Ag2O-promoted ring-opening reactions of cyclopropenones with oximes

Article abstract of DOI:10.1039/d0ob00601g

Ag2O-promoted ring-opening reactions of cyclopropenones with oximes is disclosed in this work, providing a direct route to 1,3-oxazinones. This method highlights a new reactivity of cyclopropenones which undergo 1,4-addition with oximes followed by β-carbon elimination to in situ generate a α-carbonyl ketene intermediate. This journal is

Full text of DOI:10.1039/d0ob00601g

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O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
View Article Online
DOI: 10.1039/D0OB00601G
COMMUNICATION
Ag O-Promoted ring-opening reactions of cyclopropenones with
2
oximes
Received 00th January 20xx,
Accepted 00th January 20xx
Ye-Fei Yang, Xiao-Bo Huang, Wen-Xia Gao, Yun-Bing Zhou,* Miao-Chang Liu* and Hua-Yue Wu
DOI: 10.1039/x0xx00000x
Ag
oximes is disclosed in this work, providing a direct route to 1,3-
oxazinones. This method highlights new reactivity of
cyclopropenones which undergo 1,4-addition with oximes
followed by β-carbon elimination to in situ generate a α-carbonyl
ketene intermediate.
O-promoted ring-opening reactions of cyclopropenones with Table 1. Optimization of reaction conditions.a
2
a
O
Ph
O
O
OH
Ph
Ph
N
catalyst
N
Ph Solvent, 80 o
N2, time
C
Ph
Ph
O
Ph
Ph
1a
2a
3aa
CCDC: 1917041
The cleavage of C-C bonds through ring opening of small-ring
compounds driven by the release of ring strain received much
scientific and technological interest, allowing for various
chemical transformations. Cyclopropenones are known to be
a diverse class of fascinating three-membered ring compounds
with broad potential applications in fields ranging from
entry
Ag salt
AgOAc
AgOTf
solvent
time (h) Yield (%)b
1
2
3
4
5
6
7
8
9
cyclohexane
cyclohexane
cyclohexane
cyclohexane
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
22
18
18
18
0
1
2
AgNTf
Ag SO
2
0
2
4
0
3
4
polymer cross-linking agents, ligands,
biosynthetic
CF CO Ag cyclohexane
0
3
2
5
6
7
intermediates to therapeutic leads, dendrimers and devices.
In particular, transition-metal-catalyzed ring-opening of
cyclopropenones through C-C bond oxidative addition
provided a unique and versatile route to a range of useful
compounds such as cyclic diones, pyranopyrandiones,
cyclopentadienone.10 The second strategy for ring-opening of
AgSbF
Ag CO
AgNO
6
cyclohexane
cyclohexane
cyclohexane
cyclohexane
cyclohexane
toluene
0
2
3
10
38
63
47
62
0
3
8
9
Ag
Ag
Ag
Ag
Ag
2
O
2
O
2
O
2
O
2
O
0c
1
cyclopropenones relied on organo-catalytic C−C bond cleavage
1
1
2
3
1
1
by nucleophilic addition. Organocatalysts would undergo 1,4-
addition with cyclopropenones, generating ketenes as a key
intermediate. In addition, transition-metal-catalyzed β-carbon
elimination emerged as a powerful strategy to construct more
1
dioxane
1
CH
3
CN
0
14
Ag O
2
THF
0
1
2
diverse structures from cyclopropenones. This strategy
involved an alkenyl-metal intermediate through 1,2-addition of
cyclopropenones with nucleophilic reagents. Herein, we report
the Ag-promoted ring-opening of cyclopropenones with
oximes, providing an efficient access to 1,3-oxazinone
derivatives.13 Though the reaction proceeded via β-carbon
elimination, nucleophilic oximes would undergo 1,4-addition
with cyclopropenones to generate ketene intermediate, which
was different from previous transition-metal-catalyzed β-
carbon elimination strategy.
