nBu4NI-catalyzed oxidative cross-coupling of carbon dioxide, amines, and aryl ketones: access to O-β-oxoalkyl carbamates

Article abstract of DOI:10.1039/c6cc09762f

The first nBu₄NI-catalyzed oxidative cross-coupling reaction of carbon dioxide, amines and arylketones has been successfully developed by using TBHP as the oxidant, providing an efficient, atom-economical and metal-free strategy for the synthesis of a range of O-β-oxoalkyl carbamates.

Full text of DOI:10.1039/c6cc09762f

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Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc
first methanofullerene derivatives of Sc
3
N@C2n (2n
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DOI: 10.1039/C6CC09762F
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nBu NI-catalyzed oxidative cross-coupling of carbon dioxide,
4
amines, and aryl ketones: access to O-β-oxoalkyl carbamates
Received 00th January 20xx,
Accepted 00th January 20xx
a†
b†
a
b
b
b
Youbin Peng, Juan Liu, Chaorong Qi,* Gaoqing Yuan,* Jiawei Li, and Huanfeng Jiang
DOI: 10.1039/x0xx00000x
www.rsc.org/
The first nBu NI-catalyzed oxidative cross-coupling reaction of facile and atom-economical methods for the construction of
4
carbon dioxide, amines and arylketones has been successfully carbamates is still highly desirable.
developed by using TBHP as the oxidant, providing an efficient,
atom-economical and metal-free strategy for the synthesis of a
range of O-β-oxoalkyl carbamates.
Organic carbamates are compounds of great interest because
1
2
they are key units of many natural products, pharmaceuticals
3
and agrochemicals (Figure 1). They also find increasing
applications in organic synthesis as versatile building blocks or
protecting groups for amines and amino acids.
4
Traditionally, these important compounds can be prepared
by the reaction of chloroformates with amines or the reaction
5
of isocyanates with alcohols. However, both chloroformates
and isocyanates are commonly obtained from highly toxic Figure 1 Representative carbamate-bearing molecules.
phosgene. To address the environmental and safe issues
associated with the use of phosgene, great efforts have been
made to develop new and environmentally friendly methods
6
for the synthesis of carbamates in the past decades. Of
particular note is the carbamation of amines using carbon dioxide
7
(
CO ) as the raw material since CO is inarguably regarded as a
2
2
8
non-toxic, abundant, inexpensive and renewable C1 resource.
Basically, these transformations rely on the in situ generation of
carbamate anion via the reaction of amines and CO , followed by
2
the reaction with electrophiles (Scheme 1, a). A variety of functional
7b, 7d, 7f
7e, 7g, 7i
molecules, such as halohydrocarbons
and alcohols,
have been employed as the electrophile. Very recently, we have
9
a
9b
showed that N-tosylhydrazones and diaryliodonium salts could
couple with CO2 and amines to give the corresponding organic
carbamates in the presence of bases. Although significant progress
has been made in this research area, the development of more
a
School of Chemistry and Chemical Engineering, State Key Lab of Luminescent
Materials and Devices, South China University of Technology, Guangzhou 510640,
P. R. China. E-mail: crqi@scut.edu.cn
Key Lab of Functional Molecular Engineering of Guangdong Province, School of
b
Chemistry and Chemical Engineering, South China University of Technology,
Guangzhou 510640, P. R. China. E-mail: gqyuan@scut.edu.cn
†
These authors contributed equally to this work.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
2
Scheme 1 Strategies for the synthesis of organic carbamates from CO .
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Journal Name
Over the past decades, catalytic functionalization of C-H efficiently to furnish 3aa in high yields (entries 6-9) while CuI
View Article Online
exhibited exceedingly low catalytic
Moreover, the reaction did not occur when nBu NBr was used
D
a
O
c
I
t
:
i
1
v
0
i
.
t
1
y
4
039
(
/
e
C
n
6
t
C
r
C
y
097
10).
6
2
F
bonds has become one of the most efficient strategies in
organic synthesis because it avoids the requirement for
prefunctionalization of substrates and thus shows improved
atom- and step-economy. However, to the best of our
knowledge, the direct assembly of organic carbamates via C-H
functionalization has not yet been developed. As part of our
as the catalyst (entries 11 and 12), implying that the use of
iodides or iodine was critical for the reaction. Screening of
different oxidants showed that the oxidant play an important
role in this transformation. TBHP was the optimal oxidant;
other oxidants, such as DTBP, TBPB, BPO and H O , were
1
0
2
2
ongoing interest in developing efficient methods for the
ineffective (entries 13-16). Both increasing and decreasing the
reaction temperature decreased the yield of 3aa (entries 17
9
conversion of CO into valuable chemicals, herein, we wish to
2
report a nBu NI-catalyzed direct α-carbamoyloxylation of and 18). Further optimization showed that a decrease in the
4
3
arylketones with CO and amines via C(sp )-H oxidative cross- pressure of CO
resulted in a decrease in the yield of the
2
2
coupling reactions, providing an efficient, atom-economical product (entry 19). The effect of the amount of oxidant and 2a
on the reaction was investigated, and the results showed that
equiv of TBHP and 7 equiv of 2a were required to achieve
high yield (see the Supporting Information for details). Finally,
and metal-free protocol for the synthesis of a diverse range of
O-β-oxoalkyl carbamates (Scheme 1, b).
