Nickel-catalyzed oxidative esterification of formamides with 1,3-dicarbonyl compounds under mild reaction conditions

Article abstract of DOI:10.1002/aoc.3855

Synthesis of enol carbamates was achieved via nickel-catalyzed oxidative coupling of formamides with 1,3-dicarbonyl compounds in the presence of tert-butyl hydroperoxide at 40?°C. Various derivatives of enol carbamates were synthesized by this method in good to excellent yields.

Full text of DOI:10.1002/aoc.3855

Received: 9 November 2016
DOI: 10.1002/aoc.3855
Revised: 18 March 2017
Accepted: 25 March 2017
C O M M U N I C A T I O N
Nickel‐catalyzed oxidative esterification of formamides with
1,3‐dicarbonyl compounds under mild reaction conditions
Dariush Saberi1
| Samira Poorsadeghi2
1 Fisheries and Aquaculture Department,
College of Agriculture and Natural
Resources, Persian Gulf University, Bushehr
75169, Iran
2 Chemistry Department, Tarbiat Modares
University, P.O. Box 14155‐4838, Tehran,
Iran
Synthesis of enol carbamates was achieved via nickel‐catalyzed oxidative coupling
of formamides with 1,3‐dicarbonyl compounds in the presence of tert‐butyl
hydroperoxide at 40 °C. Various derivatives of enol carbamates were synthesized
by this method in good to excellent yields.
KEYWORDS
Correspondence
1,3‐Dicarbonyls, enol carbamates, nickel, oxidative coupling, TBHP
Dariush Saberi, Fisheries and Aquaculture
Department, College of Agriculture and
Natural Resources, Persian Gulf University,
Bushehr 75169, Iran.
Email: saberi_d@pgu.ac.ir
Funding information
Iran National Science Foundation (INSF),
Grant/Award Number: 94015753
1 | INTRODUCTION
carbamates via the oxidative coupling of formamides with
β‐dicarbonyl compounds or ortho‐substituted phenolic com-
Carbamates are important motifs due to their pharmacologi-
cal properties such as antibiotic, fungicide, insecticide, and
herbicide.[1] Moreover, they are considered as significant
synthetic intermediates and protecting groups in chemical
industry.[2]
Traditionally, synthesis of these compounds is performed
via the reaction of amines with phosgene or its derivatives,
such as chloroformate,[3] dialkyl carbonates[4] or the reaction
of alcohols with isocyanates.[5] However, regarding the
toxicity of these reagents and the generation of various
by‐products, there is still room for the development of
alternative methods.
Lately, cross‐dehydrogenative coupling (CDC) has
enhanced the efficiency of synthetic procedures leading to
C‐O bond formation.[6] These reactions enable one to synthe-
size molecules via shorter reaction routes and with higher
atom‐economy.[7]
pounds.[8] They performed these reactions in the presence
of copper salts (CuCl2 or Cu(OAc)2) as the catalyst and
TBHP as the oxidant at 80 °C (Scheme 1, Equation 1).
Subsequently, Chang et al. conducted these reactions by
employment of CuCl/TBHP system at 70 °C which
resulted in the same products with excellent yields in a
much shorter reaction time.[9] Moreover, copper‐catalyzed
oxidative coupling of formamides with salicylaldehydes
has already been reported for the synthesis of carbamates
(Scheme 1, Equation 2).[10]
Nickel, in its elemental form, has lower price than its
d10‐block counterparts. Different oxidation states and small
atomic radius which lead to short Ni–ligand bond lengths
are among other distinctive features of nickel which justify
its versatility.[11] Moreover, in contrast to palladium, facile
accessibility of Ni(I) and Ni(III) oxidation states allows
radical mechanisms in its reactions.[11] All these attributes
Copper‐catalyzed CDC reaction of formamides with
suitable precursors for the synthesis of carbamates has been
well studied. In 2011, Reddy et al. reported the synthesis
of enol carbamates and 2‐carbonyl‐substituted phenol
make Ni a common catalyst in the area of cross‐coupling
[12]
reactions.
In this line of research, we have found that
NiCl2, a cheap and readily available salt, can be an effec-
tive substitute for copper in the synthesis of carbamates,
Appl Organometal Chem. 2017;e3855.
wileyonlinelibrary.com/journal/aoc
Copyright © 2017 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.3855

