A copper-catalyzed formal O-H insertion reaction of α-diazo-1,3- dicarbonyl compounds to carboxylic acids with the assistance of isocyanide

Article abstract of DOI:10.1039/c4cc00402g

A novel copper-catalyzed formal O-H insertion of α-diazo-1,3- dicarbonyl compounds to carboxylic acids has been developed, providing a straightforward synthetic method for α-acyloxy-1,3-dicarbonyl compounds, in which the activation of carboxylic acids by isocyanide plays a crucial role.

Full text of DOI:10.1039/c4cc00402g

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A copper-catalyzed formal O–H insertion
reaction of a-diazo-1,3-dicarbonyl compounds to
carboxylic acids with the assistance of isocyanide†
Zikun Wang,a Xihe Bi,b Yongjiu Liang,*a Peiqiu Liaob and Dewen Dong*a
Cite this: Chem. Commun., 2014,
50, 3976
Received 17th January 2014,
Accepted 24th February 2014
DOI: 10.1039/c4cc00402g
www.rsc.org/chemcomm
A novel copper-catalyzed formal O–H insertion of a-diazo-1,3-
dicarbonyl compounds to carboxylic acids has been developed,
providing a straightforward synthetic method for a-acyloxy-1,3-
dicarbonyl compounds, in which the activation of carboxylic acids
by isocyanide plays a crucial role.
a-Diazocarbonyl compounds have proved to be versatile precursors
of carbenes under thermolytic, photolytic, or transition metal-
promoted reaction conditions.1 Owing to their ease of preparation
and handling,2 a diverse range of a-diazocarbonyl compounds have
been employed in the cyclization,3 ylide transformation,4 the Wolff
rearrangement5 and X–H insertion (X = O, N, S, C or Si)6 reactions
for the synthesis of complex organic molecules.
Recently, Basso and co-workers developed a Passerini-like
3-component reaction of a carboxylic acid, an isocyanide and a
ketene or an a-diazocarbonyl compound to access stereodefined
captodative olefins, which was defined as K-3CR (Scheme 1).7 During
Scheme 1 The isocyanide-based 3-component reactions.
the course of our studies on the utilization of a-diazo-b-oxoamides in with acids mediated by hypervalent iodine reagents10 or toxic heavy
organic synthesis, we achieved the synthesis of 1,2,3-triazoles and metal oxidants,11 such as Pb(OAc)4,12 Tl(OAc)3,13 and Mn(OAc)3,14
pyrrol-3(2H)-ones in the presence of different catalysts.8 It is worth or the formal O–H insertion reactions of a-diazocarbonyl com-
noting that a-diazo-b-oxoamides could be transformed into ketene pounds to carboxylic acids.15 Among these methods, the latter has
intermediates catalyzed by copper(II). Inspired by this finding, displayed outstanding advantages with regard to fabricating the
we envisaged that captodative olefins might be synthesized from a-acyloxycarbonyl compounds including (1) mild reaction conditions;
a-diazo-b-oxoamides, isocyanides and carboxylic acids (Scheme 1). (2) high chemo-selectivity; (3) inexpensive and readily available
After a series of experiments, we found that a formal O–H insertion starting materials. However, it is a challenge to synthesize the closely
product of a-diazo-1,3-dicarbonyl compound to carboxylic acid related a-acyloxy-1,3-dicarbonyl scaffolds using this method due to
instead of captodative olefin was obtained (Scheme 1).
the relative instability of a-diazo-1,3-dicarbonyl compounds,1,16 and
a-Acyloxycarbonyl compounds as significant building blocks in expensive catalysts based on Pd or Rh are necessary to decompose
synthetic organic chemistry are traditionally prepared by the sub- the diazo group in most cases.15g,h In the present work, we wish
stitution reaction of a-halodicarbonyl compounds with alkaline to describe a straightforward procedure to access a-acyloxy-1,3-
carboxylates,9 the direct oxidative coupling of carbonyl compounds dicarbonyl compounds via a copper-catalyzed formal O–H inser-
tion reaction of a-diazo-1,3-dicarbonyl compounds to carboxylic
a Changchun Institute of Applied Chemistry, Chinese Academy of Sciences,
Changchun, 130022, China. E-mail: yjliang@ciac.ac.cn, dwdong@ciac.ac.cn
b Department of Chemistry, Northeast Normal University, Changchun, 130024,
China
acids with the assistance of isocyanide.
