Copper-catalyzed oxidative dehydrogenative functionalization of alkanes to allylic esters

Article abstract of DOI:10.1016/j.ica.2019.119190

Herein, we report a general, efficient and solvent-free method for the one-pot synthesis of allylic esters via dehydrogenation of unactivated alkanes and subsequent oxidative cross coupling with different substituted carboxylic acids. A simple, well defined and air stable Cu(II)-complex, [Cu(MeTAA)], featuring a tetraaza-macrocyclic ligand (tetramethyltetraaza[14]annulene (MeTAA)) is used as the catalyst. A wide variety of substituted allylic esters were synthesized in high yields starting from readily available starting materials. Control reactions were carried out to understand the reaction sequence and the plausible mechanism.

Full text of DOI:10.1016/j.ica.2019.119190

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Research paper
Copper-Catalyzed Oxidative Dehydrogenative Functionalization of Alkanes to
Allylic Esters
Rakesh Mondal, Gargi Chakraborty, Kaj M. van Vliet, Nicolaas P. van Leest,
Bas de Bruin, Nanda D. Paul
PII:
S0020-1693(19)31073-4
https://doi.org/10.1016/j.ica.2019.119190
ICA 119190
DOI:
Reference:
Inorganica Chimica Acta
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23 July 2019
23 September 2019
1 October 2019
Please cite this article as: R. Mondal, G. Chakraborty, K.M. van Vliet, N.P. van Leest, B. de Bruin, N.D. Paul,
Copper-Catalyzed Oxidative Dehydrogenative Functionalization of Alkanes to Allylic Esters, Inorganica Chimica
Acta (2019), doi: https://doi.org/10.1016/j.ica.2019.119190
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Copper-Catalyzed Oxidative Dehydrogenative Functionalization of
Alkanes to Allylic Esters
Rakesh Mondal,[a] Gargi Chakraborty,[a] Kaj M. van Vliet,[b] Nicolaas P. van Leest,[b] Bas de
Bruin[b] and Nanda D. Paul[a]*
[a]Department of Chemistry, Indian Institute of Engineering Science and Technology, Shibpur,
Botanic Garden, Howrah 711103, India
[b]Homogeneous Catalysis Group, van ’t Hoff Institute for Molecular Sciences, University of
Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands

Abstract. Herein, we report a general, efficient and solvent-free method for the one-pot
synthesis of allylic esters via dehydrogenation of unactivated alkanes and subsequent oxidative
cross coupling with different substituted carboxylic acids. A simple, well defined and air stable
Cu(II)-complex,
[Cu(MeTAA)],
featuring
a
tetraaza-macrocyclic
ligand
(tetramethyltetraaza[14]annulene (MeTAA)) is used as the catalyst. A wide variety of substituted
allylic esters were synthesized in high yields starting from readily available starting materials.
Control reactions were carried out to understand the reaction sequence and the plausible
mechanism.

Introduction. Esters are common functional motifs found in many naturally occurring and
synthetic organic compounds [1]. They are used as bulk chemicals in pharmaceutical and
polymer industries [2]. They are also widely applied in synthetic organic chemistry as versatile
intermediates for further synthetic transformations. Consequently, significant effort has been
devoted over the years for the development of practical and efficient methods for ester synthesis
[3-5]. Esters are usually synthesized via the reaction of acids and their derivatives (acyl chlorides
and anhydrides) with alcohols [3]. Transition metal-catalyzed oxidative esterification of alcohols
or aldehydes has also been developed in the last few years [4,5]. Despite significant advances,
these methods have several drawbacks, such as limited substrate scope, harsh reaction
conditions, and formation of large amounts of unwanted side products. Therefore, development
of new efficient, atom-economic and straightforward alternatives is still desirable.
In this perspective, transition metal catalyzed cross dehydrogenative coupling (CDC) of
carboxylic acids with alkanes under oxidative condition offers an attractive atom-economic one-
pot synthetic approach for the synthesis of a wide variety of esters from various readily available
starting precursors [6]. It allows to avoid the tedious multi-step synthetic procedures such as
preparation of pre-functionalized starting precursors, activated reagents, etc. and thus makes the
synthetic route shorter and more effective.
Over the past decade, much attention has been paid to develop new efficient catalysts and
synthetic methods for C‒C and C‒X (X = N, O, S) bond formation via CDC under oxidative
conditions [6-12]. Several new CDC methods were developed; among them most of the CDC
reactions have been explored for the C‒C bond formation [7]. The examples of carbon-
heteroatom bond formation reactions, however, are still limited. Only in recent years, this
method has been successfully extended for carbon-heteroatom (C‒X, X = N, O, S) bond
formation [8-10]. A few metal-free methodologies were also developed [11].
Despite of several advantages over the other classical synthetic approaches, the CDC
reactions suffers from some severe drawbacks such as poor yield, limited substrate scope and
requirement of expensive noble metal catalysts. Therefore, exploring new catalysts for the
dehydrogenative functionalization of alkanes followed by meticulous investigations of the
reaction steps are desirable to address the current limitations of the CDC reactions.

