Ruthenium catalyzes the synthesis of γ-butenolides fused with cyclohexanones

Article abstract of DOI:10.1039/c9cc00101h

Ruthenium(II)-catalyzed reactions of cyclic diazodicarbonyl compounds with β-ketoamides for chemo- and stereoselective construction of cyclohexanone-fused γ-butenolides are described. This study represents the first example of the addition of an enol substrate which is formed by the tautomerization of the β-ketoamides to the electrophilic carbene center for unusual cyclization through amide cleavage. The combined experimental and computational studies shed light on the mechanistic pathway favouring the unusual ring formation reaction instead of the involvement of the general carbonyl ylide intermediates for the product generation.

Full text of DOI:10.1039/c9cc00101h

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Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
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first methanofullerene derivatives of Sc
3
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DOI: 10.1039/C9CC00101H
Journal Name
COMMUNICATION
Ruthenium catalyzes the synthesis of γ-butenolides fused to
cyclohexanones
Received 00th January 20xx,
Accepted 00th January 20xx
Raju S. Thombal, Seoung-Tae Kim, Mu-Hyun Baik*c,b and Yong Rok Lee*a
a
b,c
DOI: 10.1039/x0xx00000x
www.rsc.org/
O
Ruthenium(II)-catalyzed reactions of cyclic diazodicarbonyl
compounds with β-ketoamides for chemo- and stereoselective
construction of cyclohexanone-fused γ-butenolides is described.
This study represents the first example for the addition of enol
substrate which is formed by the tautomerization of the β-
ketoamides to the electrophilic carbene center for the unusual
cyclization through amide cleavage. The combined experimental
and computational studies shed light on the mechanistic pathway
favouring the unusual ring formation reaction instead of the
involvement of the general carbonyl ylide intermediates for the
product generation.
O
O
O
O
O
O
HO
O
HO
O
H
aquilegiolide
OH
dihydroaquilegiolide
peniculide D
H
O
O
O
O
O
toluccanolide A
isoasterolid A
7,8-epialantolactone
Fig. 1 Selected natural products of cyclohexane-fused γ-butenolides.
γ-Butenolide is an important structural motif widely found in Mukaiyama-Michael reaction of silyloxy furans to
1
10
natural products and synthetic materials. Compounds crotonaldehyde or p-quinone methides, reagent-controlled
containing this substructure have been shown to possess a tandem reactions of vinyl epoxides with trifluoromethyl
1
1
wide range of biological activities and some of them have been ketone or nitrogen nucleophiles, Lewis and Brønsted acid-
2
12
used in traditional medicines. They also serve as valuable and promoted annulation of ketoacids with tertiary alcohols,
versatile building blocks for the synthesis of complex materials phosphine-promoted tandem reaction of allylic carbonates
3
13
and pharmaceuticals. For example, cyclohexane ring-fused γ- and trifluoromethyl ketones, palladium-catalyzed oxidative
butenolides appear as the characteristic skeletal core of cyclization/dimerization of 2,3-allenoic acids with 1,2-allenyl
4
14
bioactive natural products (Figure 1).
ketones, and boron-catalyzed aldol reactions of pyruvic acid
Owing to their importance and usefulness, much effort has with benzaldehydes.15
been devoted to construct these heterocyclic frameworks
Although a number of methodologies have been reported
using intra- and intermolecular cyclization protocols. Typical for the synthesis of simple γ-butenolides, there has been
intramolecular approaches include gold-catalyzed cascade limited development towards the construction of fused γ-
5
cyclization/oxidative cleavage reaction of (Z)-enynols,
butenolides. In this respect, the development of a facile and
6
carboxylation of 2,3-allenols with carbon dioxide, diphenyl efficient method for cyclohexane ring-fused γ-butenolides is
diselenide-catalyzed cyclization of β,δ-butenoic acids, and highly desirable. Although Marquez et al. reported a route for
7
ruthenium-catalyzed ring-closing metathesis of methallyl the synthesis of cyclohexane-fused γ-butenolide starting from
8
16
acrylates. Effective intermolecular approaches have also been pyrrolidine enamine in four steps, a one-pot construction of
9
reported, which include an organo- or Lewis acid-catalyzed
cyclohexanone-fused γ-butenolides has not yet been achieved.