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SABERI AND POORSADEGHI
SCHEME 1 Different conditions for
synthesis of carbamates via CDC reactions
TABLE 1 Screening optimum conditionsa
Entry
Catalyst (10 mol%)
Oxidant (mmol)
Temp (°C)
Yield (%)b
1
NiCl2.6H2O
Ni(OAc)2.2H2O
Ni(NO3)2.6H2O
NiSO4.6H2O
FeCl2.4H2O
RuCl3.xH2O
MnCl2.4H2O
NiCl2.6H2O
NiCl2.6H2O
NiCl2.6H2O
NiCl2.6H2O
NiCl2.6H2O
NiCl2.6H2O
NiCl2.6H2O
NiCl2.6H2O
NiCl2.6H2O
NiCl2.6H2Oc
NiCl2.6H2Od
‐
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)
DTBP (2)
mCPBA (2)
H2O2 (2)
NaOCl (2)
Can (2)
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
40
50
0
2
3
0
4
0
5
0
6
0
7
0
8
0
9
0
10
11
12
13
14
15
16
17
18
19
20
0
0
0
TBHP (4)
TBHP (6)
TBHP (4)
TBHP (4)
TBHP (4)
TBHP (4)
TBHP (4)
‐
70
70
90
85
90
50
0
80
40
40
40
NiCl2.6H2O
40
0
c
aReaction conditions: 1a (1 mmol), 2a (2 ml), 40 °C, 5 h, under air atmosphere. bIsolated yield; 20 mol% of catalyst was used; d5 mol% of catalyst was used.

SABERI AND POORSADEGHI
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since it has the aptitude to promote this reaction under
milder conditions (Scheme 1, Equation 3).
Bruker Avance (DRX 300,400, or 500 MHz) in pure deu-
terated CDCl3 solvent with tetramethylsilane (TMS) as
internal standard.
2 | EXPERIMENTAL SECTION
2.2 | General procedure for synthesis of
carbamates (3a–r and 5a, 5b):
2.1 | Chemicals, instrumentation and analysis
All reagents were purchased from commercial suppliers
and used without further purification. Progress of reac-
tions was monitored by thin layer chromatography while
purification was effected by column chromatography,
using silica gel (Merck 230–240 mesh). FT‐IR spectra
were obtained over the region 400–4000 cm−1 with
NICOLET IR100 FT‐IR with spectroscopic‐grade KBr.
1H–NMR and 13C–NMR spectra were recorded on a
TBHP (70 wt% in water, 4 equiv) was added dropwise,
with stirring over a period of 5 minutes, to a mixture of
1,3‐dicarbonyl compound or 2‐hydroxyacetophenone
(1 mmol), NiCl2.6H2O (24 mg, 10 mol%) and formamide
(2 ml) at 40 °C. After stirring for five hours, water
(10 ml) was added and then the reaction mixture was
extracted with ethyl acetate (3 × 10 ml) and dried over
anhydrous Na2SO4. Removal of the solvent under vacuum
afforded the crude product which was purified by column
chromatography on silica gel (eluent: n‐hexane‐ethyl ace-
tate 5: 1) to afford the desired product.
2.2.1 | General procedure for the esterification
of 1,3‐dicarbonyl compounds or 2‐hydroxy
acetophenone (7a–e and 8a–c)
TBHP (70 wt% in water, 4 equiv) was added dropwise, with
stirring over a period of 5 min, to a mixture of 1,3‐dicarbonyl
compound or 2‐hydroxyacetophenone (1 mmol), aldehyde
(1.2 mmol), NiCl2.6H2O (24 mg, 10 mol%) and DMSO
(2 ml) at 40 °C. After stirring for ten hours, water (10 ml)
was added and then the reaction mixture was extracted with
ethyl acetate (3 × 10 ml) and dried over anhydrous Na2SO4.
Removal of the solvent under vacuum afforded the crude
product which was purified by column chromatography on
silica gel (eluent: n‐hexane‐ethyl acetate 5: 1) to afford the
desired product.
All the synthesized products were known and character-
ized by comparing spectral data with those of previously
reported (see Supporting Information).[8–10,13]
3 | RESULTS AND DISCUSSION
To explore optimum conditions, the reaction of ethyl
acetoacetate and DMF was selected as the model reaction.
The first reaction was performed under the following
conditions: ethyl acetoacetate (1 mmol), DMF (2 ml),
TBHP (2 equiv.) as the oxidant, NiCl2.6H2O (10 mol%)
as the catalyst at room temperature. Under these conditions,
enol carbamate 3a was obtained in 50% yield (Table 1,
entry 1). Other Ni salts such as Ni(OAc)2.2H2O,
Ni(NO3)2.6H2O, and NiSO4.6H2O failed to promote this
transformation (Table 1, entries 2–4). Further investigation
revealed that attempts to achieve the desired product by
the use of chloride salts of Fe, Ru, and Mn were futile
FIGURE
1
Substrate scope. Reaction conditions: β‐diketone
(1 mmol), TBHP (4 mmol), NiCl2.6H2O (10 mol%), 40 °C, reaction
time: 5 h; the yields refer to the isolated pure products