It is noteworthy to mention that the well-known Kharasch−Sosnovsky reaction involving the
Cu(I)-catalyzed reaction of alkenes with carboxylic acids to form the corresponding allylic ester
is well known since 1957 [13]. We recently reported a new copper(II)-complex containing a
tridentate 2-pyrazol-(1,10-phenanthroline) pincer ligand and studied its application towards
dehydrogenative functionalization of alkanes to esters via oxidative dehydrogenative coupling
with carboxylic acids [12]. Esters were obtained in moderate to good yields from the
dehydrogenative coupling of alkanes and acids in presence of 3.0 equiv. of tert-
butylhydroperoxide (TBHP) and 2.0 mol% of the copper(II)-catalyst in benzene at 80°C. During
this work we realized that the solubility of the copper catalyst plays a key role in the overall
efficiency of the catalytic cycle. We envisioned that a more soluble copper catalyst, preferably
soluble in alkanes, would allow us to avoid the use of carcinogenic benzene as the solvent and be
more effective with low catalyst loading.
Keeping this in mind, we started screening various well-defined copper complexes available
in our laboratory to study dehydrogenative functionalization of alkanes to esters via oxidative
dehydrogenative coupling with carboxylic acids. Among the various available copper catalysts,
the square planar Cu(II)-complex [Cu(MeTAA)] (1) containing a tetraaza macrocyclic ligand
was found to be highly soluble in alkanes and exhibited promising activity in the
dehydrogenative functionalization of alkanes to esters via oxidative CDC of a wide range of
alkanes and carboxylic acids in neat conditions. Various allylic esters were synthesized in
moderate to good yields starting from the corresponding alkanes and acids. A few control
experiments and spectroscopic studies were performed for better understanding of the reaction
sequence and shed light on the plausible mechanism.
Result and Discussion.
Synthesis and Characterization of the Catalyst. The macrocyclic ligand, H2MeTAA
(tetramethyltetraaza[14]annulene) and the Cu(II)-macrocycle complex [Cu(MeTAA)] (1) were
synthesized following known literature methods [14]. Reaction of equimolar amounts of
copper(II)acetate mono-hydrate and H2MeTAA in acetonitrile at 70oC for 0.5 h afforded dark
green colored copper(II)-macrocyclic complex [Cu(MeTAA)] (1). Routine characterization
along with positive-ion ESI mass spectrometry convincingly supports its formulation.

The structure of [Cu(MeTAA)] (1) was confirmed by the single crystal XRD. Slow
evaporation of a dichloromethane-hexane solution of [Cu(MeTAA)] (1) produced single crystals
of the complex. The ORTEP of [Cu(MeTAA)] (1) having ellipsoids at 50% probability level is
displayed in Figure S1. The geometry around the central copper metal is saddle shaped with the
benzene rings and the diiminato chelate rings tilted on opposite sides of the Nitrogen
coordination plane [14c]. To confirm the +2 oxidation state of the central copper ion, low
temperature X-Band EPR and room temperature magnetic moment measurements were carried
out (see SI). A typical axial EPR spectrum along with μeff value of 1.76μB is in complete
agreement with the +2 oxidation state of copper [15].
Dehydrogenative Functionalization of Alkanes to Allylic Esters. To explore the activity of
air-stable [Cu(MeTAA)] (1) towards dehydrogenative functionalization of simple alkanes to
esters via oxidative dehydrogenative coupling with carboxylic acids, the reaction of benzoic acid
(2a) and cyclohexane (3a) were studied under various reaction conditions to obtain the optimal
reaction parameters. The reaction proceeds smoothly in benzene while no desired allylic ester
(4a) was obtained in CHCl3, CH3OH, CH3CN, DMF and DMSO (Table 1, entries 2-6). In
benzene 4a was obtained at a maximum yield of 90% when the dehydrogenative coupling of 2a
and 3a were performed at 80°C in presence of 1.0 mol% catalyst loading and 3.0 equiv. of
TBHP. The catalyst, [Cu(MeTAA)] (1), is highly soluble almost in all organic solvents including
the substrate cyclohexane. Therefore, we decided to explore the catalytic reaction in neat
condition in presence of 3.0 equiv. of TBHP and 1.0 mol% of [Cu(MeTAA)] (1). We were
pleased to find that even in absence of benzene as solvent, the reaction proceeds smoothly and 4a
was obtained in almost identical yields (Table 1, entry 7). Furthermore, in neat conditions, a
catalyst loading of 0.5 mol% is sufficient enough to afford the highest yield (92%) of 4a (Table
1, entry 8). Other available oxidants such as di-tert-butylperoxide (DTBP), O2, H2O2, benzoyl
peroxide [(PhCOO)2] or benzoquinone (BQ) were found to be less effective or ineffective
compared to TBHP (Table 1, entries 8-13). No notable change in the yield of 4a was observed
upon increasing the temperature, reaction time or varying the amounts of TBHP beyond the
optimized conditions. However, the yield of 4a decreased significantly when the reaction was
performed at temperature below 80oC. To further improve the yield of 4a, the reaction of 2a and
3a was carried out in presence of a series of inorganic bases such as K2CO3, Cs2CO3, K3PO4,
MOtBu (M = Li, Na, K), and NaOH respectively (Table 1, entries 14-20). However, the yield of

4a was found to decrease significantly in presence of these bases. In all further catalytic studies
we therefore focused on reactions at 80oC in presence of 0.5 mol% of [Cu(MeTAA)] (1) and 3.0
equiv of TBHP in neat conditions.
To check the background reaction, a few control experiments were carried out under the
optimal reaction parameters (Table 1, entry 8). The coupling of 2a and 3a did not proceed in
absence of [Cu(MeTAA)] (1) or TBHP. Commonly available copper salts like CuCl2, CuI2,
CuCl, CuI, Cu(OAc)2 were found to be less effective, only in presence of Cu(OAc)2 the yield of
4a reached up to 40% [16b]. A 1:1 mixture of H2MeTAA and Cu(OAc)2.H2O was also found to
be less effective affording 4a in only 72% yield (Table 1, entry 22).