Recently, transition metal-catalyzed reactions of diazo
compounds with various substrates have emerged as a
powerful arsenal for the synthesis of natural and unnatural
compounds. The creation of carbon-carbon bonds via C(sp)–
H /C(sp )–H /C(sp )–H bond insertions with carbenes are
a. School of Chemical Engineering, Yeungnam University, Gyeongsan 712-749,
Republic of Korea.
Department of Chemistry, Korea Advanced Institute of Science and Technology
KAIST), Daejeon 34141, Republic of Korea.
Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science
IBS), Daejeon 34141, Republic of Korea.
17
b.
2
3
(
c.
18-20
fundamental to the art of organic synthesis.
is known that metal carbenes derived from diazo compounds
In particular, it
(
†
Electronic Supplementary Information (ESI) available: [Experimental procedures,
characterization data, Computational Detail and X-ray crystallographic structure react with 1,3-dicarbonyl species and generate diverse 2-
and data for 3c (CCDC 1851023)]. See DOI: 10.1039/x0xx00000x
alkylated 1,3-dicarbonyl products; gold- or scandium-catalyzed
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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COMMUNICATION
Journal Name
Reported works
Table 1 Optimization of reaction conditionsa
View Article Online
DOI: 10.1039/C9CC00101H
O
O
R1 R2
N2 R3
O
O
HO
O
[
Au] or [Sc]
[Ag]
O
O
R3
R4
R4
R4
R3
O
O
[M]
additives
N2
O
R2 R1
R1 R2
C-H insertion
C-C insertion
O
O
O
NHPh
solvent
This work
1a
R2
2a
3a
O
HO
R1
R3
O
co-catalyst (mol%)
additive (mol%)
temp time yield
( C) (h) (%)
Ru
R3
entry catalyst (mol%)
solvent
o
b
/
R2
R1
O
O
PhHN
O
1 RuCl3 (10)
2 Ru(PPh ) Cl (10)
[RhCp Cl2]2 (5)
4 [RuCl2(p-cymene)]2 (2.5)
-
-
-
c
DCE
DCE
DCE
DCE
DCE
DCE
7
12 nr
0
O
c
OH
3 3
2
70 12 nr
Observed
R1 R2
*
nrc
3
70 12
70 12 nr
70 12 nr
O
C-C bond intermediate
c
-
N2
O
c
R2
5
-
AgSbF6 (10)
AgSbF6 (10)
R2
R1
*
R1
O
6 [RhCp Cl2]2 (5)
[RuCl (p-cymene)] (2.5) AgSbF6 (10)
70 12 21
70 12 46
70 12 35
70 12 62
+
Ru
Ru
DCE
7
2
2
+
O
8 [RuCl (p-cymene)] (2.5) AgSbF6 (10)/NaOAc (100) DCE
9 [RuCl2(p-cymene)]2 (2.5) AgSbF6 (10)/AgOAc 100) DCE
[RuCl (p-cymene)] (2.5) AgSbF6 (10)/PivOH (100) DCE
O
2
2
O
O
R3
R3
O
O
O
R3
70
8
74
NHPh
PhHN
C-O bond intermediate
R2
R1
O
NHPh
10
2
2
O
1
1
1 [RuCl2(p-cymene)]2 (2.5) AgSbF6 (10)/AcOH (100) DCE
70
70
70
rt
6
5
5
83
94
61
18
Not Observed
R1 R2
2 [RuCl2(p-cymene)]2 (2.5) AgSbF6 (10)/AcOH (200) DCE
13 [RuCl2(p-cymene)]2 (1.0) AgSbF6 (10)/AcOH (200) DCE
O
Ru
14
[
[
RuCl2(p-cymene)]2 (2.5)
RuCl2(p-cymene)]2 (2.5)
AgSbF6 (10)/AcOH (200)
DCE
24
toluene 70 10 52
15
AgSbF6 (10)/AcOH (200)
iPr
+
O
O
NHPh
PhHN
oxonium ion intermediate
16
17
1
[RuCl (p-cymene)] (2.5) AgSbF6 (10)/AcOH (200) dioxane
2
2
70 12
RuCl2(p-cymene)]2 (2.5)
AgSbF6 (10)/AcOH (200) CH3CN 70
39
68
O
O
[
+
8
R3
O
O
Ru
=
8 [RuCl2(p-cymene)]2 (2.5)
AgSbF6 (10)/AcOH (200) DMF
RuII
70 12 31
R3
O
O
O
Not Observed
a
Reaction conditions: 1a (1.1 mmol) and 2a (1.0 mmol) in solvent (5.0 mL)
under N . Isolated yield. Recovery of starting material 2a.