Initially, propiophenone (1a) and diethylamine (2a) was
chosen as the model substrates for the optimization of the
reaction conditions, and the results are summarized in Table 1.
6
the control experiments showed that both nBu NI and TBHP
4
are essential for the transformation (entries 20 and 21).
To examine the scope and limitations of the present
carbamoyloxylation, a variety of aryl and heteroaryl ketones
When the reaction was carried out in DMF with nBu NI as
4
o
catalyst and TBHP as the oxidant under 3 MPa of CO at 90 C
2
were examined as substrates to react with CO and 2a under
2
for 12 h, the desired product 3aa was formed in 77% yield
(
the optimized reaction conditions (Scheme 2). Gratifyingly,
entry 1). DMSO also gave 3aa in 60% yield while other various propiophenone derivatives bearing electron-donating
solvents such as CH CN and DCE led to relatively low yields
3
(entries 2, 4 and 5). Pleasingly, the yield of 3aa was sharply
increased to 92% when the reaction was conducted in a mixed
DMF-DMSO (2:1) solvent (entry 3), which might be due to that
the mixed solvent system could facilitate the formation of
active intermediates of the reaction. Other iodides including KI,
NH I, NIS, and even I could also catalyse the reaction
4
2
a
Table 1 Optimization of the reaction
b
Entry
Catalyst
Oxidant
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
Solvent (v:v)
DMF
DMSO
DMF/DMSO (2:1)
Yield (%)
77
60
92 (87)
1
2
3
4
5
6
7
8
9
nBu
nBu
nBu
nBu
nBu
4
NI
4
NI
4
NI
4
NI
4
NI
CH CN
3
32
9
86
85
83
78
10
n.d.
n.d.
n.d.
trace
n.d.
n.d.
76
73
46
n.d.
n.d.
DCE
KI
NH
NIS
DMF/DMSO (2:1)
DMF/DMSO (2:1)
DMF/DMSO (2:1)
DMF/DMSO (2:1)
DMF/DMSO (2:1)
DMF/DMSO (2:1)
DMF/DMSO (2:1)
DMF/DMSO (2:1)
DMF/DMSO (2:1)
DMF/DMSO (2:1)
DMF/DMSO (2:1)
DMF/DMSO (2:1)
DMF/DMSO (2:1)
DMF/DMSO (2:1)
DMF/DMSO (2:1)
DMF/DMSO (2:1)
4
I
I
2
1
1
1
1
1
1
1
0
1
2
3
4
5
6
CuI
nBu
nBu
4
NBr
NBr
4
2 2 8
K S O
nBu
nBu
nBu
nBu
nBu
nBu
nBu
-
4
NI
4
NI
4
NI
4
NI
4
NI
4
NI
4
NI
DTBP
TBPB
BPO
2 2
H O
c
1
7
TBHP
TBHP
TBHP
TBHP
-
d
e
1
1
8
9
2
2
0
1
nBu
4
NI
a
Reaction conditions: 1a (1.0 mmol), 2a (7.0 mmol), CO
2
o
(3 MPa),
b
nBu
4
NI (0.2 mmol), TBHP (6.0 mmol), solvent (3 mL), 90 C, 12 h.
Scheme
conditions:
mmol), DMF/DMSO (v:v = 2:1, 3 mL), CO
yields based on
2
Substrate scope with respect to ketones. Reaction
(1.0 mmol), 2a (7.0 mmol), nBu NI (0.2 mmol), TBHP (6.0
(3 MPa), 90 C, 12 h. Isolated
Yields were determined by GC-MS analysis with n-dodecane as internal
c
1
4
standard; number in parentheses is the yield of isolated product. At
o
o
d
o
e
2
1
2
10 C. At 70 C. Under 1 MPa of CO .
1
.
2
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or electron-withdrawing groups at the ortho, meta, or para Pleasingly, different dialkylamines, including symViemw eArttircilce Oannlinde
positions of the benzene ring, including methyl, methoxy, asymmetric ones, underwent the one-p ly
D
o
O
t
I:
r
1
e
0
a
.1
c
0
t
3
io9/
n
C6
s
C
m
C
o
0
o
9762F
t
h
trifluoromethyl, halide (F, Cl and Br) and nitro groups, could and furnished the corresponding products (3ab-3ai) in
undergo the reaction smoothly to give the desired products moderate to excellent yield. Moreover, various types of cyclic
(
3ba-3ja) in moderate to high yields. It was found that the secondary amines could also take part in the reaction, giving
electronic nature of the substituents has a great effect on the rise to the desired products in moderate to good yield (3aj-
formation of the desired carbamates. In general, ketones with 3ao). The structure of the product 3an was unambiguously
12
electron-withdrawing groups generated the desired products confirmed by means of X-ray crystallographic analysis.
