Silver-catalyzed ring-opening [3+2] annulation of cyclopropenones with amides

Article abstract of DOI:10.1039/c8nj04579h

A ring-opening [3+2] annulation reaction between cyclopropenones and amides was developed to produce 5-amino-2-furanones. Insertion of the carbonyl group of an amide to the C-C single bond of a cyclopropenone occurred efficiently in the presence of a catalytic amount of silver(i) triflate.

Full text of DOI:10.1039/c8nj04579h

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Silver-catalyzed ring-opening [3+2] annulation of
cyclopropenones with amides†
Cite this: New J. Chem., 2018,
42, 19178
Takanori Matsuda, * Yuki Tabata
and Hirotsugu Suzuki
A ring-opening [3+2] annulation reaction between cyclopropenones and amides was developed to
produce 5-amino-2-furanones. Insertion of the carbonyl group of an amide to the C–C single bond of a
cyclopropenone occurred efficiently in the presence of a catalytic amount of silver(I) triflate.
Received 9th September 2018,
Accepted 29th October 2018
DOI: 10.1039/c8nj04579h
rsc.li/njc
the latter of which has been employed as a solvent. It was later
found that copper(II), not rhodium(III), catalyzed the reaction,
Introduction
Cyclopropenones have fascinated organic chemists since the which produced a 5-(dimethylamino)-2-furanone through a ring-
first synthesis of diphenylcyclopropenone in 1959.1 Since then, opening [3+2] annulation. Herein, we report our study into the
a number of ring opening reactions of cyclopropenones have been catalytic ring-opening [3+2] annulation of cyclopropenones with
developed owing to their intrinsic strained three-membered ring amides for the synthesis of 5-amino-2-furanones. A range of
structure.2 Cyclopropenones undergo, upon treatment with an formamides, an acetamide, and a thioformamide were employed
appropriate promoter, various types of ring-opening annulation. for attempted coupling with disubstituted cyclopropenones in the
In particular, the ring-opening [3+2] annulation of cyclopropenones presence of a silver(I) triflate catalyst to afford five-membered
has been extensively studied, in which CQN, CQC, CQO, CQS, products.9
NQN, NQO, and CRC bonds couple with cyclopropenones to
form five-membered rings.3,4 Indeed, the insertion of a carbonyl
group into a cyclopropenone C–C bond is a straightforward method
Results and discussion
for synthesizing 2-furanones (butenolides),4 which are important
structural motifs found in various bioactive molecules.5 However, We began by exploring the reaction conditions required for the
only ring-opening [3+2] annulation reactions utilizing the carbonyl insertion of an amide carbonyl group into a cyclopropenone
groups of ketones and esters have been reported,4 with those based C–C single bond. Specifically, at 120 1C, diphenylcyclopropenone
on aldehydes and amides remaining unexplored. Moreover, the (1a) reacted with DMF (2a, 1a : 2a = 1 : 130) in the presence of
reported cyclopropenone–carbonyl coupling was conducted under 10 mol% Cu(OAc)2ÁH2O to yield 5-(dimethylamino)-3,4-diphenyl-
basic conditions using organic bases like DMAP and DBU as 2-furanone (3a) in 21% isolated yield after 4 h (Table 1, entry 1).
