Redox-Neutral Annulation of Alkynylcyclopropanes with N-Aryloxyamides via Rhodium(III)-Catalyzed Sequential C-H/C-C Activation

Article abstract of DOI:10.1021/acs.joc.8b02661

Alkynylcyclopropanes have been used for the first time as coupling partners in transition-metal-catalyzed C-H functionalization. Specifically, a Cp?Rh^III-catalyzed regioselective annulation of alkynylcyclopropanes with N-aryloxyamides via redox

Full text of DOI:10.1021/acs.joc.8b02661

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Note
Redox-Neutral Annulation of Alkynylcyclopropanes with N-
aryloxyamides via Rhodium(III)-Catalyzed Sequential C-H/C-C Activation
Yang Li, Dandan Shi, Xin He, Yongzhuang Wang, Yuhai Tang, Junjie Zhang, and Silong Xu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02661 • Publication Date (Web): 31 Dec 2018
Downloaded from http://pubs.acs.org on December 31, 2018
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Redox-Neutral Annulation of Alkynylcyclopropanes with N-
aryloxyamides via Rhodium(III)-Catalyzed Sequential C−H/C−C
Activation
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Yang Li*, Dandan Shi, Xin He, Yongzhuang Wang, Yuhai Tang, Junjie Zhang, and Silong Xu*
Department of Chemistry, School of Science, and Xi'an Key Laboratory of Sustainable Energy Materials Chemistry, Xi’an
Jiaotong University, Xi’an, 710049, P. R. China.
Supporting Information Placeholder
EWG EWG
EWG
redox neutral
regioselective
E-selective





[Cp*RhCl2]2
(5 mol%)
1
EWG
3
+
O
R3
R2
Cu(OAc)2
(50 mol%)
MeOH, 60 °C
NHR1
R3
35-76% yields
24 examples
NHR1
2
R2
O
H
ABSTRACT: Alkynylcyclopropanes have been used for the first time as coupling partners in transition metal-catalyzed C−H
functionalization. Specifically, a Cp*RhIII-catalyzed regioselective annulation of alkynylcyclopropanes with N-aryloxyamides via redox-neutral
C−H/C−C activation has been developed, which affords highly functionalized 2,3-dihydrobenzofurans bearing an (E)-exocyclic carbon-carbon
double bond and a tetra-substituted carbon center in moderate to good yields with a broad substrate scope.
Transition metal-catalyzed C–H functionalization has been
established as a powerful and straightforward tool for the
construction of various molecular scaffolds.1 In particular, the
redox-neutral C–H functionalization by employing oxidizing
directing groups (DGs) represents a highly atom-economic
and eco-friendly protocol since it not only avoids the use of
stoichiometric amount of external oxidants but also increases
the synthetic diversity by engaging the DGs into bond
formations.2,3 To further enhance the versatility, recently a
strategy by merging C–H activation with C–C activation for
the generation of molecular complexity has attracted
considerable interests.4 In this regard, strained carbocycles of
three or four-membered rings have been thoroughly
investigated as coupling partners for the transition metal-
catalyzed C–H/C–C activation, allowing for the rapid
construction of complex molecular skeletons from a broader
scope of C–H bonds (Scheme 1, top).5, 6 In many of the cases,
the ease of scission of strained rings compensates the
relatively low reactivity of the C–H substrates.
C−H activation and cyclopropane chemistry,8 we report a
Cp*RhIII-catalyzed
regioselective annulation of
alkynylcyclopropanes 1 with N-aryloxyamides 2 via redox-
neutral C−H/C−C activation, which affords highly
functionalized 2,3-dihydrobenzofurans 3 bearing an (E)-
exocyclic carbon-carbon double bond and a tetra-substituted
carbon center9 in moderate to good yields with a broad
substrate scope (Scheme 1, bottom).
Scheme 1. Transition Metal-Catalyzed C−H/C−C
Activation of Arenes with Strained Carbocycles
To expand the scope of the C–H functionalization, we
conceived that the combination of the ring strain of
cyclopropanes7 and the reactivity of alkynes1 might bring up
some new reaction modes via sequential C−H/C−C activation.
It then occurs to us that alkynylcyclopropanes 1 might be a
valid coupling partner for transition metal-catalyzed C−H
functionalization (Scheme 1), which, to our knowledge,
remains to be unexplored. Herein, as part of our interest in
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Previous reported
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9
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
PhMe
CsOAc
15
11
38
54
57
59
46
63
DG
dioxane CsOAc
CH3CN CsOAc
MeOH CsOAc
MeOH CsOAc
MeOH KOAc
MeOH NaOAc
MeOH AgOAc
MeOH Cu(OAc)2 68
MeOH Cu(OAc)2 53
MeOH Cu(OAc)2 74
MeOH Cu(OAc)2 65
MeOH Cu(OAc)2 68
MeOH Cu(OAc)2 76
strained carbocycles
C-H & C-C activation
/annulation products
[TM]
10c [RhCp*Cl2]2
11d [RhCp*Cl2]2
H
R'
R
EWG
EWG
R
OH
R'
R
12
13
14
15
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
O
R'
16e [RhCp*Cl2]2
17f [RhCp*Cl2]2
18g [RhCp*Cl2]2
19h [RhCp*Cl2]2
20f,i [RhCp*Cl2]2
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R
R'
Ph
R
Ph
OH
R
R'
This work
O
NHR1
EWG
R2
2
EWG
EWG
EWG
a Unless specified, the reactions were carried out under N2 using
2.5 mol% catalyst, 50 mol% additive, 1.0 eq. of 2a (0.2 mmol)
and 1.2 eq. of 1a (0.24 mmol) in 2 mL solvent at rt for 16 h.
Isolated yields. 1.0 eq. CsOAc was used. 1.5 eq. of 1a was
adopted. e 50 mol% CsOAc was added. f The reaction was carried
out under 60 ºC. g The reaction was carried out under 70 ºC. h The
reaction was carried out under 50 ºC. i 5 mol% [RhCp*Cl2]2 was
used.