2
b
c
Scheme 1 Development of insertion reactions of diazo compounds into 1,3-dicarbonyl
compounds.
reactions engaging [RhCp*Cl
]
2 2
(5 mol%) or [RuCl
2 2
(p-cymene)]
(
2.5 mol%) together with AgSbF
6
(10 mol%) as a co-catalyst
formal insertion reactions of diazo compounds into C–H bonds
of 1,3-dicarbonyl compounds and silver-catalyzed insertion
reactions of diazo compounds into C–C bonds are also known
provided 3a in yields of 21% and 46%, respectively (entries 6
and 7). These reactions were further improved by additives
such as AgOAc, PivOH, and AcOH except NaOAc (entries 8–11).
(
Scheme 1).21 However, despite the significant advances in this
An optimum yield (94%) was obtained with [RuCl
2
(p-cymene)]
2
chemistry, metal-catalyzed reactions of diazo compounds with
β-ketoamides for the construction of heterocycles have not
been explored and successfully demonstrated as of this writing.
Recently, ruthenium catalysts have tremendously
contributed to the development of novel and efficient catalytic
(2.5 mol%) and AgSbF (10 mol%) in the presence of AcOH (200
6
o
mol%) in DCE at 70 C for 5 h (entry 12). Decreasing the
loading of [RuCl (p-cymene)] to 1.0 mol% or the reaction
2
2
temperature to room temperature resulted in significantly
lower yield (entries 13 and 14). Reactions in other nonpolar or
polar solvents such as toluene, dioxane, acetonitrile, and DMF
also led to inferior results (entries 15–18). The C–H insertion
product J was not observed at all under the optimized reaction
conditions.
2
2
reactions in various media. We previously reported on the
transition metal-catalyzed and thermal reactions of diazo
compounds with various substrates for the construction of
heterocycles.23 As a result of our continued exploration in this
area, we describe herein a novel and selective ruthenium-
catalyzed reactions of cyclic diazodicarbonyls with β-
ketoamides. These reactions were found to be highly chemo-
and stereoselective to provide cyclohexanone-fused γ-
butenolides via addition of the substrate in its enol form.
Interestingly, we propose a precise mechanism supported by
the DFT-calculations for this novel reaction that does not
involve the traditional participation of a carbonyl ylide
intermediate.24
The structure of 3a was determined by analyzing its spectral
1
data. The H NMR spectrum of 3a showed a characteristic enol
proton at δ 13.31 ppm as a singlet, a methyl peak on the vinyl
moiety at δ 2.40 ppm as a singlet, and two equivalent methyl
1
3
peaks at δ 1.14 ppm as a singlet. The C NMR exhibited a
carbonyl carbon of enone moiety at δ 196.7 ppm and an ester
carbonyl carbon on the lactone nucleus at δ 175.7 ppm. The
structure was further confirmed by single crystal X-ray
diffraction analysis of the structurally related compound 3c.
Having obtained the optimized conditions, we next explored
the substrate scope using various cyclic diazodicarbonyls 1b–1i
with amide 2a (Table 2). The reaction of diazo compounds 1b
without bearing any substituents on the 5-position of the 2-
diazo-1,3-cyclohexanedione ring provided 3b in 92% yield.