catalysts.4d,e A reaction employing a Lewis acidic metal has been Upon repeating the reaction in the presence of a gold(I) catalyst,
only limited to dimerization of cyclopropenones.4b,c
3a was afforded in 41% yield (entry 2), and a further significant
We recently reported K2CO3-catalyzed ring-opening [3+3]- increase in yield was observed when silver(I) salts were employed
type annulation of cyclopropenones with N-(pivaloyloxy)amides as catalysts. Among the various silver(I) salts examined, AgOTf
forming 1,3-oxazin-6-ones.6 In the course of our investigation into exhibited the highest activity (98% yield) toward the ring-
novel ring-opening annulation reactions of cyclopropenones6,7 in opening annulation (entry 3), followed by AgNTf2 (entry 4, 81%
the presence of catalytic amounts of rhodium(III) and copper(II) yield). Other acetate, nitrate, and tetrafluoroborate salts gave 3a
salts,8 we unexpectedly discovered a [3+2] coupling reaction in yields of 15–51% (entries 5–8), but no reaction was observed in
between a cyclopropenone and N,N-dimethylformamide (DMF), the presence of Ag2CO3 (entry 9). Upon lowering the reaction
temperature to 100 1C, 3a was obtained in 90% yield (entry 10),
and a considerable decrease in the yield was observed when the
reaction temperature was lowered further to 80 1C (entry 11, 48%
Department of Applied Chemistry, Tokyo University of Science, 1-3 Kagurazaka,
Shinjuku-ku, Tokyo 162-8601, Japan. E-mail: mtd@rs.tus.ac.jp
yield). In addition, no coupling reaction took place in the
absence of metal salts (entry 12), and no coupling was observed
† Electronic supplementary information (ESI) available: Experimental procedures
and characterisation data for new compounds. See DOI: 10.1039/c8nj04579h
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Table 1 Optimization of the reaction conditions
Table 2 Amide scope of the reaction under neat conditionsa
Yielda (%)
Entry
2
3b (% yield)
Entry
Catalyst (mol%)
Temp. (1C)
Time (h)
1
2
3
4
HCONMe2 (2a)
HCONEt2 (2b)
HCON(i-Pr)2 (2c)
HCONMePh (2d)
3a (95)
3b (98)
3c (88)
3d (68)
1
2
3
4
5
6
7
8
Cu(OAc)2ÁH2O (10)
(IPr)AuNTf2 (3)
AgOTf (10)
AgNTf2 (10)
AgOCOCF3 (10)
AgOAc (10)
AgNO3 (10)
AgBF4 (10)
Ag2CO3 (5)
AgOTf (10)
AgOTf (10)
None
120
120
120
100
100
100
100
100
100
100
80
4
3
2
2
2
5.5
2
2
1
21
41
98
81
51
29
28
15
NR
90
48
5
3e (67)
6c
3f (12)
9
10
11
12
2
3
4
7
HCONHMe (2g)
—
b
120
—
a
1a (0.100 mmol) was heated in 2 (0.50 mL) at 130 1C for 2 h in the
a
b
b
c
Isolated yield. Not detected.
presence of 10 mol% AgOTf. Isolated yield. 3 h.
at 130 1C in chlorobenzene in the presence of 20 mol% TfOH,
thereby indicating that the ring-opening annulation is catalyzed
by metal salts rather than by Brønsted acids.10
(2e) delivered 3d and 3e, respectively, in acceptable yields
(entries 4 and 5), while N-formylpyrrolidine (1f) gave a low yield
(entry 6), and the reaction with secondary formamide 2g was
unsuccessful (entry 7).
A possible mechanism for the ring-opening [3+2] annulation
of cyclopropenone 1a with amide 2a was tentatively proposed,
as illustrated in Scheme 1. As indicated, following the initial
coordination of the carbonyl oxygen atom of 1a to Ag+ to generate
A, the carbonyl oxygen atom of 2a then attacks the C1 atom of A to
form intermediate B.11 A final ring expansion step yields the
five-membered ring lactone 3a and concomitantly regenerates
Ag+. Analogous ring expansion step was proposed for other
ring-opening reactions of cyclopropenones.4b,c,12
We then examined the reaction of various formamides
(2a–g) with cyclopropenone 1a at 130 1C under neat conditions
where the amides themselves were present as solvents (Table 2).
Thus, the coupling of 1a with N,N-dimethyl-, N,N-diethyl-, and
N,N-diisopropylformamides (2a–c) proceeded efficiently to give
the corresponding 5-amino-2-furanones (3a–c) in excellent
yields (entries 1–3). In addition, the reactions of 1a with
N-methyl-N-phenylformamide (2d) and N-formylmorpholine
As the use of reactants as solvents is not ideal in terms of
purification and from an economical view point, we sought to
optimize the reaction conditions to incorporate a solvent
(Table 3). Thus, the reaction of 1a and 10 equiv. 2a at 120 1C
in chlorobenzene over 2 h was attempted, and an inseparable
mixture of the desired product 3a and the cyclopropenone
dimer, 1,2,6,7-tetraphenyl-4-oxaspiro[2.4]hepta-1,6-dien-5-one was
obtained, the latter of which was formed through a pathway
involving a radical anion of 1a (entry 1).4b,c However, the dropwise
addition of a chlorobenzene solution of 1a to a chlorobenzene
solution of 2a (10 equiv.) over 3 h followed by additional stirring for
1 h afforded 3a alone in 37% yield (entry 2). Following a thorough
Table 3 Optimization of the reaction conditions in the presence of a
solventa
Additional
Concentration
Entry of 1a in PhCl (M) (1C)
Temp. Dropping time reaction time Yieldb
of 1a (min)
(min)
(%)
c
1
2
3
4
5
—
0.5
0.25
0.25
0.25
120
120
120
120
130
0
180
80
40
80
120
60
40
80
40
—
37
74
55
97
a
A solution of 1a (0.100 mmol) in PhCl (0.20 or 0.40 mL) was added to a
b
c
solution of 2a (1.00 mmol) in PhCl (0.20 mL). Isolated yield. For-
mation of an inseparable mixture of 3a and 1,2,6,7-tetraphenyl-4-
oxaspiro[2.4]hepta-1,6-dien-5-one.