3
[Cp*RhCl2]2 (5 mol%)
NHR1
R3
Cu(OAc)2 (50 mol%)
b
R3
R2
1
MeOH, 60 C, 16 h
O
c
d
Initially,
the
reaction
of
dimethyl
2-
(phenylethynyl)cyclopropane-1,1-dicarboxylate (1a) with N-
phenoxyacetamide (2a) was performed in the presence of 2.5
mol% [Cp*RhCl2]2 and 50 mol% CsOAc in MeOH at room
temperature (Table 1, entry 1). To our delight, the reaction
afforded an annulative product dihydrobenzofuran 3a in 57%
yield with an (E)-exocyclic carbon-carbon double bond and a
tetra-substituted carbon center. The reaction conditions were
then optimized. It was found that other transition metal
catalysts such as iridium, ruthenium, and palladium were
ineffective for the annulation (entries 2 − 4). Screening of
solvents revealed that THF, DCE, PhMe, dioxane, and CH3CN
were all inferior, affording the product 3a in less than 38%
yields (entries 5−9). Increasing the amount of CsOAc or 1a
did not upgrade the yield of 3a (entries 10-11). We then turned
to the investigation of the additives. It was found that AgOAc
and Cu(OAc)2 delivered the product 3a in higher yields (63%
and 68%, respectively) compared to KOAc, NaOAc and
CsOAc (entries 12-15). If both CsOAc and Cu(OAc)2 were
added as the additives, product 3a was formed in only 53%
yield (entry 16). Finally, it was found that a temperature of 60
°C gave a higher yield of 74%, while the temperature of 50 °C
or 70 °C was both inferior offering lower yields (entries 17−
19). An increased catalyst loading of 5 mol% was beneficial,
which led to the formation of 3a in 76% yield (entry 20). Thus,
the optimized condition was established by performing the
reaction in MeOH in the presence of 50 mol% Cu(OAc)2 with
5 mol% [Cp*RhCl2]2 at 60 °C.
Table 2. Substrate Scopea
O
NHR1
EWG
R2
2
EWG
EWG
EWG
3
[Cp*RhCl2]2 (5 mol%)
NHR1
R3
Cu(OAc)2 (50 mol%)
1
R3
R2
MeOH, 60 C, 16 h
O
CO2Me
CO2Et
EtO2C
CO2Me
MeO2C
R2
MeO2C
NHR1
Ph
1 = Ac, 76% (75%)b
NHAc
NHAc
Ph
2 = Me, 57%
O
Ph
O
O
c
3a:
R
3c
, 66%
3d:
R
1 = Piv, 48%c
3b:
R
CO2Me
3e: R2 = tBu, 42%
CO2Me
MeO2C
3f:
R
2 = F, 52%
3g:
3h:
3i:
R
2 = Cl, 47%c
2 = Br, 48%
2 = CF3, 41%
MeO2C
R2
NHAc
Ph
R
O
NHAc
Ph
R
Me
c
3l:
36%
O
2 = Me, 75%c
3j:
CO2Me
R
CO2Me
2 = OMe, 58%c
MeO2C
F
3k:
R
MeO2C
CO2Me
NHAc
R3
3 = 4-MePh, 60%
NHAc
R3
Me
MeO2C
Table 1. Optimization of Reaction Conditionsa
O
O
3s:
3t:
R
3u:
3v:
R
3 = 4-MePh, 48%
3 = 4-OMePh, 56%
NHAc
R3
CO2Me
O
R
3 = 4-BrPh, 66%
R
O
NHAc
MeO2C CO2Me
MeO2C
3 = 4-MePh, 63%c
2a
3m:
R
CO2Me
CO2Me
3a
MeO2C
Me
MeO2C
Br
3 = 4-OMePh, 67%c
3 = 4-FPh, 59%c
3 = 4-ClPh, 55%c
3 = 4-BrPh, 69%c
3n:
3o:
3p:
3q:
3r:
R
R
R
R
conditions
NHAc
Ph
1a
Ph
O
NHAc
R3
NHAc
R3
entry catalyst
solvent additive
MeOH CsOAc
MeOH CsOAc
MeOH CsOAc
MeOH CsOAc
yieldb (%)
57
O
O
1
2
3
4
5
6
[RhCp*Cl2]2
3 = 3-MePh, 53%c
3 = 4-ClPh, 35%
3 = 4-BrPh, 40%
R
3w:
3x:
R
R
[IrCp*Cl2]2
trace
trace
trace
9
a Isolated yields are given; reaction conditions: under N2, 2 (0.2
mmol, 1.0 eq.), 1 (0.24 mmol, 1.2 eq.), [Cp*RhCl2]2 (5 mol%),
Cu(OAc)2 (0.1 mmol, 0.5 eq.) and MeOH (2 mL) were sealed in a
[RuCl2(p-cymene)]2
Pd(OAc)2
[RhCp*Cl2]2
[RhCp*Cl2]2
THF
DCE
CsOAc
CsOAc
25 mL Schlenk tube at 60 ºC for 16 h. b Yield of 2 mmol scale.
14
c
2
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CsOAc (0.1 mmol, 0.5 eq.) was used instead of Cu(OAc)2 (0.1
mmol, 0.5 eq.) and the reaction performed at rt.
1.05 (Scheme 2b). The result indicates that the C −H bond
cleavage might not be involved in the rate-limiting step.12
With the optimized conditions in hand,10 the substrate scope
of the Cp*RhIII-catalyzed annulation of alkynylcyclopropanes
with N-aryloxyamides was probed (Table 2). Compared to N-
phenoxyacetamide 2a, the bulky N-phenoxypivalamide 2a'
delivered the desired product 3b in a lowered yield (48%).
Alkynylcyclopropane 1a', bearing 1,1-diethyl esters, afforded
the product 3c in 66% yield. With alkynylcyclopropane 1a as
the partner, a series of para-substituted N-aryloxyamides with
either electron-donating or -withdrawing groups (R2)
participated well in the annulation, giving the corresponding
products 3d−i in 41−57% yields. Aryloxyacetamides with
meta-substituents afforded the corresponding products 3j and
3k as single regioisomers in 75% and 58% yields, respectively,
with the C−H activation taken place at less hindered positions.