1
1
1
1
5
6
7
8
Ag
Ag
Ag
Ag
2
O
2
O
2
O
2
O
DMF
0
DMSO
0
cyclohexane
cyclohexane
cyclohexane
66
82
28
19d
2
Ag O
aReaction conditions: oxime 1a (0.45 mmol), cyclopropenone
2
8
2
a (0.15 mmol), Ag salt (0.15 mmol), solvent (3.0 mL), under N ,
o
b
c
d
2
0 C. Isolated yield. Ag O (0.1 mmol) was used. The
reaction was performed with equimolar amounts of 1a and 2a.
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou
Our initial efforts focused on the identification of optimal
reaction conditions for the reaction between commercially
available diphenylcyclopropenone 1a and acetophenone
3
25035, People’s Republic of China. E-mail: zyb@wzu.edu.cn; mcl@wzu.edu.cn
†Electronic Supplementary Information (ESI) available:
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O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Page 2 of 4
COMMUNICATION
Journal Name
oxime 2a (Table 1). Inspired by previous work on Ag-catalyzed cyclopropenone containing a heterocyclic ring or asymmetric
View Article Online
1
9
DOI: 10.1039/D0OB00601G
annulation of cyclopropenones, we conducted the reaction cyclopropenones, no formation of the desired products was
between diphenylcyclopropenone 1a and oxime 2a in the observed (3E-3G).
presence of Ag salts. To our delight, it was found that AgOAc
successfully enabled this transformation in cyclohexane for 24
h at 80 ℃ under N
aa, the structure of which was determined by X-ray
crystallography (entry 1). Systematical screening for silver salts
showed that the use of Ag O was the best choice and afforded
the desired product 3aa with 63% yield (entry 9). Anions of
silver salts showed a significant influence on the reaction
2
atmosphere, providing the desired product Table 2. Scope of substrates.a
3
O R3 R4
O
R1
R2
HO
Ag2O
N
N
O
cyclohexane, N2
2
R3 R4
R1
R2
R2
0 oC,18 h
O
8
R1
1
2
3
efficiency. An equivalent Ag
yield, as demonstrated by the fact that reducing the amount of
Ag O to 0.7 equivalent led to a sharp decrease in the yield
entry 10), most probably due to large consumption of Ag
arising from the formation of silver mirror observed during the
reaction process. The use of toluene as the solvent also gave
rise to 3aa in 62% yield (entry 11). In contrast, the reaction in
polar solvent systems failed to provide the desired product
2
O was essential for achieving high
R
R = H, 3aa, 84%, 76%b
R
R = m-F, 3ia, 36%
R = m-Cl, 3ja, 61%
R = m-Me, 3ka, 64%
R = m-OMe, 3la, 74%
R = o-F, 3ma, 63%
Ph
R = o-Cl, 3na, 54%
R = Me, 3ba, 74%
R = OMe, 3ca, 80%
R = F, 3da, 71%
R = Cl, 3ea, 76%
O
O
O
2
Ph
Ph
Ph
Ph
N
O
(
2
O
N
O
O
Ph R = Br, 3fa, 52%
R = CF3, 3ga, 70%
R = NO2, 3ha, 0%
Ph
Ph
OMe
X
3
aa (entries 12-16). Shortening reaction time appropriately
improved the yield of the desired product 3aa (entries 17 and
8). Furthermore, the reaction performed with equimolar
O
O
O
R
Et
N
Ph
Ph
Ph
N
O
Ph
Ph
N
O
O
1
O
Ph
Ph
O
Ph
O
Ph
Ph
amounts of cyclopropenone and oxime delivered only 28%
yield of 3aa, as well as a mixture of phenylacetone (35%), 2a
Ph
Ph
X = O, 3sa, 40%
X = S, 3ta, 84%
R = n-Pr, 3pa, 78%
R = Ph, 3qa, 51%
R = CF3, 3ra, 0%
R = H, 3ra', 0%
3oa, 83%
(30 %) and spirolactone 2a’ (25%) (entry 19).