Scheme 1 Proposed mechanism.
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Table 4 Amide scope of reaction in the presence of a solventa
Table 5 Cyclopropenone scope for the reactiona
% yieldb in
% yieldb under the presence
neat conditions of solvent
3 (% yield with
Entry
2
10/20 equiv. of 2)b
Entry
1
3
1
2
3
4
HCONMe2 (2a)
HCONEt2 (2b)
HCON(i-Pr)2 (2c)
HCONMePh (2d)
3a (97/98)
3b (76/79)
3c (59/56)
3d (32/55)
1
2
3
4
5
1b (R1 = R2 = 4-MeC6H4)
3i 81
81
1c (R1 = R2 = 4-MeOC6H4) 3j 77
1d (R1 = R2 = 3-(O2N)C6H4) 3k 69
67c
d
—
1e (R1 = R2 = 2-thienyl)
1f (R1 = Me, R2 = Ph)
3l 87
3m 77
93
87e
5
3e (59/73)
a
Neat conditions: 1 (0.10 mmol) and 2a (0.50 mL); solvent-based
conditions: 1 (0.10 mmol) and 2a (20 equiv.) in PhCl, unless otherwise
b
c
noted. Isolated yield. A 1,1,2,2-tetrachloroethane solution of 1c was
added to a PhCl solution of 2a. Not examined due to the low solubility
of 1d in PhCl. 10 equiv. of 2a was used.
6
3f (92/96)
d
e
7
8
HCONHMe (2g)
HCONBn2 (2h)
3g (31/34)
3h (50/68)
a
To expand the scope of the silver(I)-catalyzed [3+2] annulation
of 1, various coupling partners bearing a carbonyl group were
screened. Specifically, N,N-dimethylacetamide (2i) was found to
be a viable but less reactive coupling partner, with the reaction
affording the desired annulation product 3n in yields of 33 and
30% (neat and solvent-based conditions, Scheme 2). All attempts
to improve the yield of 3n failed.
Other amides, including propanamide and 2-pyrrolidinone,
failed to couple with 1 under our conditions (Chart 1).
Moreover, as indicated, a 2-oxazolidone, a carbamoyl chloride,
a urea, a formate, and an aldehyde were all also unreactive in
the [3+2] annulation, thereby indicating that the present reac-
tion was only applicable to a narrow range of acyclic amides.
Continuing our investigation into possible coupling partners for
the annulation reaction revealed that N,N-dimethylthioformamide
(2j) reacts with 1a under similar conditions (Scheme 3).13 The
reaction of 1a with 2j at 130 1C in chlorobenzene in the presence
of a catalytic amount of AgOTf resulted in the formation of the
expected [3+2] annulation product 3o, accompanied by the same
A solution of 1a (0.100 mmol) in PhCl (0.40 mL) was added dropwise
to a solution of 2 (1.00 or 2.0 mmol) in PhCl (0.20 mL) over 80 min and
b
the mixture was stirred for 40 min at this same temperature. Isolated
yield.
optimization of the reaction conditions, 3a was obtained in 97%
yield by the dropwise addition of a 0.25 M chlorobenzene solution
of 1 to a chlorobenzene solution of 2a over 80 min at 130 1C
followed by stirring for 40 min at 130 1C (entry 5).
