these compounds have only one
functionalizable CeH bond owing to its symmetry. The observed
products for these reactions are shown in Fig. 2 (see Supplementary
data S2 for spectral data).
(
THF, BDE 93.8 kcal/mol; 1,3-dioxane, BDE 93.3 kcal/mol) owing to the
resonance stabilization of resulting radical 2 by the vicinal oxygen
atom (Fig. 1). Ethers are thus a suitable choice as substrates for H-ab-
straction, and in this paper, we comprehensively discuss the method of
a
-alkoxyl CeH bond functionalization via allyl transfer using phthali-
ꢀ
mido-N-oxyl radical (PINO ). As hoped, the reaction proceeds via the
abstraction of
elimination of the carbon radical to allyl-PINO substrates (Scheme 1).
a-hydrogen from ether, with the subsequent addition/
Fig. 1. Resonance stabilization of a-alkoxyl radical derived from tetrahydrofuran (THF).
2
.2. Direct functionalization of acyclic ethers via allyl transfer
The reactions of acyclic ethers (diethyl ether and tert-butyl ethyl
ꢁ
ether) with allyl-PINO substrates 3 and 4 were performed at 120 C
in sealed pressure tubes (Scheme 2). The precipitation of the side
product, NHPI, as a white solid helped recycle it making this a cost
effective synthetic method. The data in Table 1 reports the isolated
and GC yields of these reactions, and shows that the reactions of
diethyl ether and tert-butyl ethyl ether (both of which possess
equivalent reactive hydrogen atoms) led to products 5, 6, and 7, and
Fig. 2. Products arising from reactions of cyclic ethers and thioether with ally-PINO
substrates 3 and 4.
Scheme 2. Functionalization of acyclic ethers; ethyl ether and tert-butyl ethyl ether via allyl transfer reactions (DTBPO¼di-tert-butyl peroxide).
Please cite this article in press as: Patil, S. V.; Tanko, J. M., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.05.046

S.V. Patil, J.M. Tanko / Tetrahedron xxx (2016) 1e10
3
Table 2 reports the results of cyclic ether and thioether func-
tionalization. In the case of THF (entries 1, 2), the observed yield
was slightly lower than the other ethers possibly due to further
addition of reactive THF radical to the product alkene especially
when Z¼CO
2
Et. Although this phenomenon was not prominently
observed in other cases, trace impurities analysis using MS con-
firmed this further addition. High isolated yields were observed for
reactions of THP and 1,4-dioxane (entries 3e6). THT (entries 7, 8)
could also be easily functionalized using this method. Similarly, the
1,3-benzodioxole (entries 9,10), which is an important building
Scheme 3. Competition for H abstraction in A) 2-MeTHF, B) 1,3-dioxane.
block for biologically active heterocycles, was also functionalized
using this method.
Table 2
a
Functionalization of cyclic ethers and benzo-1,3-dioxole via allyl transfer reaction
Scheme 4. Functionalization of 2-MeTHF via allyl transfer reaction.
Entry Ether
Z
Time (h) Product Isolated yield (%) GC yield (%)
2.5. Functionalization of 2-MeTHF via allyl transfer reaction
1
2
3
4
5
6
7
8
9
CO
Ph
CO
Ph
CO
Ph
CO
Ph
CO
Ph
2
2
2
2
2
Et
Et
Et
Et
Et
1
16
2
9
60
75
85
84
88
85
85
85
80
75
65(ꢂ3)
70(ꢂ2)
85(ꢂ3)
90(ꢂ2)
88(ꢂ2)
90(ꢂ1)
88(ꢂ1)
90(ꢂ2)
86(ꢂ3)
81(ꢂ2)
Table 3 reports the results of the reaction of 2-MeTHF with allyl-
PINOs 3 and 4. For the reaction in entry 1, Gas chromatographic
analysis was conducted to calculate the relative ratios of 28 to 26
and 25 to 27 shown in Fig. 2. Analysis by GC revealed three products
were formed in this reaction. The major product is (80%) is 26,
whereas the minor products are cis- and trans-28 formed in 20%
10
11
12
13
14
15
16
17
18
1
yield. These assignments were confirmed using H NMR analysis in
16
1
which methyl protons from the major product appear as a singlet at
.12, whereas methyl protons from the cis and trans isomers of 28
appear as doublets at 1.20 and 1.25 (see Supplementary data, Fig. S9
and S10) (see Fig. 3).
1
18
2
Table 3
Functionalization of 2-MeTHF via allyl transfer reaction
Entry Substrate Time (h) Overall Product
yield (%)
GC yield (%) Integrated
NMR yield (%)
79
18
8
1a
3
36
80
26
8(cisþtrans) 20
25
7(cisþtrans)
80
2
21
70
30
2a
4
12
82
d
2
10
14
a
Reactions were performed in sealed pressure tubes using neat 2-MeTHF and di-
a
Sealed tube, 120 ꢁC, 3, 4¼0.45 M, DTBPO¼0.007 M, ether as solvent).
tert-butyl peroxide (15 mol %), (Sealed tube, 120
MeTHF¼10.0 M).
ꢁ
C) (3, 4¼0.4 M, DTBPO¼0.06 M, 2-
(
2
.4. Competition for H-abstraction in 2-MeTHF and 1,3-
dioxane
Cyclic ethers such as 2-MeTHF and 1,3-dioxane, which are un-
symmetrical and thus have more than one functionalizable -hy-
a
drogen atoms, were also studied. In these cases, we feared that the
allyl transfer reaction might lead to multiple products, owing to the
competition in hydrogen abstraction.