Table 1. Screening for optimal reaction conditions of the [Cu(MeTAA)]-catalyzed
dehydrogenative functionalization of alkanes to allylic esters.a-e
(1)
O
[Cu(MeTAA)]
PhCO2H
(2a)
+
TBHP (3.0 equiv.), 80oC,
24 h
Ph
O
(4a)
(3a)
Entry
1
Catalyst(mol%)
[Cu(MeTAA)] (1.0 mol%) Benzene
[Cu(MeTAA)] (1.0 mol%) CHCl3
[Cu(MeTAA)] (1.0 mol%) CH3OH
[Cu(MeTAA)] (1.0 mol%) CH3CN
Solvent
Base
Oxidant Temperature (oC) Yield (%)
-
-
-
-
-
-
-
-
-
-
-
-
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
DTBP
O2
80oC
120oC
80oC
80oC
80oC
80oC
80oC
80oC
80oC
80oC
80oC
80oC
90
0
0
0
0
2
3
4
5
6
7
8
9
[Cu(MeTAA)] (1.0 mol%)
[Cu(MeTAA)] (1.0 mol%)
[Cu(MeTAA)] (1.0 mol%)
[Cu(MeTAA)] (0.5mol%)
[Cu(MeTAA)] (0.5mol%)
[Cu(MeTAA)] (0.5mol%)
[Cu(MeTAA)] (0.5mol%)
[Cu(MeTAA)] (0.5mol%)
DMF
DMSO
Neat
Neat
Neat
Neat
Neat
Neat
0
92
92
80
0
10
11
12
H2O2
0
Benzoyl
peroxide
Trace
13
[Cu(MeTAA)] (0.5mol%)
Neat
-
BQ
80oC
0
14
15
16
17
18
19
20
21
22
[Cu(MeTAA)] (0.5mol%)
[Cu(MeTAA)] (0.5mol%)
[Cu(MeTAA)] (0.5mol%)
[Cu(MeTAA)] (0.5mol%)
[Cu(MeTAA)] (0.5mol%)
[Cu(MeTAA)] (0.5mol%)
[Cu(MeTAA)] (0.5mol%)
CuCl (0.5mol%)
Neat
Neat
Neat
Neat
Neat
Neat
Neat
Neat
Neat
K2CO3
K3PO4
Cs2CO3
LitBuO
NatBuO
KtBuO
NaOH
-
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
80oC
80oC
80oC
80oC
80oC
80oC
80oC
80oC
80oC
10
40
5
30
50
45
40
52
72
[(H2MeTAA) : Cu(OAc)2]
(1:1)
-
b
aIn solvent: PhCO2H (0.5 mmol); cyclohexane (5.0 mmol); TBHP (0.3 mL); Under argon atmosphere. In
neat condition: PhCO2H (0.5 mmol); cyclohexane (10.0 mmol); TBHP (0.3 mL); Under argon atmosphere.
cIn neat condition: PhCO2H (0.5 mmol); cyclohexane (10.0 mmol); base (1.0 equiv.); TBHP (0.3 mL);
e
Under argon atmosphere dBase : 1.0 equiv.; Isolated yields after column chromatography.

With the optimized conditions in hand, we investigated the substrate scope of the present
[Cu(MeTAA)] (1) catalyzed dehydrogenative functionalization of alkanes to esters. A number of
reactions between various (poly)substituted carboxylic acids and alkanes were screened under
the optimal conditions. Table 2 represents the yields of different allylic esters obtained from the
reaction of different substituted benzoic acids (2b-r) with (3a) catalyzed by 1 under our optimal
conditions. The reactions proceeded with benzoic acids containing both electron donating and -
withdrawing functionalities. Irrespective of the positions of the substituents, benzoic acids (2b-j)
containing different electron donating groups produced the respective allylic esters (4b-j) in 85-
95% yield (Table 2, entries 2-10). Carboxylic acids (2l-r) bearing electron-withdrawing
substituents also afforded the corresponding allylic esters (4l-r) in good to moderate yields
(Table 2, entries 12-17). Despite of the strong oxidizing environment, 4-(methylthio)benzoic acid
(2k) still produced 4k in 79% isolated yield (Table 2, entry 11). Using 2-naphthoic acid (2s) and
9-anthracenecarboxylic acid (2t) the desired esters 4s and 4t were obtained in 72 and 68% yields
respectively (Table 2, entry 19, 20). Reactions also proceeded with carboxylic acids containing
heteroaryl rings. For example, 2v and 2w yielded the desired esters 4v and 4w in 87 and 92%
yields respectively (Table 2, entries 22, 23). However, the reaction did not proceed with 2x
(Table 2, entry 24).