However, ortho-methylphenoxyacetamide led to the formation
of product 3l in a lowered yield (36%), probably due to the
bulkiness hampering the reaction. Furthermore, a range of
alkynylcyclopropanes were investigated in the annulation with
N-phenoxyacetamide 2a. Alkynylcyclopropanes with various
aromatic substituents (R3) were feasible in the annulaiton,
producing the corresponding dihydrofurans 3m−r in moderate
to good yields. Substitution at both the N-aryloxyamides and
alkynylcyclopropanes was also applicable, as exemplified by
the formation of products 3s−x in moderate yields. Taken
together, the above Cp*RhIII-catalyzed annulation of N-
aryloxyacetamides with alkynylcyclopropanes offers a mild
redox-neutral synthesis of highly functionalized 2,3-
dihydrobenzofurans, a type of heterocycles enbedded in a
variety of natural products, bioactive compounds, and
pharmaceuticals.11 To demonstrate the practicality, a scale-up
reaction (2 mmol) of 1a and 2a was conducted which afforded
product 3a in 0.61 g, 75% yield (Table 2). The structure of the
Scheme 3. Proposed Mechanism
OH
NHAc
1/2 [Cp*RhCl2]2
O
SN2'
NHAc
3a
Cu(OAc)2
2a
Ph
V
Cp*Rh(OAc)2
CO2Me
CO2Me
2 AcOH
C-H activation
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protonolysis
*Cp
O
2 AcOH
O
NAc
RhIII
Ph
RhIII
N
I
Cp*
1a
O
Ph
migratory
insertion
CO2Me
CO2Me
CO2Me
CO2Me
O
O
N
oxidative
addition
IV
RhIIICp*
O
Ph
N
O
II
reductive
elimination
[RhICp*]
MeO2C
CO2Me
Ph
III
CO2Me
MeO2C
Based on the above results and literatures,3d, 5, 6 a plausible
mechanism for the redox-neutral Cp*RhIII-catalyzed
annulation of alkynylcyclopropanes with N-aryloxyacetamides
is proposed in Scheme 3. First, in the presence of Cu(OAc)2,
the active catalytic species Cp*Rh(OAc)2 is formed which
facilitates a facile ortho-C −H activation of 2a to afford a 5-
membered rhodacycle intermediate I.
A regioselective
migratory insertion of I into the alkyne of 1a forms a 7-
membered rhodacycle II with the cyclopropane moiety away
from rhodium center, probably due to the avoidance of the
steric clash.13 Subsequent reductive elimination of II occurs to
give a RhI specie III, which undergoes oxidative addition to
the N−O bond to generate the RhIII species IV. Finally,
protonolysis for the demetalation of IV gives the phenol
precursor V, which converts into the final product 3a via an
intramolecular SN2' ring opening of the vinylcyclopropane.3d
However, another pathway featuring the conversion of the 7-
membered rhodacycle II into a RhV-intermediate which
undergoes reductive elimination to form the product 3a cannot
be ruled out.17
In conclusion, an efficient Cp*RhIII-catalyzed regioselective
annulation of alkynylcyclopropanes with N-aryloxyamides via
redox-neutral C−H/C−C activation has been demonstrated,
which generates a range of highly functionalized 2,3-
dihydrobenzofurans bearing an (E)-exocyclic carbon-carbon
double bond and a tetra-substituted carbon center in moderate
to good yields with a broad scope. The reaction constitutes the
first example by using alkynylcyclopropanes as coupling
partners in transition metal-catalyzed C−H functionalization.
Further studies to explore the synthetic applications of the
reaction and developing new transition metal-catalyzed C−H
functionalizations with alkynylcyclopropanes are undergoing
in our laboratory.
1
dihydrofurans 3 was well identified by H, 13C NMR, HRMS,
IR analysis. It is noteworthy that all the dihydrofurans were
obtained in exclusive E-selectivity of the exocyclic double
bond. The E-configuration has been confirmed by NOE
analysis (see Supporting Information).
Scheme 2. Mechanistic Studies
3n
60% yield,
[Cp*RhCl2]2 (5 mol%)
1c
+
2a
(a)
(b)
no deuterium
incorporation
Cu(OAc)2 (50 mol%)
CD3OD, 60 C, 1 h
CO2Me
1c
MeO2C
O
[Cp*RhCl2]2 (5 mol%)
NHAc
H5/D5
Cu(OAc)2 (50 mol%)
CD3OD, 60 °C, 1 h
kH/D = 1.05
NHAc
4-OMePh
H4/D4
O
2a/2a
-d5
3n/3n
-d4
To gain insight into the mechanism of the annulation, the
reaction of 1c and 2a was performed in CD3OD solvent for 1 h
under otherwise identical conditions (Scheme 2a). The product
3n was isolated in 60% yield with no deuterium incorporation
observed, suggesting that the C −H activation step might be
irreversible under the reaction conditions. In addition, by using
2a/2a-d5 as substrates for parallel reactions with the annulation
with 1c, the kinetic isotope effect (KIE) was determined to be
EXPERIMENTAL SECTION
General Methods. All reactions and manipulations
involving air-sensitive compounds were performed using
standard Schlenk techniques. Anhydrous THF and dioxane
3
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were distilled from sodium. Anhydrous CH2Cl2 were distilled
2.32 (s, 3H), 1.95 (dd, J = 7.2, 4.7 Hz, 1H), 1.68 (dd, J = 9.1,
4.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 169.2,
166.9, 138.5, 131.7, 129.2, 119.6, 84.5, 80.7, 53.0, 52.9, 36.4,
22.5, 21.5, 17.8 ppm; FTIR (neat):  2953, 2360, 1727, 1511,
1436, 1370, 1330, 1283, 1206, 1126, 995, 944, 897, 816, 745,
706, 534 cm-1; HRMS (ESI-TOF) m/z: [M+H]+Calcd for
C16H17O4 273.1121; Found 273.1124.
from CaH2 under an atmosphere of N2. Anhydrous MeOH was
1
distilled from magnesium under N2 atmosphere. H, 13C and
19F NMR spectra were recorded on a 400 MHz Bruker AV400
spectrometer. Chemical shifts (δ values) were reported in ppm
with internal TMS (1H NMR), CDCl3 (13C NMR), or external
CF3CO2H (19F NMR) references, respectively. HRMS (ESI)
were determined on WATERS I-Class VION IMS QTof. The
IR spectra were measured on a NICOLET iS10 spectrometer.
Column chromatography was performed on silica gel
(200−300 mesh) using a mixture of petroleum ether (60−90
ºC)/ethyl acetate as the eluent.