For example, in the case of 2-MeTHF 19, abstraction of H
a
leads
to a tertiary radical 20, whereas abstraction of H leads to a sec-
b
ondary radical 21. Thus, we expected reasonably good chemo-
selectivity for reactions of 2-MeTHF since 20 is expected to be more
stable than 21. In case of 1,3-dioxane 22, both hydrogens (H
) are secondary leading to radicals 23 and 24, and thus, lower
chemoselectivity was anticipated (see Schemes 3 and 4).
c
and
H
d
Fig. 3. GC analysis of 2-MeTHF functionalization showing all regioisomeric products.
Please cite this article in press as: Patil, S. V.; Tanko, J. M., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.05.046

4
S.V. Patil, J.M. Tanko / Tetrahedron xxx (2016) 1e10
2
.6. Functionalization of 1,3-dioxane via allyl transfer
does not adversely impact the overall yield until there are less than
reaction
3 equiv of THF present. These results demonstrate that these re-
actions can be performed using considerably lower concentrations
of substrate.
As mentioned above, similar to 2-MeTHF, 1,3-dioxane also has
multiple functionalizable CeH bonds. The functionalization of 1,3-
dioxane was performed using di-tert-butyl peroxide (15 mol %) in
neat 1,3-dioxane. This reaction led to the formation of a mixture of
products as shown in Scheme 5. The ratio of products in this case
Returning to the regioselectivity of the reaction of 1,3-dioxane,
we speculated that the poor selectivity in hydrogen abstraction by
PINO , might be improved a) by reducing the concentration of
initiator, or b) by using low concentration of 1,3-dioxane (i.e., by
performing reaction in solution). The rationale was that the ini-
tiating radical (tert-butoxyl), which is notoriously unselective,
might be playing a large role than desired in the H-atom
abstraction.
ꢀ
1
was measured using H NMR spectroscopy. A close competition in
hydrogen abstraction was observed in this case that led to major:
minor (29: 30) product ratio of 60: 40 (Scheme 5) (see
Supplementary data S2) (see Table 4).
Scheme 5. Functionalization of 1,3-dioxane via allyl transfer reaction.
To test this hypothesis, a series of experiments were performed
at varying concentration of 1,3-dioxane. The resulting product
mixture was analyzed using NMR spectroscopy to determine the
ratios of the major: minor product (Table 6). As seen in entries 1
and 2, reducing the concentration of 1,3-dioxane from 18 M to
Table 4
Allyl transfer reaction of 1,3-dioxane leading to mixture of products
Entrya
Substrate
Time (h)
Overall
reaction
yield (%)
Products
Integrated
NMR yield (%)
0.8 M did not improve selectivity of this reaction.
1
2
3
4
4
88
29
60
40
62
38
31
24
85
30
Table 6
32
Allyl transfer reaction in solution
a
Sealed tube, 120 ꢁC) (4¼0.4 M, DTBPO¼0.06 M, 1,3-dioxane¼10.0 M).
(
As anticipated, the low regioselectivity arises because the C-H
bond strength of both hydrogen atoms (H and H ) is nearly iden-
tical, 93.3 and 93.8 kcal/mol, respectively (Scheme 3).
c
d
18
Entry Substrate DTBPO 1,3-
1,3-
GC yield (%)a
Ratio
b
(
mol %) Dioxane Dioxane (3e104þ3e105) (3e104:3e105)
2
.7. Allyl transfer in solution using low concentration of
(eq.)
(M)
reagents
1
2
3
3
15
15
30
3 in
CH
3 in
CH
30
3 in
CH
18
0.8
85
66
60:40
60:40
c
One of the drawbacks of these allyl transfer reactions is the need
3
CN
3c
3
10
0.8
62
67:33
to use high concentrations of substrate, i.e., the ether was used as
both a substrate and a solvent. The versatility of this reaction would
be vastly improved if it were possible to use significantly lower
concentrations of substrate, in an inert solvent such as acetonitrile.
As a test, we examined the reaction of various concentrations of
THF with allyl-PINO compound 4 in acetonitrile solvent. As the
results in Table 5 demonstrate, decreasing the THF concentration
3
CN
4
5
4
4
15
10
18
0.8
82
60
59:41
66:34
c
3
CN
a
GC yield was calculated using internal standard diphenylmethane.
Product ratios were determined using 1H NMR spectroscopy.
3, 4¼0.07 M, DTBPO¼0.010 M, THF¼0.21 M).
b
c
(
Table 5
Similarly, to test if reducing the amount of initiator (DTBPO)
a
THF functionalization in solution (acetonitrile)
improved the selectivity, the concentration of initiator was reduced
to 10 mol % (entry 3). However, this change did not lead to signif-
icant improvement of selectivity. A similar trend was observed
when 4 was used as the substrate (entries 4 and 5).
2.8. Kinetic chain length measurements
Entry
THF (equiv)
Conc. of THF (M)
Yield (%) 33
1
2
3
4
5
1
2
3
4
10
0.07
0.14
0.21
0.28
0.71
30
45
60
62
65
In order to learn more about the mechanistic and kinetic aspects
of the ally-transfer reactions with ethers, we conducted initial ki-
netic chain-length measurements. To probe this, the initial kinetic
chain lengths (i.e., the rate of product formation relative to the rate
16
of initiator disappearance, ꢃ(v[product]/vt)/(2v[DTBPO]/vt)) were
a
(
4¼0.07 M, DTBPO¼0.010 M).
determined by following product yields as a function of time for
Please cite this article in press as: Patil, S. V.; Tanko, J. M., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.05.046

S.V. Patil, J.M. Tanko / Tetrahedron xxx (2016) 1e10
5
Z¼CO
2
Et, Ph (Table 7). The data in Table 7 illustrates that the allyl
The dimethyl acetal of benzaldehyde was synthesized using
a literature procedure (Scheme 8). A convenient and efficient
method was used for acetalization of benzaldehyde with methanol
2
using the inexpensive and water tolerant CoCl as a catalyst. This
method did not involve strong acidic or basic conditions and the
metal catalyst was recycled without the loss of activity (see
Supplementary data S2 for experimental procedure, and spectral
data for 43, 45).