Table 2. [Cu(MeTAA)] (1)-catalyzed dehydrogenative functionalization of cyclohexane to
various polysubstituted allylic esters.a,b
(1)
[Cu(MeTAA)]
(0.5 mol%)
O
RCO2H
(2a-2x)
+
TBHP (3.0 equiv.), 80oC,
24 h
R
O
(3a)
(4a-4x)
O
O
O
O
3
O
1
5
2
4
O
O
O
CH3
H3C
CH3
4a (92%)
4c (90%)
4d (88%)
4b (89%)
6
7
8
O
O
CH3 O
O
O
O
H3C
O
O
H3C
H3C
H3C
CH3
OCH3
4h (85%)
CH3
CH3
4f (95%)
4g (87%)
4e (88%)
12
O
O
O
O
O
O
O
9
10
11
O
F
H3CS
H3CO
OPh
4k (79%)
4l (80%)
4i (85%)
4j (85%)
O
O
O
O
14
13
17
O
O
15
16
O
Cl
O
Br
COCH3
Br
4m (82%)
4n(81%)
4o (87%)
4p (83%)
18
20
19
O
O
O
O
O
O
O
O
H3COCO
H3COC
4r (65%)
4q (85%)
4s (72%)
4t (68%)
O
22
21
O
23
24
O
O
O
O
O
O
N
O
S
4u (79%)
4w(92%)
4x (0)
4v (87%)
aIn neat reagents: RCO2H (2a-2x) (0.5 mmol); cyclohexane (3a) (10.0 mmol);
TBHP (0.3 mL, 1.5 mmol); Under argon atmosphere. bIsolated yields after
column chromatography
Next, a few selected aliphatic carboxylic acids (2a'-e') were screened as coupling partners
with 3a to explore the scope and limitation of [Cu(MeTAA)] (1) towards dehydrogenative
synthesis of allylic esters. Cyclohexanecarboxylic acid (2a'), phenylacetic acid (2b'), 2-(2-
fluorophenyl)acetic acid (2c'), 2-phenylbutyric acid (2d') and octanoic acid (2e') were reacted

with 3a under the optimal conditions. Reactions proceeded smoothly with 2a'-d' yielding the
desired allylic esters 5a-5d in 73-78% yields respectively (Table 3, entries 1-4). When long chain
carboxylic acid 2e' was used as the coupling partner, the ester 5e was isolated in only 20% yield
(Table 3, entry 5).
Table 3. [Cu(MeTAA)] (1)-catalyzed dehydrogenative functionalization of cyclohexane to
various polysubstituted allylic esters via dehydrogenative coupling with various aliphatic
carboxylic acids.a,b
(1)
[Cu(MeTAA)]
(0.5 mol%)
O
RCO2H
(2a'-2e')
+
TBHP (3.0 equiv.), 80oC
24 h
R
O
(3a)
2
(5a-5e)
CH3
O
O
F
3
1
5
4
O
O
O
O
O
O
5a (73%)
O
5b (77%)
5c (75%)
5d (78%)
O
5e (20%)
aIn neat reagents: RCO2H (2a'-2e')(0.5 mmol); cyclohexane (3a) (10.0
mmol); TBHP (0.3 mL, 1.5 mmol); Under argon atmosphere. bIsolated
yields after column chromatography
To further check the versatility of the present [Cu(MeTAA)] (1) catalyzed oxidative
dehydrogenative functionalization of alkanes, reactions of 2a with various other cyclic (3b-d)
and acyclic (3e, 3f) alkanes were studied under the optimal reaction parameters. Reactions
proceeded with cyclopentane (3b), cycloheptane (3c) and cyclooctane (3d), however, the
respective esters 6a-c were obtained in 15-20% yield (Table 4, entries 1-3). A slight increase in
yields of 6a-c was observed upon continuing the reaction for 48h. However, no significant
improvement of yields were observed at higher temperature (150°C). The acyclic alkanes 3e and
3f were found to be ineffective yielding the respective products 6d and 6e only in trace quantities
(Table 4, entries 4, 5).

Table 4. [Cu(MeTAA)] (1)-catalyzed dehydrogenative functionalization of various alkanes to
allylic esters via dehydrogenative coupling with benzoic acid.a,b
O
O
n
(1)
[Cu(MeTAA)]
(0.5 mol%)
O
OH
+
n
Benzene, 80oC,TBHP(3.0 equiv.)
24h
(2a)
(3a'-3c')
(6a-6c)
3
3
1
O
O
O
O
O
O
6a (20%)
O
6b(17%)
6c (15%)
O
O
4
5
O
(trace)
(trace)
aIn neat reagents: RCO2H (2a) (0.5 mmol); cycloalkane (3a'-3c') (10.0 mmol);
b
TBHP (0.3 ml, 1.5 mmol); Under argon atmosphere. Isolated yields after
column chromatography
Control Experiments and Mechanistic Investigation. The dehydrogenative functionalization
of alkanes to allylic esters can proceed via either (i) initial formation of the C‒O bond between
the alkane and carboxylic acid followed by dehydrogenation of the in situ formed ester or (ii)
initial dehydrogenation of alkanes to alkenes followed by allylic C–O bond formation [7,9].
Therefore, to investigate the reaction sequence and shed light on the plausible mechanism a few
control experiments were performed.
When the pre-formed cyclohexyl benzoate (3ac) was subjected to dehydrogenation under the
optimal reaction conditions we did not observe any formation of 4a (Scheme 1, entry A). On the
other hand, the reaction of cyclohexene (3ab) with 2a under the optimal reaction conditions
yielded 4a in 90% yields (Scheme 1, entry B). It is worth mentioning that 3a undergoes
dehydrogenation to produce cyclohexene in presence of [Cu(MeTAA)] (1) and TBHP under the
optimal reaction conditions (Scheme 1, entry C). The low yield may be attributed to the highly
reactive nature of the cyclohexenyl radical species, which leads to decomposition or some other
undesired product in absence of any other coupling partner. Both the copper catalyst 1 and TBHP
are essential for the dehydrogenation of cyclohexane to cyclohexene. No cyclohexene formation
was observed in absence of either catalyst 1 or TBHP (Scheme 1, entries D, E). These results are