The amide scope of the reaction was then investigated, with
formamides 2a–h being subjected to the coupling reaction with
1a in the presence of chlorobenzene at 130 1C (Table 4). In
general, 10 equiv. of each formamide was sufficient to achieve
yields comparable to those obtained under neat conditions,
although reaction with 2d, 2e, and 2h, required the use of
20 equiv. of the corresponding formamides (entries 4, 5, and 8).
These solvent-based conditions were found to be more sensitive
to the bulkiness of the N-substituents of 2 compared to the
neat conditions (entries 1–3). While the reaction of 1a with
pyrrolidine 2f under neat conditions gave 3f in a poor yield of
12%, in the presence of chlorobenzene, 3f was obtained in
yields of 92 and 96% (10 and 20 equiv., entry 6). In addition, the
reaction using secondary amide 2g, which was unsuccessful
under neat conditions, afforded the desired product 3g in
yields of 31 and 34% (10 and 20 equiv., entry 7). We also found
that solid N,N-dibenzylformamide (2h) participated in the
coupling reaction (entry 8), but no such coupling was observed
with N,N-diphenylformamide.
Scheme 2 [3+2] Annulation of 1 with N,N-dimethylacetamide (2i).
The cyclopropenone scope for the ring-opening annulation
was also examined under both the neat and solvent-based
conditions (Table 5). As indicated, cyclopropenones 1b, 1c, and
1d bearing 4-methylphenyl, 4-methoxyphenyl, and 3-nitrophenyl
groups, respectively, provided the corresponding annulation pro-
ducts 3i–k (entries 1–3), and the use of di(2-thienyl)cyclopropenone
1e was also tolerated (entry 4). For the reaction of unsymmetrical
cyclopropenone 1f, a regioselective reaction took place to furnish a
single isomer 3m (entry 5).
Chart 1 Unsuccessful substrates.
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Scheme 3 [3+2] Annulation of 1 with N,N-dimethylthioformamide (2j).
heated for 40 min. After cooling to room temperature, the
reaction mixture was filtered through a plug of silica gel eluting
with hexane–AcOEt, and the filtrate was concentrated. The
residue was purified by preparative TLC or column chromato-
graphy on silica gel to afford furan-2(5H)-one 3.
Scheme 4 Reaction of 3a with HCl.
Conflicts of interest
amount of 4, which lacked the dimethylamino group.14 Details
regarding the observed reductive deamination remain unclear.
Finally, we demonstrated a derivatization of the [3+2] annulation
products. Upon heating 5-amino-2-furanone 3a at 100 1C in ethanol
in the presence of HCl, clean conversion to 5-ethoxy-2-furanone 5
was achieved in 81% isolated yield (Scheme 4).15
There are no conflicts to declare.
Acknowledgements
This work was supported by JSPS, Japan (Grant-in-Aid for
Scientific Research (C) No. 16K05783).
Conclusions
Notes and references
We successfully developed a silver(I)-catalyzed ring-opening
[3+2] annulation of cyclopropenones with amides to afford
5-amino-2-furanones. This reaction was based on insertion
of the carbonyl group of an amide into the C–C single bond
of a cyclopropenone. The present work adds to the synthetic
repertoire of 2-furanones as well as to the organic transformations
of N,N-dimethylformamide.16
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Experimental
General procedure for the silver(I)-catalyzed ring-opening
annulation of cyclopropenones 1 with amides 2: neat
conditions
A Schlenk tube was charged with AgOTf (0.010 mmol) and
cyclopropenone 1 (0.10 mmol), and the tube was evacuated and
backfilled with nitrogen. Amide 2 (0.50 mL) was added via a
syringe through the septum, and the mixture was heated at
130 1C for 2 h. After cooling to room temperature, the reaction
mixture was filtered through a plug of silica gel eluting with
hexane–AcOEt, and the filtrate was concentrated. The residue
was purified by preparative TLC or column chromatography on
silica gel to afford furan-2(5H)-one 3.
Dropwise addition
A Schlenk tube was charged with AgOTf (0.010 mmol), and
the tube was evacuated and backfilled with nitrogen. Amide 2
(1.00 or 2.00 mmol) and chlorobenzene (0.20 mL) were added
successively via a syringe through the septum, and the mixture
was heated at 130 1C. To the mixture was added dropwise a
solution of cyclopropenone 1 (0.10 mmol) in chlorobenzene
(0.40 mL) over 80 min, and the resulting solution was further
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