The reaction of a-diazo-b-oxoamide 1a, acetic acid 2a and
isocyanides was examined under different conditions (Table 1).
When 1a and CNCH2Ts (1.0 equiv.) were allowed to react with
acetic acid at 100 1C in the presence of Cu(AcO)2 (0.1 equiv.), the
reaction proceeded smoothly to furnish a product characterized as
† Electronic supplementary information (ESI) available: Experimental proce-
dures, analytical data, and copies of spectra of all compounds. See DOI:
10.1039/c4cc00402g
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Table 1 Screening of conditionsa
Entry
Cu
Isocyanide (equiv.)
Solvent
T (1C)
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
Cu(AcO)2
Cu(AcO)2
Cu(AcO)2
Cu(AcO)2
Cu(AcO)2
CuSO4
Cu(acac)2
CuBr2
CuI
CNCH2Ts (1.0)
none
None
None
None
None
None
None
None
None
None
None
DMF
Ethyl acetate
100
100
100
100
100
100
100
100
100
80
5
10
5
5
5
6
7
4
4
77
N.R.
84
83
71
46
43
CNCH2COOEt (1.0)
CNCH2COOEt (0.5)
CNCH2COOEt (0.3)
CNCH2COOEt (0.5)
CNCH2COOEt (0.5)
CNCH2COOEt (0.5)
CNCH2COOEt (0.5)
CNCH2COOEt (0.5)
CNCH2COOEt (0.5)
CNCH2COOEt (0.5)
Unidentifed mixture
Unidentifed mixture
Trace
N.R.
N.R.
9
10
11c
12c
Cu(AcO)2
Cu(AcO)2
Cu(AcO)2
10
10
10
100
Reflux
a
b
c
Reagents and conditions: 1a (1.0 mmol), 2a (4.0 mL), copper salts (0.1 mmol). Isolated yields. AcOH (5.0 mmol) was added.
Table 2 Synthesis of a-acyloxycarbonyl compounds 3 from a-diazo-1,3-
1,3-dioxo-1-(phenylamino) butan-2-yl acetate (77% yield) on the basis of
its analytical data (Table 1, entry 1). Obviously, CNCH2Ts did not act as
dicarbonyl compounds and acetic acida
a reactant in the reaction system. Thus, as a control experiment, the
same reaction excepting the inclusion of isocyanide exhibits no reaction
(entry 2). These results suggested that isocyanide played a key role in
the transformation process. It was found that the yield of 3a could
reach 84% when ethyl isocyanoacetate was employed (entry 3). The
Entry
1
R1
R2
3
Yieldb/%
decrease of isocyanide to 50 mol% had no significant effect on the
conversion (entry 4), while a further decrease of isocyanide would
reduce the yield of 3a (entry 5). In the presence of CuSO4 or Cu(acac)2,
the reaction of 1a and acetic acid could proceed, but the conversion was
very low (entries 6 and 7), whereas in the presence of CuBr2 or CuI, an
unidentified complex mixture was obtained (entries 8 and 9). It should
be noted that the reaction of 1a and acetic acid could almost not
proceed when conducted at 80 1C (entry 10). No reaction was observed
as indicated by TLC results when 1a, ethyl isocyanoacetate (0.5 equiv.),
acetic acid (5.0 equiv.) and Cu(AcO)2 (0.1 equiv.) were allowed to react in
DMF or ethyl acetate (entries 11 and 12).
With the optimized conditions in hand, a series of reactions of
a-diazo-b-oxoamides 1b–i bearing varied alkyl and aryl groups R1
and aryl amide groups R2 with acetic acid were carried out. As
shown in Table 2, all the reactions proceeded smoothly to afford
the corresponding a-acyloxy carbonyl compounds 3b–i in good to
high yields (entries 1–8). The synthetic efficiency was evaluated by
reacting a-diazo-b-dicarbonyls 1j, 1k and 1l with ketone and ester
groups (COR2) and acetic acid under the identical conditions
(entries 9–11). Next, we examined the reactions of miscellaneous
carboxylic acids with a-diazo-b-oxoamide 1a, and some of the
results are summarized in Scheme 2. The synthesis of the
a-acyloxy carbonyl compound was proved to be suitable for
the saturated and unsaturated carboxylic acids.