in agreement with our previous result and available literature which indeed indicates that during
the present [Cu(MeTAA)] (1)-catalyzed dehydrogenative functionalization of alkanes to allylic
esters, dehydrogenation of olefins take place first followed by C‒O bond formation [12].
O
O2CPh
A
(1)
[Cu(MeTAA)]
(0.5 mol%)
O
Benzene, 80oC, TBHP (3.0 equiv.)
24 h
(0%)
4a
(3ac)
(3ab)
( )
O
(1)
[Cu(MeTAA)]
(0.5 mol%)
O
B
C
PhCO2H
(2a)
+
80oC,TBHP (3.0 equiv.)
24 h
(90%)
4a
( )
(1)
[Cu(MeTAA)]
(0.5 mol%)
80oC,TBHP (3.0 equiv.)
24 h
(14%)
(3a)
(3a)
(3a)
(3ab)
TBHP (3.0 equiv.)
80oC, 24 h
D
E
(0%)
(3ab)
(1)
[Cu(MeTAA)]
(0.5 mol%)
80oC, 24 h
(0%)
(3ab)
Scheme 1. Control Experiments to Test the Sequence of C=C and C-O Bond Formation.
To check the involvement of any organic radicals, the reaction of 2a and 3a was performed
in presence of DPPH (2,2-diphenyl-1-picrylhydrazyl). Only a trace amount of 4a was obtained,
indicating the involvement of organic radical intermediates as reported by us and others in
similar dehydrogenative coupling reactions [12]. Moreover, when 3a was subjected to

dehydrogenation in presence of [Cu(MeTAA)] (1), DPPH and TBHP we did not observe any
cyclohexene.
Based on the above experimental data and available literature [16a-f], we propose the
reaction mechanism depicted in Scheme 2. In presence of catalyst, [Cu(MeTAA)] (1) and
carboxylic acids, TBHP undergoes decomposition to the tert-butyloxy radical and the
intermediate [CuIII(MeTAA)(O2CPh)] (1B) is formed. Under thermal conditions, TBHP also
forms tert-butyloxy and tert-butylperoxy radicals, which dehydrogenate the alkanes to the
corresponding alkenes via hydrogen-atom transfer (HAT) followed by a Kharasch−Sosnovsky-
type process [13,16a-f]. This proceeds via HAT from alkanes to form alkanyl radical, which
reacts with the intermediate [CuIII(MeTAA)(O2CPh)] species 1B to form the respective allylic
esters, thus regenerating the Cu(II)-catalyst. The proposed d8 copper(III) intermediate 1B should
be a reactive short-lived species, that either rapidly captures the organic carbon radical directly
or liberates a benzoyl radical with regeneration of Cu(II) upon homolysis of the Cu‒O bond
(followed by rapid C‒O bond formation between the allyl radical and the benzoyl radical). We
cannot fully exclude other reaction mechanisms, such as formation of naked cationic
[CuIII(MeTAA)]+ species via outer sphere SET from Cu(II) to TBHP under the applied reactions
conditions. However, we consider such pathways involving formation of charge-separated
species (of opposite charge) rather unlikely in the applied apolar reaction media.

tBuO
+
tBuOO
2 tBuOOH
H2O
+
PhCO2H
+
tBuOOH
O
O
N
N
N
N
II
Cu
H2O
+
tBuO
(1A)
tBuO
O
O
O
O
HAT
N
N
N
N
N
III
Cu
III
tBuOH
Cu
N
N
N
(1B)
tBuO
HAT
tBuOH
HAT
tBuOO
tBuOOH
Scheme 2. Proposed Mechanism.