Dimethyl 2-((4-methoxyphenyl)ethynyl)cyclopropane-1,1-
1
10
11
12
13
14
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dicarboxylate, (1c). Colorless liquid, yield 700mg (81%); H
NMR (400 MHz, CDCl3) δ = 7.30-7.26 (m, 2H), 6.79 (d, J =
8.8 Hz, 2H), 3.79 (s, 3H), 3.78 (s, 1H), 3.76 (s, 3H), 2.66 (dd,
J = 9.1, 7.3 Hz, 1H), 1.94 (dd, J = 7.2, 4.6 Hz, 1H), 1.68 (dd, J
= 9.1, 4.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ =
169.2, 166.9, 159.6, 133.2, 114.7, 113.9, 83.7, 80.4, 55.3, 53.0,
52.9, 36.4, 22.5, 17.8 ppm; FTIR (neat):  2953, 2839, 2359,
1725, 1606, 1509, 1436, 1371, 1331, 1288, 1245, 1207, 1172,
1126, 1025, 831, 773, 744, 650, 538 cm-1; HRMS (ESI-TOF)
m/z: [M+K]+Calcd for C16H16KO5 327.0629; Found 327.0630.
General procedure for synthesis of substrates 1a−g and
1a'. alkynylcyclopropanes 1a−g and 1a' were synthesized as a
following procedure analogous to that reported by Chang14 and
Waser15. In an oven dried flask, to
a solution of
ethynylbenzenes (10 mmol, 1 eq.) in Et3N (5 mL) were added
CuI (0.5 mmol, 95.2 mg), Pd(PPh3)4 (0.3 mmol, 210 mg), and
vinyl bromide (15 mmol, 1 M, 15.0 ml) at 0 °C. After stirred
for 16 h at 25 °C, the mixture was allowed to cool to rt and
then filtered through a pad of Celite with Et2O (100 mL). The
ether solution was washed with water (3 × 100 mL), dried over
Na2SO4, concentrated in vacuo, and purified by column
chromatography (petroleum ether/ethyl acetate = 100/0 to 20/1)
to give the arylenyne products in almost quantitative yields.
The arylenyne and Rh2(OAc)4 (0.03 mmol, 13.3) was then
dissolved in CH2Cl2 (50 mL) under N2 and heated to reflux in
an oil bath, subsequently the 2-diazomalonate ester (3 mmol, 1
eq.) was gradually added for 1 h and stirred for additional 3 h.
The reaction mixture was then filtered and evaporated under
reduced pressure. The crude products were purified by column
chromatography (petroleum ether/ethyl acetate = 10/1 to 5/1)
to afford the alkynylcyclopropanes 1a−g and 1a'.
Dimethyl
2-((4-fluorophenyl)ethynyl)cyclopropane-1,1-
dicarboxylate, (1d). Colorless liquid, 580 mg (70%); 1H NMR
(400 MHz, CDCl3) δ = 7.33-7.29 (m, 2H), 6.97-6.93 (m, 2H),
3.78 (s, 3H), 3.75 (s, 3H), 2.64 (dd, J = 9.1, 7.3 Hz, 1H), 1.93
(dd, J = 7.2, 4.7 Hz, 1H), 1.67 (dd, J = 9.2, 4.7 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ = 169.0, 166.8, 162.4 (d,
J = 249.5 Hz), 133.6 (d, J = 8.4 Hz), 118.7 (d, J = 3.5 Hz),
115.5 (d, J = 22.1 Hz), 84.9 (d, J = 1.3 Hz), 79.4, 53.0 52.8,
53.0, 36.3, 22.3, 17.5 ppm; 19F NMR (376 MHz, CDCl3) δ = -
110.8 ppm; FTIR (neat):  2954, 1727, 1601, 1507, 1436,
1371, 1331, 1283, 1207, 1126, 995, 878, 836, 807, 774, 746,
705, 640, 534 cm-1; HRMS (ESI-TOF) m/z: [M+Na]+Calcd for
C15H13FNaO4 299.0690; Found 299.0694.
Dimethyl
2-((4-chlorophenyl)ethynyl)cyclopropane-1,1-
1
dicarboxylate, (1e). Colorless liquid, yield 657 mg (75%); H
NMR (400 MHz, CDCl3) δ = 7.28-7.23 (m, 4H), 3.79 (s, 3H),
3.77 (s, 3H), 2.66 (dd, J = 9.1, 7.3, 1H), 1.95 (dd, J = 7.2, 4.7,
1H), 1.69 (dd, J = 9.1, 4.7, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ = 169.0, 166.8, 134.3, 133.0, 128.7, 121.2, 86.4,
79.4, 53.1, 52.9, 36.4, 22.4, 17.5 ppm; FTIR (neat):  2953,
2359, 1727, 1511, 1436, 1370, 1330, 1283, 1206, 1126, 995,
944, 897, 816 ,773, 744, 705 cm-1; HRMS (ESI-TOF) m/z:
[M+H]+Calcd for C15H14ClO4 293.0575; Found: 293.0573.
Dimethyl 2-(phenylethynyl)cyclopropane-1,1-dicarboxylate,
1
(1a). Colorless liquid, yield 619 mg (80%); H NMR (400
MHz, CDCl3) δ = 7.36-7.34 (m, 2H), 7.29-7.27 (m, 3H), 3.80
(s, 3H), 3.77 (s, 3H), 2.67 (dd, J = 9.1, 7.3 Hz, 1H), 1.96 (dd, J
= 7.2, 4.7 Hz, 1H), 1.69 (dd, J = 9.1, 4.6 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3)δ = 168.9, 166.8, 131.6, 128.2, 127.4,
122.6, 85.2, 80.4, 52.9, 52.8, 36.3, 22.3, 17.5 ppm; FTIR
(neat):  2953, 1725, 1598, 1491, 1436, 1369, 1329, 1283,
1207, 1126, 993, 944, 896, 877, 755, 691, 537, 496 cm-1;
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C15H14NaO4
281.0784; Found 281.0785.
Dimethyl
2-((4-bromophenyl)ethynyl)cyclopropane-1,1-
1
dicarboxylate, (1f). Colorless liquid, yield 766mg (76%); H
NMR (400 MHz, CDCl3) δ = 7.42-7.39 (m, 2H), 7.22-7.19 (m,
2H), 3.79 (s, 3H), 3.77 (s, 3H), 2.66 (dd, J = 9.1, 7.3 Hz, 1H),
1.96 (dd, J = 7.2, 4.7 Hz, 1H), 1.70 (dd, J = 9.2, 4.7 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ = 169.0, 166.8, 133.2,
131.6, 122.6, 121.6, 86.6, 79.5, 53.1, 53.0, 36.4, 22.4, 17.6
ppm; FTIR (neat):  2952, 2359, 1725, 1507, 1436, 1369,
1330, 1282, 1206, 1126, 1069, 1009, 943, 897, 822, 774, 702,
521 cm-1; HRMS (ESI-TOF) m/z: [M+H]+Calcd for
C15H14BrO4 337.0070; Found 337.0065.