17
transfer reactions are highly efficient chain reactions with kinetic
chain lengths as high as 15,000. While the chain lengths for THF
and 1,4-dioxane were both very high, the chain length was signif-
icantly shorter for 2-MeTHF. This decrease in chain length can be
attributed to the competition in hydrogen abstraction and the steric
crowding in the radical addition step. Although chain lengths in
solution were significantly lower than the reactions with neat
ethers, the results nonetheless show that it is still an efficient chain
reaction in solution (see Supplementary data S3).
Table 7
a
Kinetic chain length data for allyl transfer reactions of ethers
17
2
Scheme 8. Acetalization of benzaldehyde using methanol in the presence of CoCl .
Z
THFa
THFa (3eq. 2-MeTHF 2-MeTHF
1,4-Dioxane
In ACN)
(major
product)
(all products:
Mixture)
Reactions of dimethyl acetal of benzaldehyde with 3 and 4 were
optimized in such a way that minimum concentration of the ether
reagents and initiator could be used (see Scheme 9).
In both cases of reactions of 43 with 3 and 4, the expected acetyl
products hydrolyzed upon work-up and high yields were observed
for the desired ketone product 45 (Table 8). This type of function-
alization is not known under mild and metal-free reaction condi-
tions. The products are stable and do not isomerize to the
conjugated ketone. Especially in entry 2, where the alkene double
bond is not in conjugation with the ketone carbonyl does not
CO
Ph
2
Et 15,000 (ꢂ5000) 40 (ꢂ20)
1200 (ꢂ600) N/D
300 (ꢂ70) 1200 (ꢂ400) 8000 (ꢂ2500)
N/D 1300 (ꢂ300)
80 (ꢂ20)
a
(
3, 4¼3.5 mM, DTBPO¼0.53 mM).
2
.9. CeH functionalization of acetals
So far we have discussed the reaction of 1,3-dioxane with allyl-
PINO substrates via an allyl transfer. Since, 1,3 dioxane is a cyclic
acetal of formaldehyde (36), we extended this work to various ace-
tals. The results above show that the cyclic acetals (such as 1,3-
dioxane) can lead to multiple products owing to the competition
in hydrogen abstraction. To solve this problem, we speculated that
the difference in BDEs in acyclic dimethyl acetals such as 38 might be
sufficientlylarge that little or no H-abstractionwould occur from the
methoxyl group. Through the use of such acyclic dimethyl acetals,
we envisioned it would be possible to generate an acyl radical
equivalent in situ, which can then be used in the allyl transfer re-
action (Scheme 6). To achieve this objective, we chose aromatic al-
dehydes which can easily undergo acetal formation reaction with
methanol toyield the corresponding dimethyl acetal (see Scheme 7).
isomerize to the
Supplementary data for spectral data).
a,b-unsaturated ketone isomer (see
2.10. Amine CeH bond functionalization via allyl transfer
Similar to alkyl aromatic hydrocarbons and ethers, we envi-
sioned that the allyl transfer reaction would work for the selective
functionalization of -CeH bond containing tertiary amines. Since
BDEs of -CeH bonds of amines such as triethylamine (93.9 kcal/
mol) or N,N-dimethylaniline (93.1 kcal/mol) are similar to the
a
a
18
BDEs of benzylic hydrocarbons and ethers, we speculated them
to undergo the same chain reaction via allyl transfer. Especially,
the hydrogen abstraction from the methyl CeH bond of alkyl ar-
omatic amines (for example, N,N-dimethylaniline) could poten-
tially lead to the corresponding carbon radical, which is in
resonance with the lone pair of the electrons on the nitrogen
(Scheme 10). This stable radical might lead to the efficient allyl
transfer with the appropriate substrate. Functionalization of N,N-
dimethylaniline via allyl transfer was attempted as a pilot
reaction.
In this experiment, an interesting result was observed along
with <10% of desired product formation was recorded. Major
product of the reaction was separated and identified as a dimer of
N,N-dimethyl aniline (Scheme 11).
A likely mechanistic pathway for this reaction is shown in
ꢀ
Scheme 6. Comparison of BDEs between cyclic ether and acyclic dimethyl ether.
Scheme 12, where we speculate that PINO is involved in single
electron oxidation of aniline leading to aniline radical cation 49. 49
can potentially undergo a dimerization to form the intermediate 50
which on deprotonation by PINOꢀ undergoes re-aromatization
leading to the dimer product 51.
In 2005, Baciocchi, et al. reported a similar single electron
transfer from N,N-dimethylaniline to PINOꢀ leading to demethy-
lation of N,N-dimethylaniline (Scheme 12) This confirms that such
single electron transfer pathway is possible with the alkyl aromatic
amines and partially supports the proposed pathway for di-
merization of N,N-dimethylaniline.
19
Scheme 7. Pathway for functionalization of acyclic dimethyl acetal.
Please cite this article in press as: Patil, S. V.; Tanko, J. M., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.05.046

6
S.V. Patil, J.M. Tanko / Tetrahedron xxx (2016) 1e10
Scheme 9. Functionalization of dimethyl actetal of benzaldehyde.
Table 8
Results for the functionalization of dimethyl acetal of benzaldehyde in acetonitrile
Entrya
Z
Product (45)
Time (h)
Yield % (isolated)
1
2
CO
2
Et
24
84
89
Ph
24
Scheme 11. Attempted allyl transfer reaction of N,N-dimethylaniline with 3.
a
Sealed tube, 120 ꢁC) (3 and 4¼0.35 M, 43¼1.07 M, DTBPO¼0.05 M).
(
Scheme 10. Resonance stabilization of methyl radical in aniline.