1
2
3
4
5
6
7
8
1b
1c
1d
1e
1f
1g
1h
1i
Me
Me
Me
Me
Me
Me
n-Pr
Ph
4-MeC6H4NH
2-MeC6H4NH
4-ClC6H4NH
2-ClC6H4NH
4-CF3C6H4NH
2,4-Me2C6H3NH
C6H5NH
C6H5NH
OEt
OEt
Me
3b
3c
3d
3e
3f
3g
3h
3i
82
77
81
79
75
73
86
78
83
69
74
9
10
11
1j
1k
1l
Me
Ph
Ph
3j
3k
3l
a
Reagents and conditions: 1 (1.0 mmol), 2a (4.0 mL), Cu(OAc)2
(0.1 mmol), ethyl isocyanoacetate (0.5 mmol), 100 1C, 4.0–5.0 h.
b
Isolated yields.
Scheme 2 The O–H insertion reactions of a-diazo-b-oxoamide 1a with
different carboxylic acids. Reagents and conditions: 1a (1.0 mmol), 2 (4.0 mL),
Cu(OAc)2 (0.1 mmol), ethyl isocyanoacetate (0.5 mmol), 100 1C, 4.0–5.0 h.
As previously mentioned, substrate 1a failed to react with acetic
acid in the absence of isocyanides, demonstrating that an isonitrilic
species is crucial for the success of the process. To further
investigate the effect of isocyanides, some experiments were con-
ducted. Firstly, 2-isocyanoacetate (0.5 mmol) and acetic acid The H1 NMR analysis of the resulting mixture indicated that ethyl
(4.0 mL) were mixed under stirring and kept at 100 1C for 1.0 h. isocyanoacetate was consumed, and an active intermediate A
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Notes and references
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Scheme 3 Probing the effect of isocyanide.
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Scheme 4 A plausible reaction mechanism.
seemed to be formed (Scheme 3). It is worth noting that 3a could be
obtained in 79% yield when 1a (1.0 equiv.) and Cu(OAc)2 (0.1 equiv.)
were added to the above mixture and stirred at 100 1C for 4.0 h. In
another experiment, after the solution of ethyl isocyanoacetate
(0.5 mmol) in acetic acid (4.0 mL) was run at 100 1C for 10 h,
formamide B was obtained in 82% yield. It is interesting to note that
no desired 3a was obtained when 1a (1.0 equiv.) and Cu(OAc)2
(0.1 equiv.) were added to the mixture or treated with B (0.5 equiv.)
in acetic acid at 100 1C. Actually, the reaction of isocyanides and
carboxylic acids was also reported via microwave irradiation or
thermolytic activation to produce formamides and anhydrides.17
On the basis of all the results obtained and the literature, a
plausible mechanism for the formal O–H insertion reaction of
a-diazo-1,3-dicarbonyl compounds to carboxylic acids is proposed.18
As shown in Scheme 4, the reaction of carboxylic acid and isocyanide
takes place to produce the intermediate A. In the presence of
Cu(AcO)2 at high temperature, a Cu-carbene C is generated from
a-diazo-1,3-dicarbonyl compound 1, which then reacts with A to give
an ylide intermediate D.19 Then, intermediate D takes a proton from
carboxylic acid 2 and undergoes a nucleophilic addition–elimination
reaction with the carboxylate to afford a-acyloxy-1,3-dicarbonyl com-
pound 3 along with the regeneration of A.
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In conclusion, a novel Cu(II)-catalyzed and isocyanide-assisted
formal O–H insertion reaction of a-diazocarbonyl compounds to
carboxylic acids has been developed, which provides a straightforward
synthetic access to a-acyloxycarbonyl compounds and describes an
unprecedented reaction pattern in the chemistry of O–H insertion.
19 For a recent review on copper–carbene, see: X. Zhao, Y. Zhang and
J. Wang, Chem. Commun., 2012, 48, 10162.
3978 | Chem. Commun., 2014, 50, 3976--3978
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