Conclusion. In conclusion we have described one pot dehydrogenative functionalization of
alkanes to allylic esters via cross dehydrogenative coupling with carboxylic acids, catalyzed by a
simple, earth abundant Cu(II)-catalyst, [Cu(MeTAA)] (1) under oxidative conditions. The
catalyst, [Cu(MeTAA)] (1) used herein is cheap, easy to prepare, air stable and highly efficient
as the reaction requires only 0.5 mol% catalyst loading. Furthermore, the high solubility of 1
enables us to achieve the catalytic reactions in neat condition, thereby avoiding the use and waste
of solvent. This straightforward methodology is cost-effective and has a wide substrate scope. A
wide range of allylic esters were prepared in moderate to good yields starting from various
affordable and easily available raw materials in neat conditions.
Experimental Section
General Procedures. All the reactions were performed using standard Schlenk techniques under
argon atmosphere. Benzene was refluxed over sodium/benzophenone, distilled under argon
atmosphere, and stored over 4 Å molecular sieves. Methanol, DMF, hexane and CHCl3 were
refluxed with CaH2 and distilled under argon atmosphere. All substituted benzoic acids and
carboxylic acids were obtained from Sigma-Aldrich and TCI. All other reagents were purchased
from commercial suppliers and used as received without further purification. Analytical TLC
was performed on a Merck 60 F254 silica gel plate (0.25 mm thickness) and column
chromatography was performed on Merck 60 silica gel (60-120 mesh). NMR spectra were
recorded on a Bruker DPX-300(300 MHz), Bruker DPX-400(400 MHz) and Bruker DPX-
500(500 MHz) spectrometers. TMS (tetramethylsilane) was used as the internal standard. Room
temperature magnetic moment measurements for [Cu(MeTAA)] was carried out with Gouy
balance (Sherwood Scientific, Cambridge, U.K.). EPR spectra in the X-band were recorded with
a Bruker EMX plus spectrometer.
Synthesis of [Cu(MeTAA)] (1). The free ligand H2MeTAA was synthesized following a known
template synthesis [14c]. [Cu(MeTAA)] was synthesized by directly reacting copper(II) acetate
monohydrate with H2MeTAA in presence of NEt3 as base. In a round-bottom flask, 0.10 g of
copper(II) acetate monohydrate salt (0.60 mmol) and 0.1 g of MeTAA (0.56 mmol) were added
in 4.0 mL acetonitrile. To it 0.20 mL NEt3 was added. Immediately after the addition of NEt3, the
color of the solution turned deep green. The reaction mixture was refluxed for 0.5 h and then
placed in an ice-bath. Deep green microcrystalline complex thus formed was filtered and washed

with
a
small amount of acetonitrile and ether. Fractional crystallization using
dichloromethane/hexane solvent mixture finally yielded the pure complex 1. Yield: 52%.
General Procedures for Dehydrogenative Functionalization of Alkanes to Allylic Esters (in
solvent). Under argon atmosphere, [Cu(MeTAA)] (2.0 mg, 0.005 mmol) and benzoic acid (61
mg, 0.5 mmol) were added in an oven-dried Schlenk tube containing a magnetic stir bar. The
Schlenk tube was evacuated and backfilled with argon (3 cycles). 5.0 mmol cyclohexane (10
equiv), 1.50 mmol (3.0equiv) of TBHP and benzene (1.0 mL) were injected to the Schlenk tube
via syringe. Then the Schlenk tube was placed into an oil bath and heated at 80C for 24 hours.
The reaction was monitored time to time using small TLC plates. After the reaction is complete,
the solvent was evaporated under reduced pressure and the residue was dissolved in
dichloromethane and purified by column chromatography using silica and hexane was used as
eluent.
General Procedures for Dehydrogenative Functionalization of Alkanes to Allylic Esters (in
absence of added solvent). Under an argon atmosphere, [Cu(MeTAA)] (2.0 mg, 0.005 mmol)
and benzoic acid (61 mg, 0.5 mmol) were added in an oven-dried Schlenk tube containing a
magnetic stir bar. The Schlenk tube was evacuated and back filled with argon (3 cycles).
Subsequently 1.50 mmol (3.0 equiv) of TBHP and 1.0 mL cyclohexane were injected to the
Schlenk tube via a syringe. Then the Schlenk tube was placed into an oil bath and heated at 80C
for 24 hours. Once the reaction was completed, the reaction mixture was concentrated in vacuum
and the residue was dissolved in dichloromethane and purified by column chromatography using
silica and hexane was used as eluent.
Control Experiments
To Test the Sequence of C=C and C-O Bond Formation.
(i) Under an argon atmosphere, a mixture of 1 (2.0 mg, 0.005 mmol) and cyclohexyl benzoate
(102 mg, 0.500 mmol) were added in an oven-dried Schlenk tube with a magnetic stir bar. The
schlenk tube was evacuated and backfilled with argon (3 cycles). Then a solution of TBHP (0.3
mL, 1.5 mmol) and benzene (1.0 mL) were injected via a syringe. Since the reactant and the
catalyst were solid, we decided to perform the reaction in benzene solvent. Subsequently, the
Schlenk tube was sealed with Teflon and placed into an oil bath at 80C for 24 hours.