2
The scope of the methodology for Ag O-catalyzed ring
opening of cyclopropenones was explored (Table 2). First,
various oximes were subjected to the optimal reaction
conditions. As for acetophenone oximes substrates, p-
substituted groups on the benzene ring including both
electron-donating groups (3ba and 3ca) and electron-
withdrawing groups (3da-3ga) were tolerated under the
standard reaction conditions and afforded the corresponding
products with moderate to good yields, except for the strong
electron-withdrawing group such as nitryl (3ha). The reaction
to generate 3aa could be conducted on a gram scale. In
addition, acetophenone oximes bearing either m-substituted
groups or o-substituted groups on the benzene ring reacted
smoothly with cyclopropenone 1a (3ia-3na). Replacement of
methyl group of acetophenone oximes with other substituents
such as ethyl, n-propyl and phenyl resulted in moderate to
R3 R4
R
R
O
O
O
O
O
n
Ph
Ph
Ph
Ph
N
O
N
O
N
O
O
Ph
Ph
R
Ph
Ph
R3 = R4 =Ph, 3ua, 81%
R3 = R4 = Me, 3va, 91%
R3 = cyclochexyl, R4 = H,
n = 1, 3ya, 47%
n = 2, 3za, 59%
n = 3, 3z'a, 43%
R
R = F, 3A, 51%
R = Cl, 3B,62%
R = Me, 3C, 26%
3
wa, 59%
R3 = n-Pr, R4 = H,
3xa, 56%
O
R
O
(R)Ph
(Ph)R
N
O
N
O
R
O
R
O
R(Ph)
Ph(R)
R
R = m-Cl-Ph, 3D, 84%
R = 2-Me-thienyl, 3E, 0%
R = CH , 3F, 0%
R = i-Pr, 3G, 0%
3
3
good yields (3oa-3qa). In contrast, either CF -substituented
aReaction conditions: oximes 1 (0.45 mmol), cyclopropenones
oximes or benzaldoxime proved to be an unsuitable substrate
in the transformation (3ra and 3ra’). The substrates bearing a
heterocyclic ring such as furan and thiophene were
accommodated by the optimal reaction conditions (3sa and
2
N
(0.15 mmol), Ag
2
O (0.15 mmol), cyclohexane (3.0 mL), under
o
b
2
, 80 C. The reaction was conducted on 3 mmol.
Further control experiments were carried out to gain a
better understanding of the mechanistic pathway for the
Ag O-promoted ring opening of cyclopropenones (Scheme 1).
3
ta). Likewise, the methodology was effective for alkyl ketone
oximes which gave the desired products in high yields (3ua-
xa). Remarkably, spiroheterocyclic compounds could be
2
3
The addition of radical scavenges such as BHT, 1,1-
diphenylethylene and TEMPO still gave moderate yield of the
desired product 3aa, indicating that the possibility of a radical
way was ruled out (eq 1). Meanwhile, 2a was solely subjected
to the standard conditions and afforded spironolactone
compound 2a’ (eq 2). No reaction between 1a with 2a’ was
observed, ruling out a spirolactone intermediate during the
accessed in 43%-59% yields staring from corresponding cyclic
ketone oximes (3ya-3z’b). On the other hand, the scope with
respect
to
cyclopropenones
was
investigated.
Cyclopropenones bearing halogens successfully underwent
ring-opening reaction and provided the desired 1,3-oxazinone
derivatives with moderate to good yields (3A-3C).
Unfortunately, low yield (3D) was observed using CH
3
-
1
8
reaction process (eq 3). No formation of O -labeled product
substituted 2d as a substrate. Even worse, in the case of
2
| J. Name., 2012, 00, 1-3
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O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Journal Name
COMMUNICATION
O18 was added to the IV-1 from alkyl-substituted cyclopropenone woViuewldArtibclee Onnlionet
2
3
aa was detected when 10 equiv of H
model reaction, implying that oxygen atom in the heterocyclic stable, because alkyl group is unabDleOI:t1o0.10s3ta9b/Dil0izOeB00it60b1Gy
ring should be derived from oxime 1a (eq 4). Furthermore, the conjugation like aryl group, thus accounting for why alkyl-
addition of D O led to D-labeled product (d -3aa) with 90% of substituted cyclopropenones did not react.
