Copper(i)-catalyzed radical decarboxylative imidation of carboxylic acids with N-fluoroarylsulfonimides

Article abstract of DOI:10.1039/c6cc03227c

An efficient copper-catalyzed radical decarboxylative imidation reaction is presented. This strategy is carried out through the copper(i)-catalyzed decarboxylative C(sp³)-N and C(sp²)-N coupling of carboxylic acids with N-fluoroarylsulfonimides. The reaction shows good functional group tolerance and it provides a new approach for decarboxylative imidation. Preliminary mechanistic studies of this transformation suggest an involvement of N-centered radical species.

Full text of DOI:10.1039/c6cc03227c

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Copper(I)-catalyzed radical decarboxylative
imidation of carboxylic acids with
Cite this:DOI: 10.1039/c6cc03227c
N-fluoroarylsulfonimides†
Zhongxue Fang,*ab Yu Feng,a Hai Dong,a Dashan Lia and Tiandi Tanga
Received 18th April 2016,
Accepted 16th August 2016
DOI: 10.1039/c6cc03227c
www.rsc.org/chemcomm
An efficient copper-catalyzed radical decarboxylative imidation reac-
tion is presented. This strategy is carried out through the copper(I)-
catalyzed decarboxylative C(sp3)–N and C(sp2)–N coupling of
carboxylic acids with N-fluoroarylsulfonimides. The reaction shows
good functional group tolerance and it provides a new approach
for decarboxylative imidation. Preliminary mechanistic studies of
this transformation suggest an involvement of N-centered radical
species.
Amines are featured prominently in active pharmaceutical
ingredients, fine chemicals, agrochemicals, polymers and plas-
ticizing agents. They can also serve as versatile building blocks
in organic synthesis.1 Consequently, the introduction of an
amino group into a target molecule, in particular C-amination,2
has attracted considerable attention. In particular, enormous
efforts have been devoted to Schmidt reactions of carboxylic
acids,3 which provide a convenient entry to C–N bond formation
through decarboxylative amination. Nevertheless, traditional
methods for the synthesis of amines via decarboxylative amina-
tion were rather limited in practical application due to the
utilization of explosive azides as nitrogen sources,4 strong
sulfonic acids5 and toxic reagents.6 Therefore, the development
Scheme 1 Transition-metal catalyzed decarboxylative amination of
carboxylic acid.
of efficient synthetic routes for the synthesis of amines is very C(sp2)–N coupling of a-keto acids with arylamines in a photoredox
highly desirable.
mediated system (Scheme 1a).8 The groups of Mainolfi9 and Jia10
In recent years, a rapidly growing number of catalytic coupling successfully developed the decarboxylative C(sp2)–N coupling of
reactions with carboxylic acids as substrates have been reported.7 aryl carboxylic acids and N-nucleophiles, respectively (Scheme 1b).
Among these, transition-metal-catalyzed decarboxylative reactions The groups of Jiao11 and Bolm12 independently discovered oxida-
for C–N bond formation offer a new synthetic strategy for the tive decarboxylative C(sp)–N coupling of aryl propionic acids with
introduction of an amino group into a molecule. Recently, Lei and amines under copper catalysis (Scheme 1c). However, these
co-workers revealed the first example of radical decarboxylation methods often require carboxylic acids bearing a strong electron-
withdrawing group adjacent to the carboxyl group. Meanwhile,
transition-metal-catalyzed decarboxylative amidation with simulta-
a Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology,
School of Petrochemical Engineering, Changzhou University, Changzhou,
Jiangsu 213164, P. R. China
b Institute of Applied Chemistry and Environmental Engineering,
Yancheng Teachers University, Yancheng, Jiangsu 224002, P. R. China
† Electronic supplementary information (ESI) available: Experimental procedure
and spectra. See DOI: 10.1039/c6cc03227c
neous formation of C(sp3)–N and C(sp2)–N bonds has rarely been
investigated. Herein, we describe a novel route for in situ radical
decarboxylative C(sp3)–N and C(sp2)–N couplings of alkyl/vinyl-
substituted carboxylic acids with N-fluorobenzenesulfonimide
(NFSI) as the nitrogen source. The reaction exhibits high chemo-
and regioselectivity in forming various N-alkyl imide and N-vinyl
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imide products (Scheme 1d), which have shown great potential in NFSI under the optimized reaction conditions, and the results
medicinal chemistry and materials applications.13
are summarized in Scheme 2. First, phenylacetic acids with
In order to optimize the reaction conditions for this electron-donating substituents, such as methoxy and methyl
decarboxylative imidation, a model reaction of 2-naphthylacetic groups, were tolerated for this transformation, leading to the
acid (1q) and NFSI was carried out with various copper salts, target products 2a–2d in moderate to good yields. Meanwhile,
ligands and solvents (Table 1). Preliminary experimental results halo-substituted phenylacetic acid was tolerated in the amino-