3
. Conclusions
In conclusion, we have demonstrated an efficient method for
functionalization of various ethers and dimethyl acetal of benz-
aldehyde via an allyl transfer reaction using phthalimido-N-oxyl
radical as a chain carrier. The utility of this method is established
by observed high yields and high mass balances under metal-
free, mild, and neutral reaction conditions. A wide substrate
scope, as established by several acyclic and cyclic ethers and
acetals is demonstrated for this transformation. The reported
allyl transfer reaction was successfully carried out in-solution
using acetonitrile as solvent, which allowed successful imple-
mentation at low concentration of reagents, thus making this
a cost-effective and environmentally friendly method of ether
functionalization.
Scheme 12. Predicted pathway for dimerization of N,N-dimethylaniline.
N,N-dimethylaniline yielded the unexpected dimerized product 51,
we envisioned that the non-aromatic amines would be a better
choice for functionalization of amines via allyl transfer reaction.
ꢀ
The PINO shows good selectivity in hydrogen abstraction es-
pecially in case of 2-MeTHF, leading to 80% tertiary CeH func-
tionalization (major product), and 20% secondary CeH
functionalization (minor product). However, in case of 1,3-dioxane
moderate selectivities were observed due to the competition be-
tween two active secondary CeHs present. These two experiments
4. Experimental
4.1. General procedure for allyl transfer reaction of ethers
ꢀ
provided a valuable insight into selectivity/reactivity of PINO in
Allyl transfer reactions of ethers were run in 20 mL Pyrex
pressure tubes. In a 20 mL Pyrex tube, allyl-PINO substrate (3 or 4,
0.00090 mol) was mixed with the desired ether substrate (approx.
2e3 mL). Initiator, di-tert-butyl peroxide (0.000136 mol) was added
to the above mixture. This reaction mixture was degassed using
high vacuum by freeze-pump-thaw (3X) method and it was heated
hydrogen abstraction, thus helping us in designing a similar pro-
tocol with acetals, which in turn can be used as a method to allylate
aldehydes. A dimethyl acetal of benzaldehyde was used to dem-
onstrate this reaction, and high isolated yield for desired allylated
aldehyde product was observed. Selective functionalization of the
tertiary CeH bond was observed, supporting our hypotheses of
reactivity in these reactions. Application of this protocol in the
functionalization of substituted aryl and alkyl aldehydes is cur-
rently under development as a part of our efforts to establish the
substrate scope of this reaction. Since, the allyl transfer reaction of
ꢁ
ꢁ
at 120 C while stirring. The temperature fluctuation was ꢂ5 C and
the time of the reaction run has the accuracy of ꢂ1 min. At the end
of each reaction, the pressure tube was cooled under tap water
followed by solvent evaporation (if necessary) or liquid-liquid ex-
traction to yield the crude product. The crude product was then
Please cite this article in press as: Patil, S. V.; Tanko, J. M., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.05.046

S.V. Patil, J.M. Tanko / Tetrahedron xxx (2016) 1e10
7
purified using flash chromatography (20% ethyl acetate: 80% hex-
4.2.4. Ethyl 2-((tetrahydrothiophen-2-yl)methyl)acrylate (15). 1
H
anes). Reaction yields were determined by GC using diphenyl-
methane as an internal standard.
NMR (400 MHz, CDCl
(2 H, q, J 7.2), 3.66e3.49 (1 H, m), 3.29e3.19 (1 H, m), 2.00 (8 H,
3
) 6.25e6.12 (1 H, m), 5.61 (1 H, q, J 1.2), 4.20
13
dddd, J 178.1, 129.7, 63.6, 6.9), 1.29 (3 H, t, J 7.1). C NMR (101 MHz,
CDCl ) 166.92, 139.20, 125.84, 60.40, 46.98, 39.58, 36.95, 32.17,
0.00, 14.48. HRMS: Calculated for C10 S 201.0944, observed
MþH] 201.0946 (þ1.27).
4
.2. Experimental data
3
3
[
16 2
H O
4.2.5. Ethyl
(
2-((1,4-dioxan-2-yl)methyl)acrylate (13). 1
3
400 MHz, CDCl ) 6.24 (1 H, d, J 1.4), 5.65 (1 H, q, J 1.2), 4.21 (2 H, q, J
H
NMR
.2.1. Ethyl 2-((tetrahydrofuran-2-yl)methyl)acrylate (9). 1H NMR
400 MHz, CDCl ) 6.23 (1 H, d, J 1.3), 5.66 (1 H, d, J 1.2), 4.21 (2 H, q, J
3
4
(
13
7.1), 3.82e3.50 (6 H, m), 2.42e2.38 (2 H, m), 1.30 (3 H, t, J 7.1).
C
7.1), 4.08e3.99 (1 H, m), 3.91e3.83 (1 H, m), 3.77e3.68 (1 H, m),
3
NMR (101 MHz, CDCl ) 166.64, 136.00, 127.44, 73.57, 71.04, 66.88,
66.20, 60.92, 34.21, 14.37. HRMS: Calculated for C10
observed [MþH] 201.1127 (þ2.78).
2
.52 (2 H, d, J 6.4), 2.06e1.79 (3 H, m), 1.59e1.44 (2 H, m), 1.30 (3 H,
13
16 4
H O 201.1121,
t, J 7.1). C NMR (101 MHz, CDCl
7.20, 60.45, 37.66, 32.18, 24.18, 14.21. HRMS: Calculated for C10
185.1172, observed [MþH] 185.1180 (þ4.41 ppm).