Diethyl 2-(phenylethynyl)cyclopropane-1,1-dicarboxylate,
1
(1a'). Colorless liquid, yield 700 mg (80%); H NMR (400
MHz, CDCl3) δ = 7.36-7.33 (m, 2H), 7.28-7.24 (m, 3H), 4.30-
4.16 (m, 4H), 2.67 (dd, J = 9.1, 7.2 Hz, 1H), 1.92 (dd, J = 7.1,
4.6 Hz, 1H), 1.66 (dd, J = 9.1, 4.6 Hz, 1H), 1.28 (dt, J = 7.1,
4.3 Hz, 6H); 13C{1H} NMR (101 MHz, CDCl3) δ = 168.8,
166.6, 131.8, 128.3, 128.2, 122.8, 85.6, 80.5, 62.1, 61.9, 36.6,
22.2, 17.4, 14.3, 14.2 ppm; IR (neat):  2982, 2233, 1756,
1598, 1491, 1392, 1371, 1317, 1279, 1174, 964, 915, 862, 758,
698 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C17H19O4
287.1278; Found 287.1279.
Dimethyl2-(m-tolylethynyl)cyclopropane-1,1-dicarboxylate,
1
(1g). Colorless liquid, yield 498 mg (61%); H NMR (400
MHz, CDCl3) δ = 7.17-7.15 (m, 3H), 7.10-7.08 (m, 1H), 3.80
(s, 3H), 3.76 (s, 3H), 2.67 (dd, J = 9.1, 7.3 Hz, 1H), 2.29 (s,
3H), 1.95 (dd, J = 7.2, 4.7 Hz, 1H), 1.68 (dd, J = 9.1, 4.6 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 169.2, 166.9,
Dimethyl 2-(p-tolylethynyl)cyclopropane-1,1-dicarboxylate,
1
(1b). Colorless liquid, yield 645 mg (79%); H NMR (400
MHz, CDCl3) δ = 7.24 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 7.9 Hz,
2H), 3.79 (s, 3H), 3.76 (s, 3H), 2.66 (dd, J = 8.9, 7.4 Hz, 1H),
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138.0, 132.3, 129.2, 128.9, 128.2, 122.5, 84.9, 80.7, 53.1, 53.0,
TOF) m/z: [M+H]+Calcd for C25H28NO6 438.1911; Found
438.1911.
36.4, 22.5, 21.2, 17.8 ppm; FTIR (neat):  2953, 2360, 1727,
1601, 1486, 1436, 1330, 1288, 1266, 1208, 1126, 998, 950,
879, 784, 744, 690, 506 cm-1; HRMS (ESI-TOF) m/z:
(M+H)+Calcd for C16H17O4 273.1121; Found 273.1119.
Dimethyl (E)-2-(2-(2-acetamido-5-methyl-2-phenylbenzo-
furan-3(2H)-ylidene)ethyl)malonate, (3d). White solid, yield
49 mg (57%); M.p. = 186-187 °C; 1H NMR (400 MHz,
DMSO-d6) δ = 8.87 (s, 1H), 7.39-7.29 (m, 6H), 7.08 (d, J =
8.2 Hz, 1H), 6.85 (d, J = 8.2 Hz, 1H), 5.46 (t, J = 7.3 Hz, 1H),
3.71 (t, J = 7.4 Hz, 1H), 3.60 (s, 3H), 3.51 (s, 3H), 2.99-2.79
(m, 2H), 2.28 (s, 3H), 1.88 (s, 3H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ = 169.3, 168.9, 168.8, 158.4, 141.5, 140.5, 130.6,
129.6, 128.3, 128.0, 124.9, 124.7, 123.8, 119.0, 109.2, 96.6,
52.4, 52.3, 50.3, 27.2, 23.3, 20.6 ppm; FTIR (neat):  3281,
2918, 2359, 1749, 1728, 1671, 1522, 1480, 1434, 1354, 1281,
1251, 1225, 1153, 1075, 976, 948, 870, 819, 748, 703, 660,
593, 592, 551, 511 cm-1; HRMS (ESI-TOF) m/z:
[M+Na]+Calcd for C24H25NNaO6 446.1574; Found 446.1566.
General procedure for synthesis of N-aryloxyamides
2a−j and 2a'. The N-aryloxyamides 2a−j and 2a' were
synthesized following a procedure reported by Kelly16 and
Lu3d. Compounds 2a−j and 2a' are known compounds and all
data were in agreement with those reported.3d, 8f
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General procedure for Synthesis of 3. A seal tube with a
stir bar was added [RhCp*Cl2]2 (0.01 mmol, 5.0 mol%),
alkynylcyclopropanes 1 (0.24 mmol, 1.2 eq.), aryloxyamides 2
(0.20 mmol, 1 eq.) and Cu(OAc)2 (0.10 mmol, 0.5 eq.). The
tube was purged three times by vacuum and N2, then the
solvent (2 mL, 0.1 M) was added. The mixture was heated to
60 ºC in an oil bath and stirred for 16 h, which was then
concentrated in vacuum. The residue was purified by silica gel
column chromatography (petroleum ether/ethyl acetate = 5/1
to 1/1) to give products 3.
Dimethyl
(E)-2-(2-(2-acetamido-5-(tert-butyl)-2-phenyl-
benzofuran-3(2H)-ylidene) ethyl) malonate, (3e). White solid,
1
yield 40 mg (42%); M.p. = 116-117 °C; H NMR (400 MHz,
DMSO-d6) δ = 8.89 (s, 1H), 7.61 (s, 1H), 7.40-7.30 (m, 6H),
6.85 (t, J = 8.5 Hz, 1H), 5.53 (t, J = 7.6 Hz, 1H), 3.67 (t, J =
7.4 Hz, 1H), 3.60 (s, 3H), 3.53 (s, 3H), 3.00-2.82 (m, 2H),
1.88 (s, 3H), 1.29 (s, 9H); 13C{1H} NMR (100 MHz, DMSO-
d6) δ = 169.4, 168.9, 168.8, 158.3, 143.2, 141.4, 140.9, 128.3,
128.0, 127.2, 124.9, 123.3, 120.8, 118.6, 109.0, 96.8, 52.4,
52.3, 50.2, 34.1, 31.4, 27.12, 23.3 ppm; FTIR (neat,cm-1): 
3279, 2956, 2362, 1734, 1679, 1515, 1438, 1437, 1240, 1154,
959, 822, 698, 672 cm-1; HRMS (ESI-TOF) m/z:
[M+NH4]+Calcd for C27H35N2O6 483.2490; Found 483.2491.