showed that Cu salts, such as CuCl, CuCl2, CuI, and Cu(OAc)2, fluorination reaction, thus affording the corresponding products
were effective in the presence of 2,9-dimethyl-1,10-phenanthroline (2e–2l) in good yields. The electron-withdrawing 4-trifluoromethyl
L2 as a ligand and 1,2-dichloroethane (DCE) as solvent at 80 1C phenylacetic acid afforded 2m in 52% yield. Moreover, similar to
for 24 h under a nitrogen atmosphere (entries 1–4). Among the phenylacetic acids, acids with polycyclic and heterocyclic groups,
copper sources tested, CuI was the most effective catalyst, i.e. naphthalenes, benzofurans and thiophenes, were also compa-
affording the target decarboxylative coupling product 2q in tible, and provided the corresponding products 2n–2q in 53–85%
69% yield. After establishing CuI as the optimal catalyst, we isolated yields. Interestingly, the utilization of the 3-(4-methoxy-
focused on investigating other N-containing ligands (entries 5–8). phenyl)propionic acid 2r as the substrate was preferred for the
Gratifyingly, the N,N-dimethyl-1,2-ethanediamine L5 proved to be formation of the vinyl imide 4a in 77% yield (Scheme 3).
the most efficient and increased the yield of product 2q to 93%
Encouraged by these results of the decarboxylative C(sp3)–N
(entry 7). In contrast, solvents such as CH3CN, 1,2,3-trichloro- coupling reaction, we next extended the scope of the reaction
propane (TCP), 1,4-dioxane, toluene and ethanol showed inferior to cinnamic acids under the optimized reaction conditions
reactivity in this reaction and gave the corresponding product presented in Table S1 (ESI†). A range of cinnamic acids with
with yields ranging from 30% to 77% (entries 9–13). Polar solvents various substituents at the phenyl ring were tested, and led to
N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) the formation of products in 46% to 85% yields (Scheme 4).
resulted in only a trace amount of product 2q (entries 14 and 15).
The reaction did not occur without either CuI or the ligand
(entries 16 and 17). We therefore decided the utilization of CuI
(30 mol%) and L5 (30 mol%) in DCE at 80 1C under a nitrogen
atmosphere to be the optimized reaction conditions for this
protocol.
To examine the reaction scope of this decarboxylative imida-
tion reaction, various aliphatic carboxyl acids were reacted with
Table 1 Decarboxylative coupling of 2-naphthylacetic acid with NFSI
under different conditionsa
Entry
Catalyst
Ligand
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
CuCl
CuCl2
CuI
Cu(OAc)2
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
—
L2
L2
L2
L2
L1
L3
L5
L4
L5
L5
L5
L5
L5
L5
L5
—
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
CH3CN
TCP
1,4-Dioxane
Toluene
Ethanol
DMF
DMSO
DCE
DCE
58
48
69
46
87
80
93
80
54
77
52
30
Scheme 2 Reaction scope. Conditions: arylacetic acids (0.3 mmol), NFSI
(0.42 mmol), CuI (30 mol%), L5 (30 mol%) and DCE (2.0 mL); isolated yield.
9
10
11
12
13
14
15
16
17
62
Trace
Trace
None detected
None detected
L5
Scheme 3 Decarboxylative coupling with 3-(4-methoxyphenyl) propanoic
acid. The reaction was carried out under the optimal reaction conditions
reported above.
a
Reaction conditions: 2-naphthylacetic acid (0.3 mmol), NFSI (0.42 mmol),
catalyst (30 mol%), ligand (30 mol%) and solvent (2.0 mL). b Yield by LC.
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Scheme 5 Control experiments.
added instead of NFSI, the decarboxylative imidation product was
not observed [eqn (4)]. Therefore, the N-centered radical species
was plausibly generated via N–F bond cleavage of NFSI. The
parallel mechanistic experiments of cinnamic acids are shown in
Scheme S1 in the ESI,† which also probably proceeded via a free
radical process.14
In summary, we have developed a new facile copper-
catalyzed intermolecular decarboxylative imidation of carboxylic
acids by using commercially available NFSI as the nitrogen source,
which provides an efficient, direct and practical access to form
a new C(sp3)–N or C(sp2)–N bond. Meanwhile, studies on the
application of decarboxylative coupling reactions of carboxylic
acids to construct new C–C, C–heteroatom bonds are ongoing in
our laboratory.
Scheme 4 Reaction scope. Conditions: cinnamic acid (0.3 mmol), NFSI
(0.42 mmol), CuI (30 mol%), L4 (30 mol%) and CH3CN (2.0 mL); isolated
yield.
The authors wish to thank the National Natural Science
Foundation of China (21506017 and 21402014) and the Natural
Science Foundation of Jiangsu Province (BK20150258).
Cinnamic acid resulted in the desired vinyl imides 4a–4e in
67–85% yields, whereas cinnamic acid derivatives bearing halo-
substituents at the phenyl ring provided the vinyl imides 4g–4j
in 46–74% yields. The electron-withdrawing 4-trifluoromethyl
cinnamic acid afforded 2k in 69% yield. Even polysubstituted
cinnamic acids produced the target products 4m–4o in 47–81%
yields. Moreover, substrates bearing thiophene and naphthalene
moieties resulted in the corresponding decarboxylative products
4p and 4q in 57% and 67% yields, respectively.
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