3
) 167.31, 137.78, 126.19, 100.56,
6
16 3
H O
4
.2.6. Ethyl 2-((tetrahydro-2H-pyran-2-yl)methyl)acrylate (11). 1
H
3
NMR (400 MHz, CDCl ) 6.20 (1 H, d, J 1.7), 5.62 (1 H, dd, J 2.7, 1.3),
4
.2.2. Ethyl 2-((2-methyltetrahydrofuran-2-yl)methyl)acrylate (25)þ
1
4.20 (2 H, q, J 7.2), 4.00e3.90 (1 H, m), 3.53e3.32 (2 H, m),
mixture of 27. H NMR (400 MHz, CDCl
5
2
3
) 6.19 (1 H, d, J 1.8),
.60e5.59 (1 H, m), 4.25e4.15 (3 H, m), 3.80 (2 H, dd, J 14.7, 6.8),
.55 (3 H, q, J 13.5), 1.98e1.86 (2 H, m), 1.84e1.74 (1 H, m), 1.68e1.57
13
2
(
.52e2.36 (2 H, m), 1.90e1.35 (7 H, m), 1.29 (3 H, t, J 7.1). C NMR
101 MHz, CDCl ) 167.32, 137.51, 126.90, 76.10, 68.72, 60.58, 39.13,
199.1329,
3
31.79, 25.93, 23.34, 14.26. HRMS: Calculated for C11
18
H O
3
(
1
2 H, m), 1.29 (4 H, td, J 7.1, 1.6), 1.18 (3 H, s). (Expansion in the
.31e1.39 region shows evidence of regioisomers (cis and trans 27)
observed [MþH] 199.1322 (ꢃ3.17 ppm).
13
in the form of 3H, d). C NMR (101 MHz, CDCl
27.52, 81.92, 67.51, 60.77, 41.49, 36.72, 25.75, 21.28, 14.23. HRMS:
Calculated for C11
(3e95) 199.1329, observed [MþH] 199.1325
ꢃ2.06 ppm).
3
) 168.25, 137.47,
1
18 3
H O
(
4
.2.7. Ethyl 4-(tert-butoxy)-2-methylenepentanoate (6). 1H NMR
400 MHz, CDCl ) 6.17 (1 H, q), 5.57 (1 H, s), 4.22 (2 H, q), 3.87e3.78
1 H, m), 2.48 (1 H, dd), 2.34 (1 H, dd), 1.30 (5 H, t), 1.16 (11 H, s), 1.09
(
(
(
3
13
4 H, d). C NMR (101 MHz, CDCl
3
) 167.38, 138.54, 127.04, 73.35,
5.86, 60.48, 42.02, 28.61, 22.55, 14.09. HRMS: Calculated for
215.1642, observed [MþH] 215.1626 (ꢃ7.36).
6
C
12 22 3
H O
4
(
(
.2.3. Ethyl
400 MHz, CDCl
2 H, q), 3.45e3.33 (2 H, m), 2.51 (1 H, ddd, J 13.8, 6.6, 1.0), 2.27 (1 H,
4-ethoxy-2-methylenepentanoate
(5). 1
H
NMR
3
) 6.11 (1 H, dd, J 4.1,1.9), 5.52 (1 H, dq, J 1.7, 1.2), 4.12
13
ddd, J 13.8, 6.1, 1.0), 1.22 (3 H, td, J 7.1, 2.4), 1.11e1.03 (5 H, m).
C
NMR (101 MHz, CDCl
9.27, 19.44, 15.57, 13.97. HRMS: Calculated for C10
observed [MþH] 187.1325 (ꢃ1.82 ppm).
3
) 167.16, 137.72, 126.80, 73.63, 63.51, 60.34,
3
18 3
H O
187.1329,
4
.2.8. Ethyl 2-((1,3-dioxan-2-yl)methyl)acrylate (30þ32). 1H NMR
3
(400 MHz, CDCl ) 6.24 (2 H, dd, J 3.8, 1.5), 5.68 (2 H, dd, J 3.1, 1.2),
4.74 (1 H, t), 4.21 (3 H, q, J 7.1), 4.08 (3 H, dd, J 6.0, 4.7), 4.05e3.98
(
1 H, m), 3.88e3.58 (4 H, m), 2.62 (3 H, dd, J 5.4, 0.9), 2.24e1.96 (2 H,
13
3
m), 1.30 (10 H, s). C NMR (101 MHz, CDCl ) 177.89, 135.50, 128.46,
Please cite this article in press as: Patil, S. V.; Tanko, J. M., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.05.046

8
S.V. Patil, J.M. Tanko / Tetrahedron xxx (2016) 1e10
1
C
23.37, 67.19, 60.15, 37.66, 25.44, 13.61. HRMS: Calculated for
66.39, 38.16. HRMS: Calculated for C13
[MþH] 205.1229 (þ0.87 ppm).
H
16
O
2
205.1225, observed
H
10 16
O
4
201.1112, observed 201.110 (þ2.17 ppm).
4.2.13. (4-Ethoxypent-1-en-2-yl)benzene (7). 1
CDCl
.64e3.26 (1 H, m), 2.93 (1 H, ddd, J 14.0, 6.0, 1.1), 2.50 (1 H, ddd, J
H NMR (400 MHz,
) 7.49e7.17 (1 H, m), 5.32 (1 H, d, J 1.6), 5.14 (1 H, d, J 1.3),
.2.9. Ethyl 2-(benzo[1,3]dioxol-2-ylmethyl)acrylate (17). 1H NMR
400 MHz, CDCl ) 6.89e6.69 (2 H, m), 6.37 (1 H, d, J 1.2), 6.31 (1 H,
t, J 5.1), 5.80 (1 H, q, J 1.2), 4.25 (1 H, q, J 7.1), 3.03e2.88 (1 H, m),
4
(
3
3
3
13
.32 (1 H, t, J 7.1). 1 C NMR (101 MHz, CDCl
33.94, 129.08, 121.71, 109.50, 108.87, 60.77, 37.35, 13.92. HRMS:
Calculated for C13
235.0965, observed [MþH] 235.0975
3
14.0, 7.3, 1.0), 1.14 (1 H, t, J 6.9). C NMR (101 MHz, CDCl
41.39, 128.27, 127.19, 126.35, 114.68, 73.73, 63.67, 42.75, 19.51,
5.57. HRMS: Calculated for C13
18O 191.143, observed [MþH]
91.1427 (ꢃ1.72 ppm).
