Tetrabutylammonium iodide catalyzed synthesis of allylic ester with tert -butyl hydroperoxide as an oxidant

Article abstract of DOI:10.1021/ol3013606

A metal-free C-H oxidation for the construction of allylic esters has been developed. The use of a commercially available and inexpensive catalyst and oxidant, and readily available starting materials, coupled with the operational simplicity of the reacti

Full text of DOI:10.1021/ol3013606

ORGANIC
LETTERS
2012
Vol. 14, No. 13
3384–3387
Tetrabutylammonium Iodide Catalyzed
Synthesis of Allylic Ester with tert-Butyl
Hydroperoxide as an Oxidant
Erbo Shi,† Ying Shao,‡ Shulin Chen,† Huayou Hu,z Zhaojun Liu,† Jie Zhang,† and
Xiaobing Wan*,†
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry,
Chemical Engineering and Materials Science, Soochow University, Suzhou 215123,
P. R. China, Key Laboratory of Fine Petrochemical Engineering, Changzhou University,
Changzhou 213164, P. R. China, and Key Laboratory for Chemistry of
Low-Dimensional Materials, School of Chemistry and Chemical Engineering,
Huaiyin Normal University, Huaian 223300, P. R. China
wanxb@suda.edu.cn
Received May 17, 2012
ABSTRACT
A metal-free CÀH oxidation for the construction of allylic esters has been developed. The use of a commercially available and inexpensive catalyst
and oxidant, and readily available starting materials, coupled with the operational simplicity of the reaction, renders the methodology a useful
alternative to other approaches typically employed in the synthesis of allylic esters.
The selective oxidation of allylic CÀH bonds, for the
construction of highly valuable R-functionalized alkenes,
has drawn much attention in recent years. This atom-
economical process avoids prefunctionalization of CÀH
bonds, thus making synthetic schemes shorter, cleaner,
and more efficient.1 To date, several transition metal
catalyzed allylic CÀH oxidations have developed.2 Allylic
esters are ubiquitous structural motifs and occur in many
natural products.3 They also serve as important building
blocks in organic synthesis4 and have been traditionally
synthesized by acylation of the corresponding allylic
alcohols.5 Recently, a palladium-catalyzed atom-economical
synthesis of allylic esters from carboxylic acids and
† Soochow University.
‡ Changzhou University.
z Huaiyin Normal University.
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r
10.1021/ol3013606
Published on Web 06/25/2012
2012 American Chemical Society