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SABERI AND POORSADEGHI
SCHEME 2 Oxidative esterification of
2‐hydroxyacetophenone with formamides
SCHEME 3 Oxidative esterification of
aldehydes with β‐diketones or
2‐hydroxyacetophenone. Values in pranteses
refer to perform the reactions at 80 °C
(Table 1, entries 5–7). Next, the effect of oxidants on the
yield of the product was taken into account. With this
aim in mind, the reaction was carried out in the presence
of several oxidizing reagents, such as DTBP, mCPBA,
H2O2, NaOCl, and CAN, but in neither case was carbamate
formed (Table 1, entries 8–12). Fortunately, when the
amount of the oxidant increased up to 4 equivalents, the
yield was raised to 70% (Table 1, entry 13). However, fur-
ther build‐up of the oxidant amount brought about a negli-
gible change in the yield (Table 1, entry 14). In the next
step, we investigated the temperature influence. To this
end, the temperature rose to 40 °C which improved the
reaction efficiency (Table 1, entry 15), but additional
increase in the temperature led to a drop of yield
(Table 1, entry 16). Then, we conducted the reaction in
the presence of 20 mol% of the catalyst under which the
yield remained almost unchanged, while reducing its
amount to 5 mol%, decreased the efficiency to 50%
(Table 1, entries 17 and 18). It is also noteworthy that in
the absence of the catalyst or the oxidant, no product was
formed (Table 1, entries 19 and 20) assuring that their
presence is crucial for promotion of this reaction.
SCHEME 4 Unsuccessful esterification of propiophenone with DMF
After optimization, in order to extend the scope of
this reaction, a wide range of 1,3‐dicarbonyl compounds
were reacted with N,N‐dialkyl formamides under optimum
conditions which in most cases furnished the desired enol
carbamates in high yields. The results are shown in
Figure 1. In accordance with the previously reported
SCHEME 5 Proposed mechanism
results, the nature of the 1,3‐dicarbonyl compounds and
dialkyl formamides did not have any significant influence
on the reactivity. It should be noted that the reason

SABERI AND POORSADEGHI
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behind the lower yield of 1,3‐cyclohexadione carbamates
(3q and 3r) is perhaps due to the lack of binding capac-
ity of cyclic β‐diketones to the metal in a bidentate
fashion.[9]
experiments showed that the coordination of dicarbonyl
compounds with Nickel played an important role in the
reaction mechanism.
Encouraged by these results, we then replaced
β‐dicarbonyls with 2‐hydroxyacetophenone 4 which has
structural similarities to the enol tautomer of the diketone
moiety. To our delight, when reacted with dialkylformamides,
the corresponding carbamates were obtained in acceptable
yields under the same conditions (Scheme 2).
ACKNOWLEDGEMENTS
The authors express their gratitude to the research council of
Iran National Science Foundation (INSF), Grant 94015753
for financial support during the course of this review.
In another attempt, the reaction of aldehydes with
β‐diketones or 2‐hydroxyacetophenone, which has already
been conducted by a copper catalyst,[13] was investigated in
which Ni proved to be gratifyingly efficacious. Also, when
the temperature rose to 80 °C even better results were
obtained. (Scheme 3).
Although the exact reaction mechanism still remains
unclear, the reaction may proceed in a similar mode to
Cu‐catalyzed esterification as previously reported.[8–10,13,14]
The reaction was completely suppressed when 1.5 equiv. of
TEMPO was added to the model reaction confirming that it
proceeded through a radical pathway. As has already been
taken into consideration,[15] dicarbonyl compounds have an
aptitude to coordinate metals and set the scene for
implementation of this reaction. To support this hypothesis,
when the propiophenone was subjected to the reaction
conditions, the product 3 s was not formed (Scheme 4). This
indicates the importance of the adjacent carbonyl group for
carbamate formation.
Accordingly, we proposed a mechanism which is
depicted in Scheme 5. Presumably, at the first stage complex
(A) is formed through the reaction of β–dicarbonyl with the
nickel salt. Treatment of this complex with TBHP produces
complex (B) and a tert‐butoxyl radical. Tert‐Butoxyl radical
then abstracts a hydrogen radical from formamide giving rise
to the corresponding radical. This radical, then, reacts with
nickel complex (B) affording the desired carbamate and
Ni(II) chloride which returns to the catalytic cycle.
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4 | CONCLUSIONS
In conclusion, we have described the first example of a Ni‐
catalyzed oxidative esterification of 1,3‐dicarbonyl com-
pounds or 2‐hydroxyacetophenone with formamides toward
the synthesis of enol carbamates with TBHP as an environ-
mentally benign oxidant. NiCl2, as a cheap and readily avail-
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effectively under mild reaction conditions. Various enol
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SUPPORTING INFORMATION
Additional Supporting Information may be found online in
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How to cite this article: Saberi D, Poorsadeghi S.
Nickel‐catalyzed oxidative esterification of
formamides with 1,3‐dicarbonyl compounds under
mild reaction conditions. Appl Organometal Chem.
2017;e3855. https://doi.org/10.1002/aoc.3855
[14] a) D. Saberi, A. Heydari, Tetrahedron Lett. 2013, 54, 4178; b) D.
Saberi, S. Mansoori, E. Ghaderi, K. Niknam, Tetrahedron Lett.
2016, 57, 95.
[15] a) C. He, G. Zhang, J. Ke, H. Zhang, J. T. Miller, A. J. Kropf, A.
Lei, J. Am. Chem. Soc. 2013, 135, 488; b) F. Monnier, F. Turtaut,