3
) 145.92,
1
3
) 166.29, 147.09,
1
1
1
H
14 4
H O
1
(þ4.5 ppm).
.2.10. 2-(2-Phenylallyl)tetrahydrofuran (10). 1H NMR (400 MHz,
4.2.14. 2-(2-Phenylallyl)-1,3-dioxane (29) (major 60%) and 4-(2-
phenylallyl)-1,3-dioxane (31) (minor 40%). H NMR (400 MHz,
4
1
CDCl
.99e3.86 (1 H, m), 3.75e3.67 (1 H, m), 2.91 (1 H, ddd, J 14.3, 6.4,
.1), 2.62 (1 H, ddd, J 14.3, 6.9, 0.9), 1.98e1.75 (3 H, m), 1.53 (1 H, td, J
3
) 7.49e7.23 (4 H, m), 5.36 (1 H, d, J 1.3), 5.18 (1 H, d, J 1.2),
3
CDCl ) 7.61e7.04 (5 H, m), 5.39 (1 H, dd, J 9.5, 1.4), 5.19 (1 H, dq, J
3
1
2.3, 1.3), 4.68e4.52 (1 H, m), 4.15e3.99 (1 H, m), 3.80e3.50 (2 H,
1
7
1
13
C H
13
.5, 3.0). 1 C NMR (101 MHz, CDCl
26.19,114.41, 77.54, 67.80, 41.58, 31.14, 25.54. HRMS: Calculated for
16O 189.1274, observed [MþH] 189.1259 (ꢃ7.71 ppm).
3
m), 2.84 (1 H, dd, J 5.3,1.1), 2.08 (1 H, ddd, J 13.4,13.0,10.0). C NMR
101 MHz, CDCl ) 144.30, 143.01, 140.81, 140.64, 128.41, 128.29,
27.60, 127.46, 126.17, 126.15, 115.21, 100.69, 93.47, 74.82, 67.20,
3
) 145.49, 141.22, 128.39, 127.61,
(
3
1
6
2
6.51, 42.01, 41.08, 31.62, 25.86. HRMS: Calculated for C13
05.1223, observed [MþH] 205.1225 (þ0.89 ppm).
16 2
H O
4
.2.11. 2-Methyl-2-(2-phenylallyl)tetrahydrofuran (26þ28). 1H NMR
1
4
CDCl
3
1
1
2
.2.15. (4-(tert-Butoxy)pent-1-en-2-yl)benzene (8). H NMR (400 MHz,
(
400 MHz, CDCl
3
) 7.36 (2 H, d, J 50.6), 5.34 (1 H, s), 5.17 (1 H, s), 3.75
13
3
) 7.54e7.20 (1 H, m), 5.32 (1 H, d, J 1.7), 5.13 (1 H, dd, J 2.2, 1.4),
.78e3.50 (1 H, m), 2.85 (1 H, ddd, J 13.8, 5.5, 1.0), 2.52 (1 H, ddd, J
3.8, 8.1, 0.7), 1.22e1.03 (2 H, m). C NMR (101 MHz, CDCl ) 146.12,
3
41.09, 128.41, 127.40, 126.31, 114.74, 73.41, 66.21, 45.41, 28.52,
(
1 H, ddt, J 21.9, 8.2, 6.8), 2.78 (1 H, s), 1.85 (2 H, s), 1.12 (1 H, s).
C
NMR (101 MHz, CDCl
8
C
3
) 146.08, 142.87, 128.13, 127.10, 126.50, 116.93,
2.81, 66.83, 46.07, 36.03, 26.36, 25.94. HRMS: Calculated for
18O 203.143, observed [MþH] 203.1414 (ꢃ7.86 ppm).
13
14
H
2.64. HMRS: Difficult to ionize using ESI or APCI ionization
methods (GCeMS analysis can be found in Supplementary data S6,
Fig. S11.).
4
.2.12. 2-(2-Phenylallyl)-1,4-dioxane (14). 1
CDCl ) 7.50e7.15 (4 H, m), 5.36 (1 H, d, J 1.4), 5.15 (1 H, q, J 1.2),
.86e3.46 (5 H, m), 3.29 (1 H, dd, J 11.4, 9.8), 2.76 (1 H, ddd, J 14.4,
H NMR (400 MHz,
1
3
4.2.16. 2-(2-Phenylallyl)tetrahydro-2H-pyran(12). H NMR (400 MHz,
3
6
3
CDCl ) 7.47e7.38 (2 H, m), 7.31 (3 H, dddd, J 13.1, 11.6, 5.8, 3.6), 5.34
(1 H, d, J 1.6), 5.14 (1 H, dd, J 2.6, 1.3), 4.03e3.89 (1 H, m), 3.47e3.24
(2 H, m), 2.83 (1 H, ddd, J 14.3, 6.5,1.1), 2.55 (1 H, ddd, J 14.3, 6.7,1.0),
13
.5, 1.2), 2.52 (1 H, ddd, J 14.5, 7.0, 1.0). C NMR (101 MHz, CDCl
3
)
143.89, 140.37, 128.40, 127.65, 126.15, 115.01, 73.53, 71.05, 66.86,
Please cite this article in press as: Patil, S. V.; Tanko, J. M., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.05.046

S.V. Patil, J.M. Tanko / Tetrahedron xxx (2016) 1e10
9
1
.88e1.16 (7 H, m). 13C NMR (101 MHz, CDCl
3
) 145.14, 140.98,
129.04, 128.45, 128.35, 127.57, 126.26, 114.82, 41.96. HRMS: Calcu-
lated for C16
14O, 223.2811, observed 223. 1112 (þ5.69 ppm).
128.45, 127.20, 126.18, 75.94, 68.53, 42.76, 31.85, 26.14, 23.24.