2 1
deuterium incorporation, suggesting that water served as the
hydrogen source (eq 5). The large substituent on the N atom of
HO
3
aa could be removed by the combination of LiOH with H
O
2 2
N
Ag
R3
R2
O
O
I
O
O
(eq 6).
R1
R2
R1
O
R4
N
R3
R4
R3
R4
R3
R4
[Ag]
II
III
O
O
Ph
O
O
OH
Ph
N
N
standard conditions
O
(
1)
Ph
Ph
Ph scavenger (3 equiv) Ph
Ph
O
O
O
R3
R4
Ag
R2
1a
2a
3aa Ph
R3
R4
N
R2
R1
R3
O
Ag
R1
with BHT: 48% yield
with 1,1-diphenylethylene: 54% yield
with TEMPO: 57% yield
N
IV-2
IV-1
R4
V
Ph
Ph
Ph
standard conditions
2
a
(2)
Ag
R3
O
O
O
O
O
O
O
O
R3
R3
O
Ph
R3
R3
2
a'
R3
H O
2
N
N
N
R2
R2
51% yield
R2 R4
R1
R4
R4
R4
1 Ag
R4
Ph
R4
O
R1
H
Ph
Ph
O
R
Ph
O
standard conditions
VI
VII
1a
no reaction
(3)
O
2
a'
Scheme 2. Possible reaction mechanism.
O
O
Ph
O18
Ph
Ph
N
standard conditions
H2O18 (10 equiv)
1a
2a
(4)
Ph
Ph
Conclusions
O18-labeled 3aa
not detected
In conclusion, we have developed a practical protocol for the Ag-
promoted ring-opening reactions of cyclopropenones with oximes,
affording a novel and efficient entry to 1,3-oxazinones. This method
features easy accessibility of substrates, high functional group
tolerance and simple reaction conditions, which will offer an
opportunity to find synthetic applications. Furthermore, the
rearranged ring-opening reactions of other small-ring compounds
with oximes were underway in our laboratory.
O
Ph
O
Ph
Ph
N
standard conditions
1
a
2a
(5)
D2O (10 equiv)
O
Ph
D(H)
Ph
d1-3aa, 78%
9
0% of D incorporation
Ph
O
O
Ph
O
Ph
Ph
LiOH (2 equiv)
H O (3 equiv)
HN
O
N
2
2
(6)
O
Ph
Ph
THF, air, rt, 2 h
Ph
aa'
Ph
aa
3
Conflicts of interest
3
The authors declare no competing financial interest.
Scheme 1. Control experiments and further transformation of
the product 3aa. Standard conditions: Ag
2
O (0.15 mmol),
ACKNOWLEDGMENT
We are grateful for financial support from the National Natural
o
2
cyclohexane (3.0 mL), under N , 80 C.
Science Foundation of China (21901187 and 21372177).
On the basis of these results and previous references,12, 14
a
possible mechanism for Ag-promoted ring-opening reactions
of cyclopropenones with oximes was described in Scheme 2.
According to reference 19c, cyclopropenone exists two
resonance structures I and II. At the beginning, resonance
structure II undergoes nucleophilic attack by oxime to produce
intermediate III which is then fragmented into intermediates
IV-1 and V-2. The [4+2] cycloaddition between IV-A and IV-B
generates intermediate V. Next, the intermediate V reacts
with another cyclopropenone to deliver intermediate VI which
undergoes rearrangement/protonation sequence to provide
the desired product. Moreover, in-situ generated intermediate
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| J. Name., 2012, 00, 1-3
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