Treatment of 1c and 1d bearing methyl or isopropyl groups at
Our exploration commenced with the optimization of
reaction
dimethylcyclohexane-1,3-dione
conditions
by
employing
(1a) and
2-diazo-5,5-
3-oxo-N-
phenylbutanamide (2a) with the variation of catalysts and
additives under nitrogen atmosphere, as enumerated in Table
1
. The initial attempt with 10 mol% RuCl
3
or Ru(PPh
3
)
3
Cl
2
in
o
DCE at 70 C for 12 h, failed to provide product 3a (entries 1
5
3
-position on the 1,3-cyclohexanedione ring provided products
c and 3d in 92 and 90% yield, respectively. Similarly, the
and 2). Reactions with other catalysts such as [RhCp*Cl
mol%), [RuCl (p-cymene)] (2.5 mol%), and AgSbF (10 mol%)
entries 3–5) also failed to provide product 3a. However, the
2 2
] (5
2
2
6
reactions of 1e–1i bearing phenyl, aryl, or heteroaromatic
(
2
| J. Name., 2012, 00, 1-3
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Table 2 Substrate scope of various diazo compounds 1b–1i with 2a for diverse 3b–3i
View ticle Online
Table 3 Substrate scope of diazo compounds with various -ketoamArides 2b–2j
for diverse 4a–4t
DOI: 10.1039/C9CC00101H
O
[
RuCl2(p-cymene)]2
HO
N2
O
O
O
O
AgSbF6
HO
[
RuCl2(p-cymene)]2
R3
O
+
O
N2
O
NHPh
O
O
AgSbF6
R1
AcOH
O
R2
DCE, 70 o
C
R1
+
1
b-1i
2a
O
R3
AcOH
DCE, 70 oC
1
NHPh
R2
R1
R
O
1
1
3b-3i
1a, 1c-1e,
1h-1i, 1g
2b-2j
1
1
1
1
b R = H
1f R = 3,4-dimethoxyphenyl
R = benzo[d] [1,3]dioxol-5-yl
O
4a-4t
1
1g
1
c R = Me
3
3
3
1
1
2b R = Et
2e R = t-Bu
2h R = Ph
d R = i-Pr 1h R = 4-chlorophenyl
3
3
3
1
1
2c R = Pr
2f R = n-pentyl
2i R = 4-OMePh
e R = Ph
1i R = furan-2-yl
3
3
3
2
d R = i-Pr
2g R = n-undecanyl 2j R = 4-NO Ph
HO
2
1
O
3b R = H (4 h, 92%)
c R = Me (3 h, 92%)
d R = i-Pr(4 h, 90%)
3e R = Ph (5 h, 78%)
1
HO
O
HO
3
O
1
2
1
4a R =R = Me (4 h, 91%
4b R1= 4-ClPh, R2= H (4 h, 87%)
3
O
1
R1
O
R2
R2
R1
O
O
1
2
4
c R = furan-2-yl, R = H (5 h, 83%)
O
O
HO
R1
O
1
2
4
d R =R = Me (4 h, 90%)
HO
O
4g R1=R2= Me (4 h, 89%)
h R = Me, R = H
1
2
4e R = Me, R = H
1
2
4
O
(
4 h, 92%)
R1
3
3
3
3
O
R2
(4 h, 90%)
1
2
X-Ray crystal
structure of 3c
O
4f R = furan-2-yl, R = H
1
1
2
f R = 3,4-dimethoxyphenyl (4 h, 74%)
4i R = furan-2-yl, R = H
1
R1
O
(5 h, 82%)
g R = benzo[d] [1,3]dioxol-5-yl (4 h, 83%)
(
4 h, 86%)
1
h R = 4-chlorophenyl (5 h, 77%)
HO
O
HO
O
1
i R = furan-2-yl (4 h, 81%)
1
2
4
4
j R =R = Me (6 h, 78%)
k R = Ph, R = H (6 h, 79%)
1
2
R2
R1
O
R2
O
1
O
groups also successfully provided products 3e–3i in 74–83%
yields.
To extend the scope of the reaction, we further
investigated the reactions by employing different β-
O
R
1
2
4
l R =R = Me (4 h, 94%)
1
2
4
m R = i-Pr, R = H (4 h, 92%)
4n R1= benzo[d] [1,3]dioxol-
1
2
HO
4o R =R = Me (4 h, 95%)
1 2
O
2
4
p R = Ph, R = H (4 h, 91%) 5-yl, R = H (4 h, 83%)
ketoamides carrying various substituents (Table 3).
combination of 1a, 1h, or 1i with 3-oxo-N-phenylpentanamide
A
R2
R1
O
O
O
R3
HO
4
q R =R = Me, R = H (4 h, 90%)
1
2
3
1
2
3
(
(
2b) provided the desired products 4a (91%), 4b (87%), and 4c
83%), respectively. Similarly, the reactions of 1a, 1c, and 1i
4r R = i-Pr, R = H, R = H (4 h, 92%)
1
2
3
R2
R1
O
4s R =R = Me, R = OMe (4 h, 93%)
1
2
3
4t R = i-Pr, R = H, R = NO (6 h, 72%)
2
O
with 3-oxo-N-phenylhexanamide (2c) provided the products
4
3
d–4f with yields ranging from 82–92%, and that of 4-methyl-
-oxo-N-phenylpentanamide (2d) provided products 4g–4i
(
Scheme 3). The reaction of 1l with 2a or 2f in dichloroethane
o
at 70 C for 6 h led to 5c and 5d with yields of 85 and 89%,
respectively.
with yields from 86–90%. Importantly, with 4,4-dimethyl-3-
oxo-N-phen-ylpentanamide (2e) bearing a sterically hindered
t-butyl group, the desired products 4j and 4k were obtained in
This new methodology can be carried out at large scale (for
details see the ESI, Scheme S1). We further studied the
comparative reactivities of various diazo compounds with 3-
oxo-N-phenylbutanamide (2a) under standard reaction
conditions (for details see the ESI, Scheme S2).