Dimethyl
(E)-2-(2-(2-acetamido-2-phenylbenzofuran-
3(2H)-ylidene)ethyl)malonate, (3a). White solid, yield 62 mg
1
(76%); M.p. = 183-184 °C; H NMR (400 MHz, DMSO-d6) δ
= 8.90 (s, 1H), 7.53 (d, J = 7.5 Hz, 1H), 7.40-7.25 (m, 6H),
6.97 (t, J = 7.5 Hz, 2H), 5.49 (t, J = 7.4 Hz, 1H), 3.71 (t, J =
7.5 Hz, 1H), 3.60 (s, 3H), 3.50 (s, 3H), 3.00-2.79 (m, 2H),
1.88 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ = 169.5,
169.0, 168.9, 160.3, 141.4, 140.3, 130.2, 128.4, 128.1, 124.9,
124.4, 123.8, 121.0, 119.4, 109.7, 96.6, 52.5, 52.3, 50.3, 27.2,
23.4 ppm; FTIR (neat):  3284, 3033, 2953, 1732, 1678, 1606,
1588, 1561, 1340, 1270, 1241, 1156, 1026, 959, 748 , 700,
600, 551, 492 cm-1; HRMS (ESI-TOF) m/z: [M+Na]+Calcd for
C23H23NNaO6 432.1418; Found 432.1417.
Dimethyl (E)-2-(2-(2-acetamido-5-fluoro-2-phenylbenzo-
furan-3(2H)-ylidene)ethyl) malonate, (3f). White solid, yield
45 mg (52%); M.p. = 162-163°C; 1H NMR (400 MHz,
DMSO-d6) δ = 8.96 (s, 1H), 7.41-7.33 (m, 6H), 7.11 (dt, J =
9.0, 2.5 Hz, 1H), 6.96 (dd, J = 8.8, 4.3 Hz, 1H), 5.57 (t, J = 7.5
Hz, 1H), 3.71 (t, J = 7.4 Hz, 1H), 3.60 (s, 3H), 3.51 (s, 3H),
2.97-2.78 (m, 2H), 1.88 (s, 3H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ = 169.5, 168.9, 168.8, 156.7 (d, J = 235.6 Hz),
156.4, 141.0, 139.8 (d, J = 2.7 Hz), 128.4, 128.2, 124.9, 124.7
(d, J = 9.4 Hz), 120.9, 116.3 (d, J = 24.4 Hz), 110.8 (d, J =
25.1 Hz), 110.1 (d, J = 8.7 Hz), 97.3, 52.4, 52.3, 50.1, 27.1,
23.3 ppm; 19F NMR (376 MHz, DMSO-d6) δ = -123.3 ppm;
FTIR (neat):  3245, 2953, 2359, 1750, 1738, 1670, 1540,
1437, 1369, 1330, 1269, 1224, 1194, 1151, 970, 853, 816, 725,
564 cm-1; HRMS (ESI-TOF) m/z: [M+Na]+Calcd for
C23H22FNNaO6 450.1323; Found 450.1321.
Dimethyl
(E)-2-(2-(2-phenyl-2-pivalamidobenzofuran-
3(2H)-ylidene)ethyl)malonate, (3b). White solid, yield 44 mg
1
(48%); M.p. = 101-103 °C; H NMR (400 MHz, DMSO-d6) δ
= 8.15 (s, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.38-7.25 (m, 6H),
6.99-6.95 (m, 2H), 5.49 (t, J = 7.4 Hz, 1H), 3.68 (t, J = 7.5 Hz,
1H), 3.60 (s, 3H), 3.53 (s, 3H), 2.89 (t, J = 7.4 Hz, 2H), 1.12 (s,
9H); 13C{1H} NMR (100 MHz, DMSO-d6) δ = 177.2, 168.9,
168.8, 160.4, 141.6, 140.7, 130.0, 128.3, 127.9, 124.7, 124.3,
123.9, 120.9, 118.6, 109.7, 96.7, 52.5, 52.3, 50.4, 38.6, 27.1,
26.8 ppm; FTIR (neat):  2955, 1732, 1694, 1590, 1489, 1462,
1436, 1265, 1244, 1159, 1026, 961, 862, 732, 700, 567, 486
cm-1; HRMS (ESI-TOF) m/z: [M+NH4]+Calcd for C26H33N2O6
469.2333; Found 469.2335.
Dimethyl (E)-2-(2-(2-acetamido-5-chloro-2-phenylbenzo-
furan-3(2H)-ylidene)ethyl) malonate, (3g). White solid, yield
42 mg (47%); M.p. = 190-191°C; 1H NMR (400 MHz,
DMSO-d6) δ = 9.01 (s, 1H), 7.53 (d, J = 2.1 Hz, 1H), 7.42-
7.30 (m, 6H), 6.98 (d, J = 8.6 Hz, 1H), 5.58 (t, J = 7.5 Hz, 1H),
3.73 (t, J = 7.3 Hz, 1H), 3.61 (s, 3H), 3.51 (s, 3H), 2.98-2.78
(m, 2H), 1.88 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ
= 169.5, 168.9, 168.8, 159.9, 140.8, 139.1, 129.6, 128.4, 128.3,
125.7, 124.9, 124.5, 123.7, 121.1, 111.0, 97.5, 52.4, 52.3, 50.1,
27.2, 23.3 ppm; FTIR (neat):  3278, 2916, 2848, 2360, 1756,
1671, 1522, 1447, 1250, 1224, 1084, 973, 947, 885, 823, 703,
656, 591, 504 cm-1; HRMS (ESI-TOF) m/z: [M+Na]+Calcd for
C23H22ClNNaO6 466.1028; Found 466.1025.
