Full text of DOI:10.1021/acs.orglett.8b02612

Letter
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Ag(I)-Catalyzed [3 + 2]-Annulation of Cyclopropenones and
Formamides via C−C Bond Cleavage
Jiang-Tao Ren, Jia-Xin Wang, Hu Tian, Jing-Lei Xu, Hong Hu, Muhammad Aslam, and Meng Sun*
Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, Department of Chemistry &
Materials Science, Northwest University, Xi’an 710127, P. R. China
*
S Supporting Information
ABSTRACT: An unprecedented Ag-catalyzed [3 + 2]-annulation of cyclopropenones and DMF via C−C bond cleavage is
disclosed. This protocol exhibited excellent chemo- and regio-selectivity, and tolerated various functional groups. More
importantly, DMF served as the CO bond in the cycloaddition reaction, providing an efficient way to construct γ-
aminobutenolides. In addition, transesterification reaction occurred when DMF was replaced by esters.
7
a
or the past few years, C−C bond activation has been a
dimerizing reaction, in which the radical anion was involved.
Representative examples include Pd-catalyzed ring-opening
1
F
rapidly growing area of chemical research, which can
7b
provide a unique opportunity to perform chemical trans-
formations that would otherwise be unfeasible. Strained
molecules (three- and four-membered rings) are one of the
ideal candidates for C−C bond cleavage because of the
alkynylation of cyclopropenones and Au-catalyzed ring-
7c
expanding spiroannulation of cyclopropenones with enynes.
Very recently, Li reported Rh-catalyzed C−H bond coupling
7f,g
7e
with cyclopropenones
followed by nucleophilic attack.
2
powerful driving forces generated from strain release process.
Therefore, it is highly desirable to develop new synthetic
options featuring metal-catalyzed β-carbon elimination, which
will provide new appealing chemistry for the synthesis of more
diverse structures.
DMF (N,N-Dimethylformamide) is much more than a
solvent, and it can be used in many reactions as a multipurpose
Among these strained molecules, cyclopropenones (the
smallest “Hu
attention since their first preparation by Breslow et al. and
̈
ckel-aromatic” compounds) have drawn much
3
,4
Volpin and co-workers in 1959.
Recently, [3+n]-cyclo-
additions of cyclopropenones by C−C single bond cleavage
proved their wide utility in constructing many important
8
reagent. Recently, transformations of DMF to various building
blocks proved their diversity, serving as reaction precursors,
5
−7
skeletons (Scheme 1).
Generally, there are three different
such as −CHO, −CONMe , −NMe , −CO, −Me, and so on.
2
2
Scheme 1. Metal- and Organo-Catalyzed [3+n]-
Cycloadditions of Cyclopropenones
Nevertheless, to the best of our knowledge, employing CO π
bond of DMF to perform cycloaddition reaction has rarely
9
been reported. Herein, we successfully realized the Ag(I)-
catalyzed [3 + 2]-annulation of cyclopropenones and DMF via
β-carbon elimination followed by intramolecular nucleophilic
attack, affording a simple and efficient way to construct γ-
aminobutenolides. Further studies implied that this protocol
can also be extended to esters, but it delivered an unexpected
ester exchange product.
We initiated our studies with the optimization of the
reaction conditions for annulation of cyclopropenone 1a with
DMF 2a, and the results are given in Table 1. When AgOAc
was applied as the catalyst in neat condition at 80 °C, the
desired product 3a was isolated in only 24% yield (Table 1,
ways in this field: (a) organo-catalytic C−C bond cleavage by
5
nucleophilic addition; (b) C−C bond oxidative addition of
6a−d
low valent metal complexes;
(c) metal-catalyzed ring-
7
b,c,e−g
opening process via β-carbon elimination.
However,
compared with the well-developed first two modes, application
of the last strategy to create new chemistry is still under-
developed. The pioneering work demonstrated a Cu-promoted
Received: August 14, 2018
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b02612
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a,b
Table 1. Optimization of the Annulation Reaction
Conditions
Scheme 2. Scope of the Annulation Reactions
a
b
entry
catalyst
yield (%)
1
2
3
4
5
6
7
AgOAc
AgSbF6
AgOTf
AgBF4
Cu(OTf)2
CuCl2
24
92
80
82
trace
63
n.r.
84
68
TfOH
c
8
AgSbF6
AgSbF6
AgSbF6
d
9
e
1
0
40
1
1
n.r.
a
All the reactions were carried out in the presence of 0.2 mmol of 1a
b
c
d
and 1.0 mL DMF at 80 °C under Ar. Isolated yields. 100 °C. 60
e
°C. Under air condition.
a
All the reactions were carried out in the presence of 0.2 mmol of 1
b
and 1.0 mL formamide 2 at 80 °C under Ar. Isolated yields.
entry 1). Further examination proved that AgSbF was the best
6
choice, while switching to other silver salts led to lower yields
Table 2. Optimization of the Transesterification Reaction
Conditions
(Table 1, entries 2−4). It should be also noted that some
a
copper catalysts can also furnish this transformation, although
the product yield was not satisfied (Table 1, entries 5−6).
Some Brønsted acids were also investigated in this reaction,
but no annulation product was observed (Table 1, entry 7).
Moreover, changing the reaction temperature or altering other
factors could not improve the yield (Table 1, entries 8−11).