monosubstituted olefins by CÀH bond oxidation has
constituted a significant breakthrough in this area.6 The
coupling of allenes7 or terminal alkynes8 with carboxylic
acids has also provided a powerful protocol for the for-
mation of allylic esters. Both of these elegant reactions
proceeded via a π-allyl metal intermediate, generated in
situ from the reaction between a CÀH bond and transition
metal catalyst.
Table 1. Optimization of Reaction Conditionsa
entry
catalyst
oxidant
TBHP
yieldb
1
2
3
4
5
6
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
87%
N.D.c
N.D.
N.D.
N.D.
N.D.
NaClO
H2O2
Scheme 1. Allylic Ester Synthesis via Radical Coupling
O2
BQ
Di-tert-butyl
peroxoide
À
7
Bu4NI
À
N.D.
N.D.
N.D.
N.D.
N.D.
71%d
50%e
8
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
9
Bu4NCl
Bu4NBr
Bu4NOH
Bu4NI
Bu4NI
10
11
12
13
The KharaschÀSosnovsky reaction,9 a Cu-catalyzed
esterification of an allylic CÀH bond with tert-butyl
peresters, is a classical method of allylic ester synthesis.
We herein describe a new, highly selective radical coupling
strategy to construct allylic esters. Compared with tert-
butyl peresters, carboxylic acids are commercially avail-
able or easily prepared. Free radical chemistry has ad-
vanced tremendously since its discovery in 1900;10 however,
the highly selective coupling of different radical species still
remains a challenge in radical chemistry.11
a Reaction conditions: 0.5 mmol of 4-chlorobenzoic acid 1b, 2.0
mmol of cyclohexene 2a, 20 mol % catalyst, 1.5 equiv of TBHP (70%
aqueous solution) in 2.0 mL of benzene at 80 °C for 8 h. b Isolated yield.
c Not detected. d 1.0 mmol of cyclohexene 2a was used. e 5 mol % catalyst
was used.
were encouraged by the initial result as it proved the
feasibility of coupling of acyloxy and allylic radicals. To
determine the utility of the transformation, commercially
inexpensive and abundant carboxylic acids were investi-
gated as potential acyloxy radical donors. Extending our
recent studies involving tetrabutylammonium iodide
(TBAI) catalyzed chemical reactions,13 we envisioned
converting carboxylic acids and alkenes to the correspond-
ing allylic ester using a similar, metal-free approach. 20 mol %
TBAI/1.5 equiv of TBHP (tert-butyl hydroperoxide) in
benzene at 80 °C was found by screening to give a high
yield (87%) of the desired allylic ester 3b without requir-
ing an inert atmosphere (Table 1, entry 1).
Table 1 reveals the effect of different catalysts and
oxidants on the efficiency of the allylic CÀH oxidation
process. The choice of oxidant was critical to the conver-
sion, as no desired allylic ester 3b was detected when any
oxidant other than TBHP was employed (entries 2À6).
To test our hypothesis, benzoyl peroxide, a well-known
precursor to acyloxy radicals,12 was coupled with cyclo-
hexene. This formedthe desiredallylicester3ain24% yield
(Scheme 1, GC yield). In spite of the low yield obtained, we
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Org. Lett., Vol. 14, No. 13, 2012
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No significant amount of 3b was observedin the absence of
TBAI or TBHP (entries 7À8). In addition, Bu4NCl,
Bu4NBr, and Bu4NOH failed to catalyze the formation
of the desired 3b, indicating that the use of iodide is also
critical for this transformation (entries 9À11).
Figure 2. Scope of carboxylic acids. (a) Reaction conditions:
0.5 mmol of carboxylic acids 1, 2.0 mmol of cyclohexene 2a,
20 mol % TBAI, 1.5 equiv of TBHP (70% aqueous solution) in
2.0 mL of benzene at 80 °C for 8 h. (b) 50 mol % TBAI was used.
Figure 1. Scope of aryl carboxylic acids. (a) Reaction conditions:
0.5 mmol of aryl carboxylic acids 1, 2.0 mmol of cyclohexene 2a,
20 mol % TBAI, 1.5 equiv of TBHP (70% aqueous solution) in
2.0 mL of benzene at 80 °C for 8 h.
With optimized conditions in hand, a series of substi-
tuted aryl carboxylic acids were investigated, as shown in
Figure 1. Both electron-donating and -withdrawing aryl
carboxylic acids could be successfully converted to the
corresponding allylic esters in moderate to excellent yields.
In addition, a high level of functional group tolerance was
observed, with halides, ethers, sulfones, Boc-protected
amines, nitriles, amides, tosylates, and nitro groups being
unaffected by the reaction.
Figure 3. Scope of alkenes. (a) Reaction conditions: 0.5 mmol of
4-chlorobenzoic acid 1b, 2.0 mmol of alkenes 2, 20 mol % TBAI,
1.5 equiv of TBHP (70% aqueous solution) in 2.0 mL of benzene
at 80 °C for 8 h. (b) 50 mol % TBAI was used.
To highlight the utility of this transformation, other
types of carboxylic acids were subjected to the standard
reaction conditions. These results are presented in Figure 2.
A variety of heteroaryl acids, including thiophene, furan,
benzofuran, indazole, and phthalimide, were coupled with
cyclohexene 2a, providing the corresponding allylic esters
in good yields. Treatment of R,β-unsaturated carboxylic
acids, such as crotonic acid and trans-cinnamic acid, with
cyclohexene 2a afforded the anticipated cross-coupling
products 4f and 4g in 76% and 87% yield, respectively. It
is noteworthy that protected amino acids were also suitable
reaction partners under the standard conditions (products
4hÀ4j). A series of aliphatic carboxylic acids also provided
the expected allylic esters 4kÀ4n in high yields, when
subjected to the standard reaction conditions.
4-chlorobenzoic acid 1b to afford 5a in good yield. Nota-
bly, benzylic CÀH bonds could also be oxidized to the
corresponding benzylic esters under the optimized condi-
tions, leading to 5b, 5c, and 5i in low to good yields. When
terminal alkenes were subjected to the reaction conditions,
including vinylcyclohexane and allylbenzene, linear allylic
esters 5d and 5e were obtained selectively in 72% and 66%
yields, respectively. A trisubstituted alkene was also trans-
formed into the desired product 5f in satisfactory yield
when reacted with 1b. Even tetrasubstituted alkenes pro-
vided the anticipated allylic esters in good yields (products
5g and 5h). To the best of our knowledge, this is the first
reported example of allylic CÀH oxidation using tetrasub-
stituted alkenes as reactants.
To further explore the potential of our methodology, a
variety of alkenes were investigated as shown in Figure 3.
In contrast to the transition metal catalyzed reaction,6
even multiply substituted alkenes reacted successfully in
the allylic ester synthesis. Cyclopentene reacted well with
Further experiments were conducted to elucidate the
mechanism of the allylic CÀH oxidation. The reaction of
sodium benzoate and cyclohexene did not result in the
formation of allylic ester 3a, indicating that the reaction of
3386
Org. Lett., Vol. 14, No. 13, 2012