Diethyl (E)-2-(2-(2-acetamido-2-phenylbenzofuran-3(2H)-
ylidene)ethyl)malonate, (3c). White solid, yield 58 mg (66%);
M.p. = 106-107°C;1H NMR (400 MHz, DMSO-d6) δ = 8.91 (s,
1H), 7.55 (d, J = 7.4 Hz, 1H), 7.41-7.26 (m, 6H), 6.97 (t, J =
7.1 Hz, 2H), 5.52 (t, J = 7.0 Hz, 1H), 4.11-3.92 (m, 4H), 3.64
(t, J = 7.4 Hz, 1H), 3.01-2.80 (m, 2H), 1.89 (s, 3H), 1.13 (t, J =
7.1 Hz, 3H), 1.07 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (100
MHz, DMSO-d6) δ = 169.4, 168.4, 160.3, 141.3, 140.2, 130.1,
128.3, 128.0, 124.9, 124.4, 123.8, 120.9, 119.5, 109.7, 96.6,
61.1, 60.9, 50.6, 27.1, 23.3, 13.8, 13.7 ppm; FTIR (neat): 
3731, 2983, 2352, 1794, 1727, 1518, 1454, 1394, 1223, 1154,
1024, 969, 932, 748, 967, 748, 697, 592 cm-1; HRMS (ESI-
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Dimethyl (E)-2-(2-(2-acetamido-5-bromo-2-phenylbenzo-
31 mg (36%); M.p. = 205-206 °C; 1H NMR (400 MHz,
DMSO-d6) δ = 8.87 (s, 1H), 7.41-7.31 (m, 6H), 7.11 (d, J =
7.4 Hz, 1H), 6.87 (t, J = 7.5 Hz, 1H), 5.50 (t, J = 7.3 Hz, 1H),
3.70 (t, J = 7.4 Hz, 1H), 3.60 (s, 3H), 3.50 (s, 3H), 2.97-2.78
(m, 2H), 2.22 (s, 3H), 1.89 (s, 3H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ = 169.3, 168.92, 168.91, 158.6, 141.5, 140.8,
130.9, 128.3, 128.0, 124.8, 123.1, 121.8, 120.8, 119.0, 118.7,
96.3, 52.4, 52.3, 50.3, 27.1, 23.4, 14.9 ppm; FTIR (neat): 
3284, 2916, 2848, 2359, 1747, 1731, 1670, 1521, 1433, 1217,
1153, 1072, 974, 947, 854, 741, 701, 551 cm-1; HRMS (ESI-
TOF) m/z: [M+Na]+Calcd for C24H25NNaO6 446.1574; Found
446.1572.
furan-3(2H)-ylidene)ethyl) malonate, (3h). White solid, yield
47 mg (48%); M.p. = 182-183°C; 1H NMR (400 MHz,
DMSO-d6) δ = 9.02 (s, 1H), 7.66 (s, 1H), 7.44-7.34 (m, 6H),
6.94 (d, J = 8.6 Hz, 1H), 5.58 (t, J = 7.4 Hz, 1H), 3.74 (t, J =
7.3 Hz, 1H), 3.61 (s, 3H), 3.51 (s, 3H), 2.98-2.78 (m, 2H),
1.89 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ = 169.6,
168.9, 168.8, 159.4, 140.8, 138.9, 132.4, 128.4, 128.3, 126.5,
126.3, 124.9, 121.2, 112.1, 111.7, 97.4, 52.5, 52.3, 50.1, 27.2,
23.3 ppm; FTIR (neat):  3278, 2915, 2848, 1755, 1671, 1521,
1462, 1432, 1249, 1222, 1147, 1083, 1034, 971, 945, 821, 703,
611, 589, 503 cm-1; HRMS (ESI-TOF) m/z: [M+Na]+Calcd for
C23H22BrNNaO6 510.0523; Found 510.0526.
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Dimethyl
(E)-2-(2-(2-acetamido-2-(p-tolyl)benzofuran-
Dimethyl
(E)-2-(2-(2-acetamido-2-phenyl-5-(trifluoro-
3(2H)-ylidene)ethyl)malonate, (3m). White solid, yield 54 mg
1
methyl)benzofuran-3(2H)-ylidene)ethyl)malonate,(3i). White
(63%); M.p. = 186-187 °C; H NMR (400 MHz, DMSO-d6) δ
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solid, yield 40 mg (41%); M.p. = 161-162°C; H NMR (400
= 8.87 (s, 1H), 7.52 (d, J = 7.6 Hz, 1H), 7.28-7.24 (m, 3H),
7.16 (d, J = 8.2 Hz, 2H), 6.97-6.93 (m, 2H), 5.46 (t, J = 7.4 Hz,
1H), 3.71 (t, J = 7.5 Hz, 1H), 3.61 (s, 3H), 3.52 (s, 3H), 2.99-
2.80 (m, 2H), 2.27 (s, 3H), 1.88 (s, 3H); 13C{1H} NMR (100
MHz, DMSO-d6) δ = 169.3, 169.0, 168.9, 160.3, 140.3, 138.5,
137.4, 130.1, 128.8, 124.9, 124.3, 123.9, 120.9, 119.0, 109.7,
96.6, 52.4, 52.3, 50.3, 27.2, 23.3, 20.6 ppm; FTIR (neat): 
3280, 2951, 2359, 1744, 1735, 1588, 1525, 1463, 1434, 1373,
1346, 1282, 1232, 1155, 1074, 1017, 969, 941, 864, 827, 738,
689, cm-1; HRMS (ESI-TOF) m/z: [M+H]+Calcd for
C24H26NO6 424.1755; Found 424.1756.
MHz, DMSO-d6) δ = 9.13 (s, 1H), 7.81 (s, 1H), 7.65 (d, J =
8.5 Hz, 1H), 7.45-7.35 (m, 5H), 7.14 (d, J = 8.5 Hz, 1H), 5.68
(t, J = 7.6 Hz, 1H), 3.76 (t, J = 7.2 Hz, 1H), 3.61 (s, 3H), 3.51
(s, 3H), 3.03-2.84 (m, 2H), 1.90 (s, 3H) ppm; 13C{1H} NMR
(100 MHz, DMSO-d6) δ = 169.7, 168.9, 168.8, 162.6, 140.4,
138.4, 128.4, 127.5 (q, J = 3.6 Hz), 124.9, 124.8, 124.5 (q, J =
271.7 Hz), 121.8, 121.7, 121.4, 121.0 (q, J = 3.3 Hz), 110.1,
98.0, 52.4, 52.3, 50.0, 27.2, 23.2 ppm; 19F NMR (376 MHz,
DMSO-d6) δ = -59.6 ppm; FTIR (neat):  3281, 2954, 2917,
2849, 1731, 1674, 1614, 1517, 1490, 1334, 1319, 1259, 1226,
1151, 1109, 1080, 971, 891, 837, 754, 701, 590 cm-1; HRMS
(ESI-TOF) m/z: [M+H]+Calcd for C24H23F3NO6 478.1472;
Found 478.1471.