(ii) In an oven-dried Schlenk tube, 1 (2.0 mg, 0.005 mmol) and benzoic acid (61 mg, 0.50 mmol)
were added with a magnetic stir bar. The Schlenk tube was evacuated and back filled with argon
(3 cycles). A solution of cyclohexene (1.0 mL, 10.0 mmol) and TBHP (0.3 mL, 1.5 mmol) were
injected to the Schlenk tube via a syringe. The Schlenk tube was tightly sealed with Teflon and
placed into a preheated oil bath at 80C for 24 hours.
(iii) In an oven-dried schlenk tube, 1 (2.0 mg, 0.005 mmol) was added with a magnetic stir bar.
The schlenk tube was evacuated and backfilled with argon (3 cycles). A solution of cyclohexane
(1.0 mL, 10.0 mmol) and TBHP (0.3 mL, 1.5 mmol) were injected to the Schlenk tube via a
syringe. The Schlenk tube was tightly sealed with Teflon and placed into a preheated oil bath at
80C for 24 hours.
ACKNOWLEDGMENTS. This research was supported by the Council of Scientific &
Industrial Research (CSIR), New Delhi (Project 01(5234)/15), and the Department of Science &
Technology (DST) (Project YSS/2015/001552). R.M. thanks CSIR, G.C. thanks UGC for
fellowship support. X-ray single crystal facility at SAIF, IIESTS is duly acknowledged.
Financial assistance from the IIESTS is acknowledged.
REFERENCES
[1] (a) S. Gryglewicz, W. Piechocki, G. Gryglewicz, Bioresour Technol. 87 (2003) 35–39; (b) J.
P. May, P. Fournier, J. Pellicelli, B. O. Patrick, D. M. Perrin, J. Org. Chem. 70 (2005) 8424-
8430; (c) T. Polat, R. J. Linhardt, Journal of Surfactants and Detergents, vol.4, No. 4 (October
2001).
[2] (a) A. G. A. SA, A. C. de Meneses, P. H. H. de Araújo, D. de Oliveira, Trends in Food
Science & Technology. 69 (2017) 95-105; (b) A. Das, P. Theato, Chem. Rev. 116 (2016)
1434−1495; (c) M. J. O’Donnell, Acc. Chem. Res. 37 (2004) 506-517.
[3] (a) A. Sakakura, K. Kawajiri, T. Ohkubo, Y. Kosugi, K. Ishihara, J. Am. Chem. Soc.
129 (2007) 14775-14779; (b) D. Dev, N. B. Palakurthy, K. Thalluri, J. Chandra, B. Mandal, J.
Org. Chem. 79 (2014) 5420-5431; (c) A. K. Chakraborti, B. Singh, S. V. Chankeshwara, A. R.
Patel, J. Org. Chem.74 (2009) 5967-5974; (d) J. F. Hartwig, J. Am. Chem. Soc. 2016, 138, 2−24.

[4] (a) S. Tang, J. Yuan, c. Liu, A. Lei, Dalton Trans. 43 (2014) 13460-13470; (b) Z. Shi , C.
Zhang , C. Tang, N. Jiao, Chem. Soc. Rev. 41 (2012) 3381-3430; (c) S. Gowrisankar, H.
Neumann, M. Beller, Angew. Chem. Int. Ed. 50 (2011) 5139 –5143.
[5] (a) R. Gopinath, B. K. Patel, Org. Lett. 2 (2000) 577-579; (b) C. Liu, S. Tang, L. Zheng, D.
Liu, H. Zhang, A. Lei, Angew. Chem. Int. Ed. 51 (2012) 5662 –5666; (c) R. S. Reddy, J. N.
Rosa, L. F. Veiros , S. Caddick, P. M. P. Gois, Org. Biomol. Chem. 9 (2011) 3126-3129; (d) R.
Lerebours, C. Wolf, J. Am. Chem. Soc. 128 (2006) 13052-13053.
[6] (a) H-H. Wang, W-H. Wen, H-B. Zou, F. Cheng, A. Ali, L. Shi, H-Y. Liu, C-K. Chang, New
J. Chem. 41 (2017) 3508-3514; (b) G. Majji, S. K. Rout, S. Rajamanickam, S. Guin, B. K. Patel,
Org. Biomol. Chem. 14 (2016) 8178–8211; (c) M-F. Xiong, A. Ali, W. Akram, H. Zhang, L-P.
Si, H-Y. Liu, DOI: 10.1016/j.catcom.2019.04.001.
[7] (a) C.-J. Li, Acc. Chem. Res. 42 (2009) 335–344; (b) Z. Li, D. S. Bohle, C.-J. Li, Proc. Natl.
Acad. Sci. USA. 103 (2006) 8928–8933; (c) S. A. Girard, T. Knauber, C.-J. Li, Angew. Chem.
Int. Ed. 53 (2014) 74–100; (d) Z. Xie, Y. Cai, H. Hu, C. Lin, J. Jiang, Z. Chen, L. Wang, Y. Pan,
Org. Lett. 15 (2013) 4600–4603; (e) Z. Li, C-J. Li, J. Am. Chem. Soc. 128 (2006) 56–57; (f) S.
Guin, S. K. Rout, A. Banerjee, S. Nandi, B. K. Patel, Org. Lett. 14 (2012) 5294–5297; (g) P.
Wang, H. Rao, R. Hua, C-J. Li, Org. Lett. 14 (2012) 902-905.
[8] (a) H. Aruri, U. Singh, M. Kumar, S. Sharma, S. Aithagani, K. V. K. Gupta, S. Mignani, R.
A. Vishwakarma, P. P. Singh, J. Org. Chem. 82 (2017) 82 1000–1012; (b) Y. Zhao, B. Huang,
C. Yang, W. Xia, Org. Lett. 18 (2016) 3326–3329; (c) S. Rajamanickam, G. Majji, S. K. Santra,
B. K. Patel, Org. Lett. 17 (2015) 5586–5589; (d) F. Yang, J. Li, J. Xie, Z. Huang, Org. Lett.
(2010) 5214-5217; (e) Z-l. Li, L-k. Jin, C. Cai, Org. Biomol. Chem. 15 (2017) 1317.
[9] (a) S. Guin, S. K. Rout, A. Banerjee, S. Nandi, B. K. Patel, Org. Lett. 14 (2012) 5294-5297;
(b) J. Lan, H. Xie, X. Lu, Y. Deng, H. Jiang, W. Zeng, Org. Lett. 19 (2017) 4279−4282; (c) L.
Chen, E. Shi, Z. Liu, S. Chen, W. Wei, H. Li, K. Xu, X. Wan, Chem. Eur. J. 17 (2011) 4085 –
4089.
[10] (a) Q. Chen, X. Wang, C. Wen, Y.Huang, X. Yan, J. Zeng , Rsc Adv. 7 (2017) 39758-39761;
(b) S. Song, Y. Zhang, A. Yeerlan, B. Zhu, J. Liu, N. Jiao, Angew.Chem.Int.Ed. 56 (2017) 2487–
2491; (c) X. Huang, Y. Chen, S. Zhen, L. Song, M. Gao, P. Zhang, H. Li, B. Yuan, G. Yang, J.
Org. Chem. DOI: 10.1021/acs.joc.7b02718.