H
HMRS: Calculated for C14
H18O 203.143, observed [MþH] 203.1436
(þ2.54 ppm).
1
4
.2.21. Ethyl 2-methylene-4-oxo-4-phenylbutanoate (45, Z¼CO
NMR (400 MHz, CDCl ) 7.99 (2 H, ddd, J 7.1, 2.3, 1.2), 7.65e7.41 (4 H,
m), 6.44e6.36 (1 H, m), 5.69 (1 H, q, J 1.0), 4.21 (2 H, q, J 7.2), 4.00
2
Et). H
1
3
4
.2.17. 2-(2-Phenylallyl)tetrahydrothiophene(16). H NMR (400 MHz,
3
CDCl ) 7.47e7.07 (5 H, m), 5.32e5.24 (1 H, m), 5.17e5.04 (1 H, m),
13
(2 H, d, J 1.0), 1.26 (4 H, t, J 7.1). C NMR (101 MHz, CDCl
3
) 196.76,
13
2
.90e2.68 (10 H, m),1.96e1.83 (8 H, m),1.26 (7 H, s), 0.87 (6 H, s). C
1
66.29, 134.82, 133.25, 128.62, 128.30, 128.23, 61.08, 41.81, 13.93.
3
NMR (101 MHz, CDCl ) 147.09, 140.87, 128.28, 127.45, 126.20, 113.83,
HRMS: Calculated for C13
H O
15 3
219.1016, observed 219.101 (ꢃ2.63).
36.73, 31.74, 30.93, 22.64, 14.17. HRMS: Calculated for C13
05.1045, observed [MþH] 205.1052 (þ3.27 ppm).
H16 S:
2
Acknowledgements
Acknowledgment is made to the donors of American Chemical
Society, Petroleum Research Fund for the support of this project.
The authors also wish to thank Mr. Mehdi Ashraf-Khorassani for his
help with HRMS and ESI-MS analyses, and Mr. Justin Curtiss for
synthetic assistance.
Supplementary data
4
CDCl
6
.2.18. 2-(2-Phenylallyl)benzo[1,3]dioxole (18). 1H NMR (400 MHz,
) 7.56e7.21 (2 H, m), 6.93e6.71 (6 H, m), 6.23 (1 H, t, J 5.1),
.00e5.87 (3 H, m), 5.52 (1 H, d, J 1.1), 5.32 (1 H, d, J 1.1), 3.16 (1 H,
Supplementary data (Supplementary data for procedures of
3
1
13
synthetic reactions, H and C NMR spectral data, HRMS data, ki-
netic chain length calculations, and GCeMS analyses of regioiso-
meric products) related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2016.05.046.
13
dd, J 5.1, 1.0). C NMR (101 MHz, CDCl
28.30, 127.88, 126.32, 121.72, 116.23, 108.88, 100.36, 40.58. HMRS:
Calculated for C16
237.0910, observed [MþH] 237.0927
3
) 147.50, 141.36, 140.35,
1
12 2
H O
(þ7.1).
References and notes
1. Frontmatter. In Handbook of CeH Transformations; Dyker, G., Ed.; Wiley-VCH
Verlag GmbH: 2008; pp IeXXVI.
2
. (a) Chen, C.; Crich, D.; Papadatos, A. J. Am. Chem. Soc. 1992, 114, 8313e8314; (b)
Muramatsu, H.; Moriguchi, S.; Inukai, K. J. Org. Chem. 1966, 31, 1306e1309.
. (a) Davies, H. M. L.; Hansen, T. J. Am. Chem. Soc. 1997, 119, 9075e9076; (b)
Davies, H. M. L.; Yang, J.; Nikolai, J. J. Organomet. Chem. 2005, 690, 6111e6124;
3
(c) Davies, H. M. L.; Grazini, M. V. A.; Aouad, E. Org. Lett. 2001, 3, 1475e1477; (d)
Davies, H. M. L.; Manning, J. R. Nature 2008 451e417; (e) Davies, H. M. L.;
Beckwith, R. E. J.; Antoulinakis, E. G.; Jin, Q. J. Org. Chem. 2003, 68, 6126e6132;
(f) Davies, H. M. L.; Hedley, S. J.; Bohall, B. R. J. Org. Chem. 2005, 70,
4
.2.19. (Dimethoxymethyl)benzene (43). Based on a literature pro-
20
cedure. A mixture of benzaldehyde (2 g, 0.01886 mol), CoCl
dry, 0.121 g, 0.000943 mol) and dry methanol (80 mL) were
2
10737e10742; (g) Davies, H. M. L.; Hansen, T.; Churchill, M. R. J. Am. Chem. Soc.
(
2000, 122, 3063e3070; (h) Díaz-Requejo, M. M.; Belderraín, T. R.; Nicasio, M. C.;
ꢁ
ꢀ
refluxed at 110 C for 3 h, using CaCl
2
guard tube over reflux
Trofimenko, S.; Perez, P. J. J. Am. Chem. Soc. 2002, 124, 896e897.
4
. (a) Perez, D.; Leighton, F.; Aspee, A.; Aliaga, C.; Lissi, E. Biol. Res. 2000, 33; (b)
Wang, P.; Adams, J. J. Am. Chem. Soc. 1994, 116, 3296e3305.
. (a) Muramatsu, H.; Inukai, K.; Ueda, T. Bull. Chem. Soc. Jpn. 1967, 40, 903e907;
(b) Chambers, R. D.; Fuss, R. W.; Jones, M. J. Fluorine Chem. 1990, 49, 409e419;
condenser. Methanol was evaporated under reduced pressure.
Ethyl acetate (5 mL) was added to the residue. Co(II) salt was fil-
tered and filtrate was passed through a short column of alumina
5
(c) Chen, J.; Krichmeier, R. L.; Shreeve, J. M. Inorg. Chem. 1996, 35, 6676e6681.