3da 3ja) in higher yields than those with electron-donating Unfortunately, primary amines and anilines could not afford
(
-
ones (3ba and 3ca). Besides mono-substitued propiophenones, the desired products but resulted in the formation of a
the di-substituted substrate, 1-(2,4-dichlorophenyl)propan-1- complex mixture of unidentified products under our conditions.
one (3k) could also work well to furnish the expected product
To understand the mechanism of the reaction, a series of
3
ka in 82% yield. Notably, a variety of heteroaryl ketones control experiments were carried out as shown in Scheme 4.
containing the furan, thiophene and pyridine rings were all Firstly, it was found that the present reaction could be
suitable substrates for the transformation, delivering the inhibited by the radical scavengers 2,2,6,6-teramethyl-1-
desired products (3la
substrates with longer alkyl chains (1o and 1p) reacted (BHT) (Scheme 4, a and b). Moreover, diphenylcyclopropyl
smoothly to afford the corresponding products 3oa and 3pa in ketone could undergo ring-opening radical clock reaction
good yields. 1,2-Diphenylethanone could also enter into the under the standard conditions to afford the conjugated diene
-3na) in good yields. Moreover, the piperidinyloxy (TEMPO) and 2,6-di-tert-butyl-4-methylphenol
4
1
3
reaction to give the desired carbamate 3qa in a moderated
yield. Interestingly, 3-chloro-1-phenylpropan-1-one 1r
5
in 62% NMR yield (Scheme 4, c). These results suggest that
(
)
a radical pathway should be involved in the reaction. Next,
generated an unsaturated carbamate 3ra, which might be when 2-hydroxy-1-phenylpropan-1-one was employed as
formed through the dehydrohalogenation of the desired substrate to react with CO2 and diethylamine under the
11
product. However, the reaction of acetophenone gave a standard conditions, no product 3aa was detected (Scheme 4,
complex mixture, and the desired product was not detected. d). However, the reaction of 2-iodo-phenylpropan-1-one with
Aliphatic ketones also failed to undergo the reaction, and the CO and diethylamine could furnish the carbamate 3aa in 83%
2
starting materials were recovered unchanged.
Subsequently, a wide range of amines were employed for might be the intermediate for the reaction.
coupling with propiophenone 1a) and CO2 (Scheme 3).
yield (Scheme 4, e), indicating that 2-iodo-phenylpropan-1-one
(
Scheme 4 Mechanism studies.
On the basis of aforementioned observations and previous
7
, 9a, 9b, 13, 14
reports,
a plausible mechanism of the reaction is
depicted in Scheme 5. Initially, in the presence of nBu NI and
4
TBHP, the propiophenone 1a is oxidized to form a radical
intermediate
A, which could react with the in situ-generated
iodine (I ) to give the key intermediate 2-iodo-phenylpropan-1-
2
one (
anion
B
C
). Then,
B undergoes nucleophilic attack by carbamate
generated in situ from CO and diethylamine to afford
2
the desired product 3aa (Path a). Alternatively, the reaction
might proceed through path b, in which 1a is oxidized to form
a cation intermediate D via radical A. Then the interaction of D
Scheme 3 Scope of amines. Reaction condition: 1a (1.0 mmol),
mmol), nBu NI (0.2 mmol), TBHP (6.0 mmol), DMF/DMSO (v:v = 2:1, 3
mL), CO (3 MPa), 90 C, 12 h. Isolated yields based on 1a
2 (7.0
4
o
2
.
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Scheme 5 A plausible mechanism of the transformation.
with the in situ generated carbamate anion
C could also
produce the final product 3aa
.
In summary, we have developed a nBu NI-catalyzed
8
9
1
(a) M. Aresta, A. Dibenedetto and A. Angelini, Chem. Rev.,
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2
014, 114, 1709; (b) Z.-Z. Yang, L.-N. He, J. Gao, A.-H. Liu and
oxidative cross-coupling of ketones, carbon dioxide and
amines using TBHP as the oxidant. This reaction represents the
first example of constructing organic carbamates via C-H bond
functionalization strategy, and thus has many merits, such as
the use of readily available substrates, high atom economy,
and metal-free catalysis. Further investigation on the reaction
mechanism and the application of this strategy to the
synthesis of other kinds of carbamates are currently ongoing in
our laboratory.
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Fundamental Research Funds for the Central Universities
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