[11] (a) Y. Zhang, C-J. Li, J. Am. Chem. Soc. 128 (2006) 4242-4243; (b) G. Majji, S. Guin, A.
Gogoi, S. K. Rout, B. K. Patel, Chem. Commun. 49 (2013) 3031; (c) T. Xiao, L. Li, G. Lin, Z-w.
Mao, L. Zhou, Org. Lett. 16 (2014) 4232−4235; (d) X. Kang, R. Yan, G. Yu, X. Pang, X. Liu, X.
Li, L. Xiang, G. Huang, J. Org. Chem. 79 (2014) 10605−10610.
[12] U. Jash, G. Chakraborty, S. Sinha, R. Sikari, R. Mondal, N. D. Paul, A. J. Org. Chem. 7
(2018) 1681-1688.
[13] M. S. Kharasch, G. Sosnovsky, J. Am. Chem. Soc. 80 (1958) 756.
[14] (a) S. Parua, S. Das, R. Sikari, S. Sinha, N. D. Paul, J. Org. Chem. 82 (2017) 7165–7175;
(b) A. Chirila, B. G. Das, N. D. Paul, B. de Bruin, ChemCatChem. 9 (2017) 1413–1421; (c) G.
Ricciardi, A. Bavoso, A. Rosa, F. Lelj, Y. Cizovb, J. Chem. Soc. Dalton Trans. 14 (1995) 2385–
2389; (d) S. Parua, R. Sikari, S. Sinha, S. Das, G. Chakraborty, Paul, N. D. Org. Biomol.
Chem. 16 (2018) 274-284. (e) S. Parua, R. Sikari, S. Sinha, G. Chakraborty, R. Mondal, N. D.
Paul, J. Org. Chem. 83 (2018) 11154-11166.
[15] (a) M. F. Ottaviani, S. Bossmann, N. J. Turro, D. A. Tomalia, J. Am. Chem. Soc. 116
(1994) 661-671; (b) P. Comba, T. W. Hambley, M. A. Hitchman, H. Stratemeier, Inorg. Chem.
34 (1995) 3903-3911.
[16] (a) S. K. Rout, S. Guin, W. Ali, A. Gogoi, B. K. Patel, Org. Lett. 16 (2014) 3086–3089; (b)
S. K. Rout, S. Guin, K. K. Ghara, A. Banerjee, B. K. Patel, Org. Lett. 14 (2012) 3982; (c) J.
Zhao, H. Fang, W. Zhou, J. Han, Y. Pan, J. Org. Chem. 79 (2014) 3847–3855; (d) J. Zhao, H.
Fang, J. Han, Y. Pan, Org. Lett. 16 (2014) 2530–2533; (e) Z.-Q. Liu, L. Zhao, X. Shang, Z. Cui,
Org. Lett. 14 (2012) 3218–3221; (f) B. L. Tran, M. Driess, J. F. Hartwig, J. Am. Chem. Soc. 136
(2014) 17292–17301; (g) H. Yi, G. Zhang, H. Wang, Z. Huang, J. Wang, A. K. Singh, A. Lei,
Chem. Rev. 117 (2016) 9016–9085; (h) D. Talukdar, S. Borah, M. K. Chaudhuri , Tetrahedron
Letters 56 (2015) 2555–2558; (i) J. Cao, L‐W. Xu, Solvents as Reagents in Organic Synthesis:
Reactions and Applications, Chapter 11: Synchronous Application of Hydrocarbons as Solvents
and Reagents in Transition‐Metal Catalysis; (j) C-S. Wang, T. Roisnel, P. H. Dixneuf, J-F.
Soule, Org. Lett. 19 (2017) 6720–6723; (k) Y. Li, C. Wang, F. Zhu, Z. Wang, P. H. Dixneuf, X-
F. Wu, ChemSusChem 10 (2017) 1341–1345; (l) C. Zhang, P. Feng, N. Jiao, J. Am. Chem. Soc.
135 (2013) 15257–15262.

There are no conflicts to declare.

C-H Functionalization • Cross Dehydrogenative Coupling • Cu-catalyst • Organic Radical •
Allylic Esters