(
basic) using 5% ethyl acetate in hexane. Procedure yielded pure
6
. (a) Gong, J.; Fuchs, P. L. J. Am. Chem. Soc. 1996, 118, 4486e4487; (b) Xiang, J.;
Fuchs, P. L. J. Am. Chem. Soc. 1996, 118, 11986e11987; (c) Xiang, J.; Jiang, W.;
Gong, J.; Fuchs, P. L. J. Am. Chem. Soc. 1997, 119, 4123e4129; (d) Alkema, H. J.;
Arens, J. F., Chemistry of acetylenic ethers XLVI Addition of thiols to acetylenic
ethers. 1960, 79, 1257e1281.
1
dimethyl acetal product which was characterized by NMR.
NMR (400 MHz, CDCl ) 7.50e7.30 (4 H, m), 5.41 (1 H, s), 3.34 (6 H,
s). C NMR (101 MHz, CDCl ) 138.20, 128.53, 128.07, 126.63,
H
3
13
3
103.25, 52.76.
7
. Hirano, K.; Sakaguchi, S.; Ishii, Y. Tetrahedron Lett. 2002, 43, 3617e3620.
. Liu, Z.-Q.; Sun, L.; Wang, J.-G.; Han, J.; Zhao, Y.-K.; Zhou, B. Org. Lett. 2009, 11,
437e1439.
. (a) Yamamoto, Y.; Yamada, K.-I.; Tomioka, K. Tetrahedron Lett. 2004, 45,
95e797; (b) Yamada, K. I.; Yamamoto, Y.; Tomioka, K. Org. Lett. 2003, 5,
797e1799; (c) Yamada, K. i; Yamamoto, Y.; Maekawa, M.; Tomioka, K. J. Org.
8
9
1
7
1
Chem. 2004, 69, 1531e1534; (d) Yamamoto, Y.; Maekawa, M.; Akindele, T.;
Yamada, K.-I.; Tomioka, K. Tetrahedron Lett. 2005, 61, 379e384; (e) Clerici, A.;
Cannella, R.; Pastori, N.; Panzeri, W.; Porta, O. Tetrahedron Lett. 2006, 62,
5
986e5994.
.2.20. 1,3-Diphenylbut-3-en-1-one (45, Z¼Ph). 1H NMR (400 MHz,
10. (a) Tanko, J. M.; Sadeghipour, M. Angew. Chem. 1999, 111, 219e222; (b) Struss, J.
A.; Mitra, S.; Tanko, J. M. Tetrahedron Lett. 2009, 50, 2119e2120; (c) Patil, S.;
Chen, L.; Tanko, J. M. Eur. J. Org. Chem. 2014, 2014, 502e505; (d) Patil, S.; Chen,
L.; Tanko, J. M. Tetrahedron Lett. 2014, 55, 7029e7033.
4
3
CDCl ) 8.00e6.76 (1 H, m), 5.49 (1 H, dd, J 1.3, 0.5), 5.02 (1 H, q, J
1
3
1
3
.3), 3.84 (1 H, s). C NMR (101 MHz, CDCl ) 193.54, 147.25, 139.50,
Please cite this article in press as: Patil, S. V.; Tanko, J. M., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.05.046

10
S.V. Patil, J.M. Tanko / Tetrahedron xxx (2016) 1e10
1
1. Mayo, F. R. Free Radicals InKochi, Jay K., Ed.Vol. II; Wiley: New York, NY, 1973; Vol.
II, p 906; J. Poly. Sci.: Poly. Lett. Ed. 1974, 12 (9), 536e538.
2. Blanksby, S. J.; Ellison, G. B. Acc. Chem. Res. 2003, 36, 255e263.
3. Koshino, N.; Saha, B.; Espenson, J. H. J.Org. Chem. 2003, 68, 9364e9370.
A. W.; Kel’in, A. V.; Gevorgyan, V. Angew. Chem., Int. Ed. 2004, 43, 2280e2282;
(d) Antoniotti, S.; Genin, E.; Michelet, V.; Gen e^ t, J.-P. J. Am. Chem. Soc. 2005, 127,
9976e9977.
1
1
16. Espenson, J. H. Chemical Kinetics and Reaction Mechanisms; McGraw-Hill: New
York, NY, 1995.
17. Velusamy, S.; Punniyamurthy, T. Tetrahedron Lett. 2004, 45, 4917e4920.
18. Luo, Y.-R. Tabulated BDEs of CeH Bonds In Handbook of Bond Dissociation En-
ergies in Organic Compounds; CRC Press: 2002.
1
4. (a) Jaenicke, L. Ionophore Polyether Antibiotics e Naturally Occurring Acid
Ionophores. Bd. 1: Biology InWestley, Von J. W., Ed.XVII, 465 S., SFr; Marcel
Dekker: New York e Basel, 1982; XVII, 465 S., SFr, p 185; Nachrichten aus Chemie,
Technik und Laboratorium 1983, 31 (9), 724e724; (b) Alali, F. Q.; Liu, X.-X.;
McLaughlin, J. L. J. Nat. Prod. 1999, 62, 504e540; (c) Harmange, J.-C.; Figad eꢁ re, B.
19. Baciocchi, E.; Bietti, M.; Gerini, M. F.; Lanzalunga, O. J. Org. Chem. 2005, 70,
5144e5149.
Tetrahedron: Asymmetry 1993, 4, 1711e1754.
15. (a) Wolfe, J. P.; Rossi, M. A. J. Am. Chem. Soc. 2004, 126, 1620e1621; (b) Qian, H.;
20. Punniyamurthy, T.; Velusamy, S.; Iqbal, J. Chem. Rev. 2005, 105, 2329e2364.
Han, X.; Widenhoefer, R. A. J. Am. Chem. Soc. 2004, 126, 9536e9537; (c) Sromek,
Please cite this article in press as: Patil, S. V.; Tanko, J. M., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.05.046