Control experiments verified that the Lewis acid silver catalyst
is necessary for this chemistry. Thus, the optimized reaction
conditions for the [3 + 2]-annulation reaction were eventually
b
entry
catalyst
additive (0.5 equiv)
TfOH
yield (%)
1
2
3
AgSbF6
AgOTf
AgOTf
55
78
96
chosen: AgSbF (10 mol %), DMF (1 mL) at 80 °C under
6
a
All the reactions were carried out in the presence of 0.2 mmol of 1a
argon for 20 h.
b
and 1.0 mL of ethyl formate at 40 °C under Ar. Isolated yields.
With the optimized conditions in hand, the scope and
generality of the annulation reactions were next investigated
(
Scheme 2). Diphenylcyclopropenone bearing electron-donat-
adding TfOH led to the generation of the coupling ester with
excellent yield (see the Supporting Information for more
details), which indicated a very different pathway may be
ing and electron-withdrawing groups in the benzene ring
underwent smooth transformation, and the corresponding
products 3a−3e were isolated in good to excellent yields. We
were also pleased to find that nonsymmetrical cyclopropenone
can proceed well in this reaction, showing that the C(O)−
C(Ph) bond was preferentially cleaved (3f). Meanwhile, this
transformation can be extended to dialkyl- or heteroaromatic
substituted cyclopropenones (3g−3h), thus broadening the
application of the current methodology. Moreover, a series of
formamides with various substituent groups on the N atom
were compatible, providing the desired [3 + 2]-cycloaddition
products in satisfactory yields (3i, 3k−3l, and 3o). In contrast,
extension of the N-bulky groups resulted in poor yields (3j and
10,11
involved in this process.
Further extension showed that
introduction of more steric groups on the O-atom provided the
corresponding products in moderate to good yields (5a−5c,
Scheme 3). However, as expected, the phenyl formate could
not participate in this transesterification process. Moreover,
this reaction tolerated cyclopropenones functionalized with a
variety of phenyl rings and alkyl substituents, and all of the
corresponding products were isolated in good yields (5d−5j,
Scheme 3).
To account for the transformation, a plausible reaction
7
mechanism is proposed on the basis of the previous literatures
3
m), and no reaction proceeded using free formamide (3n). It
and our observations (Scheme 4). First, species I was produced
by the reaction of cyclopropenone with the Ag catalyst, which
commenced both path A and path B to give the separate
products. For path A, the 1,2-addition of carbonyl of DMF to
cyclopropenone followed by a ring-opening process generated
amphiphilic intermediate III, which subsequently underwent
intramolecular nucleophilic addition to release the [3 + 2]-
annulation product. For path B, the in situ generated methoxyl
should be noted that acetamide can be tolerated in this
transformation, forming a sterically congested carbon quater-
nary center, albeit in lower yields (3p).
Further exploration demonstrated that formic esters can also
take part in this reaction with the assistance of Ag-catalyst, but
generate acrylic esters instead of the expected annulation
products (Table 2). Indeed, changing AgSbF to AgOTf and
6
B
DOI: 10.1021/acs.orglett.8b02612
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 3. Scope of the Transesterification Reaction
Conditions
catalyst was needed for the [3 + 2]-annulation reaction, and a
slightly lower yield was achieved with 10 mmol of cyclo-
propenone. Derivatization of the [3 + 2]-annulation product
has been carried out to prove the synthetic usefulness of this
strategy. The γ-aminobutenolide 3a can be converted to lactam
a,b
6
3
under hydrazine hydrate conditions. Moreover, treatment of
a with Grignard reagent led to formation of more congested
five-membered lactone 7.
In summary, we have reported the first Ag-catalyzed [3 + 2]-
annulation of cyclopropenones and DMF via C−C bond
cleavage. This protocol provided an important and novel way
to construct γ-aminobutenolides using DMF as a readily
available CO bond. Moreover, esters can also react with
cyclopropenones with modified conditions, and the ester
exchange products were achieved though the similar ring-
opening process. Further studies on the transformations of
cyclopropenones and DMF participant cycloaddition reactions
are in progress.
ASSOCIATED CONTENT
Supporting Information
■
*
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b02612.
a
All the reactions were carried out in the presence of 0.2 mmol of 1
b
and 1.0 mL of formate at 40 °C under Ar. Isolated yields.
Experimental details and characterization data for all
new compounds (PDF)
Scheme 4. Proposed Mechanism
AUTHOR INFORMATION
Corresponding Author
■
*
E-mail: sunmeng@nwu.edu.cn
ORCID
Meng Sun: 0000-0003-0257-4174
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (21702160), the China Postdoctoral Science Founda-
tion (2016M590967), the Shaanxi Provincial Postdoctoral
Science Foundation (2016BSHEDZZ21), and the “Top-rated
Discipline” Construction Scheme of Shaanxi Higher Education
for financial support.
anion attacked the activated cyclopropenone I followed by
rearrangement, further protonation to afford the acrylic ester.
We also investigated the reaction scale of our established
method (Scheme 5). For example, only 1 mol % loading of
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■
Scheme 5. Scale-Up of the Reactions and Derivatization of
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10) When methyl acetate was exposed to this reaction conditions,
a was the only product with a slightly lower yield (87%)..
11) When MeOH was added to this reaction instead of DMF under
(
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yield (92%).
D
DOI: 10.1021/acs.orglett.8b02612
Org. Lett. XXXX, XXX, XXX−XXX