To gain further insight into the mechanism of this unusual
reaction, density functional theory (DFT) calculations were
performed. Substrates 1a, 2a, and the experimentally
optimized conditions are employed for the calculation. The
most probable catalytic cycle is summarized in Scheme 4 and
7
8 and 79% yield, respectively. In addition, the reactions of β-
ketoamides 2f and 2g with long aliphatic chains were also
successful. For example, treatment of 1a, 1d or 1g with 3-oxo-
N-phenyloctanamide (2f) provided the products 4l–4n with
yields of 83–94%, and the reaction of 1a or 1e with 3-oxo-N-
phenyltetradecanamide (2g) provided products 4o and 4p in
9
5 and 91% yield, respectively. With ketoamides 2g–2i bearing
phenyl and aryl groups, the desired products were successfully
isolated. The combination of 1a or 1d with 3-oxo-N,3-
diphenylpropanamide (2h) led to 4q (90%) and 4r (92%), and
that with 3-(4-methoxyphenyl)-3-oxo-N-phenylpropanamide
O
O
HO
HO
O
N2
N2
O
O
O
1
j
1k
O
(2i) and 3-(4-nitrophenyl)-3-oxo-N-phenylpropanamide (2j)
O
O
O
NHPh
standard
condition
standard
condition
O
O
a 0%
2a
provided the expected products 4s and 4t at yields of 93% and
5
5b 78%
7
2%, respectively.
To study the ring size effect of diazo compounds, additional
Scheme 2 Further reactions of 5- and 7-membered ring diazo compounds 1j and 1k.
reactions were carried out using 2-diazocyclopentane-1,3-
dione (1j) and 2-diazocycloheptane-1,3-dione (1k) under this
standard reaction conditions (Scheme 2). The reaction of 1j
with 2a under the standard conditions did not afford the
desired product 5a. However, the reaction of 1k with 2a
successfully produced 5b in 78% yield.
O
O
N
O
R1
O
O
N2
O
standard
condition
R1
OH
NHPh
N
O
1
2a R = Me
1l
1
1
5c R = Me, 85%
d R = n-pentyl, 89%
2f R = n-pentyl
1
5
To further demonstrate the versatility of this novel protocol,
we
examined
additional
reactions
with
another
Scheme 3 Further reactions of 3-diazochromane-2,4-dione (1l) with 2a or 2f for the
construction of quinolinone ring-fused γ-butenolides 5c and 5d.
diazodicarbonyl compound, 3-diazochromane-2,4-dione (1l),
for the synthesis of quinolinone ring-fused γ-butenolides
This journal is © The Royal Society of Chemistry 20xx
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Journal Name
O
2
3
V. E. Juan Hikawczuk, J. Roberto Saad, O. S. VGiewioArrdticalne oO,nliCne.
O
+
Garcıa, T. Martın, V. S. Martın, M. E. Sosa and C. E. Tonn, J.
Ru
O
DOI: 10.1039/C9CC00101H
3a
O
N2
O
Nat. Prod., 2008, 71, 190.
N2
O
(a) B. Mao, M. Fañ anas-Mastral and B. L. Feringa, Chem.
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L. van Duuren and C. Mercado, J. Chem. Soc. C., 1966, 2100;
H
+
A
Ru
O
1
a
O
O
2
AgCl
+
Ru
(
d) N. Takeuchi, T. Kasama, R. Ikeda, K. Shimizu and K.
O
O
G
1a, 2AgSbF6
Hatakeyama, Chem. Pharm. Bull., 1984, 32, 2249.
O
B
4
(a) A. B. Smith. III and R. E. Richmond, J. Am. Chem. Soc.,
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[
(p-cymene)RuCl2]2
2
a'
O
O
OH
O
NHPh
NHPh
2a
2a'
(1.48)
(0.00)
O
Ru
Ru
O
O
O
O
OH
O
5
6
Y. Liu, F. Song, S. Guo, J. Am. Chem. Soc., 2006, 128, 11332.
S. H. Li, B. K. Y. Miao, W. M. Yuan and S. Ma, Org. Lett., 2013,
PhHN
PhH2N
C
O
F
Ru
1
5, 977.