On the basis of these results, a plausible catalytic cycle is
presented in Scheme 4. Initially, TBHP decomposes to
generate the tert-butoxyl and tert-butylperoxy radicals
(Scheme 4a). These radicals subsequently abstract hydro-
gen atoms from the alkene and carboxylic acid15 toprovide
both the allylic radical A and acyloxy radical B, respec-
tively (Scheme 4b and c). Finally, the coupling of A and B
forms the desired allylic ester (Scheme 4d).
Scheme 2. Investigation into the Reaction Mechanism
a carboxylate anion and allyl cation were not involved in
the allylic ester synthesis (Scheme 2).
Scheme 4. Proposed Catalytic Cycle
Scheme 3. Investigation into the Reaction Mechanism
In summary, we have successfully developed the first
metal-free allylic ester synthesis allowing for the selective
coupling of acyloxy and allylic radicals using TBAI and
TBHP. This radical process is free from both metal and
photolysis conditions and makes use of commercially
available, inexpensive, and abundant starting materials.
Further investigations of both intramolecular and asym-
metric versions of the reaction are currently underway in
our laboratory.
3-Chloroperoxybenzoic acid, a known acyloxy radical
donor,14 was also a suitable reaction partner for the
transformation (Scheme 3a). Notably, a tert-butyl peres-
ter, from the coupling of the acyloxy and tert-butoxyl
radicals, was detected by LC-MS in the reaction mixture
(Scheme 3b). When hippuric acid was used as a reactant,
both the tert-butyl perester and decarboxylation product
were observed as byproducts (Scheme 3c). When TEMPO,
a well-known radical-trapping reagent, was introduced to
the reaction mixture, the formation of the desired allylic
ester was completely suppressed. Compound 6, an adduct
of TEMPO and the allylic radical, was isolated from this
test in a yield of 31% (Scheme 3d). Based upon the above
results, we prefer that the reaction involves the coupling of
acyloxy and allylic radicals in the catalytic cycle of the
allylic ester synthesis.
Acknowledgment. A project funded by the Priority
Academic Program Development of Jiangsu Higher Edu-
cation Institutions (PAPD) and NSFC (21072142). Prof.
Dr. H. Hu is grateful to Jiangsu Province NSF (No.:
BK2011408) and Jiangsu Province Department of Educa-
tion (No. 10KJB150002) for their financial support.
Supporting Information Available. Experimental de-
tails, 1H and 13C NMR spectra. This material is available
free of charge via the Internet at http://pubs.acs.org.
(14) Groenhof, A. R.; Ehlers, A. W.; Lammertsma, K. J. Phys. Chem.
A 2008, 112, 12855.
(15) Silbert, L. S. J. Am. Oil Chem. Soc. 1969, 46, 615.
The authors declare no competing financial interest.
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