D. M. Browne, O. Niyomura and T. Wirth, Org. Lett., 2007, 9,
169.
O
O
7
8
O
3
HO
D
NHPh
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Lett., 2005, 7, 1805; (b) B. Mao, K. Geurts, M. Fañ anas-
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Scheme 4 Proposed mechanism of the reaction.
9
the reaction energy profile is shown in Scheme S3 (for details
see the ESI, Computational study section).
10 B. M. Sharma, D. R. Shinde, R. Jain, E. Begari, S. Satbhaiya, R.
In summary, a chemo- and stereoselective protocol for
constructing various γ-butenolides was developed employing a
ruthenium(II)-catalyst that can activate cyclic diazodicarbonyls
to couple with β-ketoamides. This cascade reaction allows a
rapid and convenient synthesis of diverse cyclohexanone-fused
G. Gonnade and P. Kumar, Org. Lett., 2018, 20, 2787.
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1
1
1
γ-butenolides for the first time, which can be widely used as 14 S. Ma and Z. Yu, Angew. Chem., Int. Ed., 2002, 41, 1775.
1
5 D. Lee, S. G. Newman and M. S. Taylor, Org. Lett., 2009, 11,
486.
building blocks and key intermediates in the synthesis of
natural products and pharmaceuticals. DFT-calculations reveal
that the mechanism likely involves a metal-assisted C–C
5
1
6 S. K. Bagal, R. M. Adlington, J. E. Baldwin and R. Marquez, J.
Org. Chem., 2004, 69, 9100.
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followed by cyclization driven by aniline extrusion. The
theoretically plausible condensation route could be eliminated
based on overwhelmingly high energies associated with the
transition states and intermediates encountered during such
pathway.
This work was supported by the National Research
Foundation of Korea (NRF) grant funded by the Korea
government (MSIT) (2018R1A2B2004432) and the Priority
Research Centers Program (2014R1A6A1031189). This
236; (b) N. S. Y. Loy, A. Singh, X. Xu and C.-M. Park, Angew.
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Lee, Adv. Synth. Catal., 2018, 360, 3185.
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1
2
0 K. Liao, T. C. Pickel, V. Boyarskikh, J. Bacsa, D. G. Musaev and
H. M. L. Davies, Nature, 2017, 551, 609.
research was supported by the Nano Material Technology 21 (a) Z. Liu, P. Sivaguru, G. Zanoni, E. A. Anderson and X. Bi,
Development Program of the Korean National Research
Foundation (NRF) funded by the Korean Ministry of Education,
Angew. Chem., Int. Ed., 2018, 57, 8927; (b) Y. Xi, Y. Su, Z. Yu,
B. Dong, E. J. McClain, Y. Lan and X. Shi, Angew. Chem., Int.
Ed., 2014, 53, 9817.
Science, and Technology (2012M3A7B4049675).
MHB
2
2 (a) P. B. Arockiam, C. Bruneau, P. H. Dixneuf, Chem. Rev.,
acknowledges the financial support from Institute for Basic
Science (IBS-R10-D1).
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012, 112, 5879; (b) L. Ackermann, Chem. Rev., 2011, 111,
1315.
2
2
3 (a) L. Xia and Y. R. Lee, Adv. Synth. Catal., 2013, 355, 2361;
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Conflicts of interest
“There are no conflicts to declare”.
(
c) A. Padwa, S. M. Lynch, J. M. Mejía-Oneto and H. Zhang, J.
Org. Chem., 2005, 70, 2206.
2
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4
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DOI: 10.1039/C9CC00101H
Journal Name
COMMUNICATION
O
HO
O
O
O
R1
O
iPr
+
N2
O
X
R1
NHPh
N2
X
+
Ru
R
=
+
R
RuII
O
Ru
O
O
-
X= CH2, NMe
Unusual C-H insertion
and amide cleavage
R1
Ru

O
O

DFT-mechanistic insight
32 examples, yield up to 95%
Scalable
OH
NHPh
X

R
O

The combined experimental and computational study for Ru(II)-catalyzed reactions of cyclic diazodicarbonyl compounds with β-
ketoamides for cyclohexanone-fused γ-butenolides is described.
This journal is © The Royal Society of Chemistry 20xx
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