Dimethyl
(E)-2-(2-(2-acetamido-2-(4-methoxyphenyl)-
benzofuran-3(2H)-ylidene)ethyl)malonate, (3n). White solid,
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yield 59 mg (67%); M.p. = 150-151 °C; H NMR (400 MHz,
Dimethyl (E)-2-(2-(2-acetamido-6-methyl-2-phenylbenzo-
furan-3(2H)-ylidene)ethyl)malonate, (3j). White solid, yield
64 mg (75%); M.p. = 186-187 °C; 1H NMR (400 MHz,
DMSO-d6) δ = 8.88 (s, 1H), 7.41-7.28 (m, 6H), 6.79-6.78 (m,
2H), 5.42 (t, J = 7.4 Hz, 1H), 3.69 (t, J = 7.4 Hz, 1H), 3.70 (s,
3H), 3.59 (s, 3H), 3.49 (s, 3H), 2.97-2.77 (m, 2H), 2.31 (s, 3H),
1.88 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ = 169.4,
169.0, 168.9, 160.6, 141.5, 140.4, 140.3, 128.3, 128.0, 124.8,
124.0, 121.8, 121.1, 117.9, 110.2, 96.8, 52.4, 52.3, 50.3, 27.2,
23.3, 21.3 ppm; FTIR (neat):  3282, 2953, 2359, 1747, 1730,
1676, 1522, 1506, 1460, 1434, 1333, 1285, 1230, 1154, 1075,
1019, 975, 942, 844, 740, 690, 592, 546, 518 cm-1; HRMS
(ESI-TOF) m/z: [M+Na]+Calcd for C24H25NNaO6 446.1574;
Found 446.1574.
DMSO-d6) δ = 8.84 (s, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.32 (d,
J = 8.8 Hz, 2H), 7.25 (t, J = 7.7 Hz, 1H), 6.97-6.90 (m, 4H),
5.46 (t, J = 6.9 Hz, 1H), 3.73-3.70 (m, 4H,), 3.62 (s, 3H), 3.55
(s, 3H), 3.01-2.81 (m, 2H), 1.87 (s, 3H); 13C{1H} NMR (100
MHz, DMSO-d6) δ = 169.3, 168.98, 168.96, 160.2, 159.1,
140.3, 133.3, 130.0, 126.4, 124.3, 124.0, 120.8, 118.8, 113.6,
109.6, 96.6, 55.2, 52.5, 52.3, 50.3, 27.2, 23.3 ppm; FTIR
(neat):  3264, 2916, 2848, 2359743, 1670, 1508, 1461, 1438,
1369, 1269, 1243, 1226, 1175, 1032, 954, 922, 858, 751, 719,
599, 546, 496 cm-1; HRMS (ESI-TOF) m/z: [M+Na]+Calcd for
C24H25NNaO7 462.1523; Found 462.1527.
Dimethyl (E)-2-(2-(2-acetamido-2-(4-fluorophenyl)benzo-
furan-3(2H)-ylidene)ethyl)malonate, (3o). White solid, yield
51 mg (52%); M.p. = 186-187 °C; 1H NMR (400 MHz,
DMSO-d6) δ = 8.96 (s, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.41 (dd,
J = 8.8, 5.4 Hz, 2H), 7.28 (t, J = 7.6 Hz, 1H), 7.19 (t, J = 8.9
Hz, 2H), 6.98 (t, J = 7.8 Hz, 2H), 5.49 (t, J = 7.4 Hz, 1H), 3.72
(t, J = 7.5 Hz, 1H), 3.60 (s, 3H), 3.51 (s, 3H), 3.02-2.80 (m,
2H), 1.88 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ =
169.9, 169.4, 169.3, 162.3 (d, J = 244.0 Hz), 160.6, 140.7,
138.1 (d, J = 2.9 Hz), 130.6, 127.6 (d, J = 8.4 Hz), 124.9,
124.0, 121.5, 121.0, 115.5 (d, J = 21.6 Hz), 110.2, 96.6, 52.9,
52.7, 50.7, 27.6, 23.7 ppm; 19F NMR (376 MHz, DMSO-d6) δ
= -114.8 ppm; FTIR (neat):  3283, 2953, 2849, 1750, 1731,
1671, 1525, 1473, 1433, 1254, 1229, 1197, 1155, 979, 954,
860, 817, 743, 703, 659, 593, 556, 497 cm-1; HRMS (ESI-TOF)
m/z: [M+Na]+Calcd for C23H22FNNaO6 450.1323; Found
450.1322.
Dimethyl
(E)-2-(2-(2-acetamido-6-methoxy-2-phenyl-
benzofuran-3(2H)-ylidene)ethyl)malonate, (3k). White solid,
1
yield 51 mg (58%); M.p. = 146-147 °C; H NMR (400 MHz,
DMSO-d6) δ = 8.88 (s, 1H), 7.42-7.29 (m, 6H), 6.60 (d, J =
2.1 Hz, 1H), 6.55 (dd, J = 8.5, 2.2 Hz, 1H), 5.32 (t, J = 7.4 Hz,
1H), 3.77 (s, 3H), 3.66 (t, J =7.2 Hz, 1H), 3.59 (s, 3H), 3.50 (s,
3H), 2.94-2.76 (m, 2H), 1.89 (s, 3H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ = 169.3, 168.9, 168.8, 161.9, 161.5, 141.4, 140.1,
128.3, 127.9, 124.8, 116.4, 116.1, 107.5, 97.4, 95.5, 55.4, 52.4,
52.2, 50.3, 27.1, 23.3 ppm; FTIR (neat):  3246, 2916, 2848,
3259, 1715, 1737, 1498, 1446, 1429, 1279, 1200, 1148, 1020,
974, 957, 843, 823, 790, 701, 660, 528 cm-1; HRMS (ESI-TOF)
m/z: [M+K]+Calcd for C24H25KNO7 478.1263; Found
478.1262.
Dimethyl (E)-2-(2-(2-acetamido-7-methyl-2-phenylbenzo-
furan-3(2H)-ylidene)ethyl)malonate, (3l). White solid, yield
Dimethyl (E)-2-(2-(2-acetamido-2-(4-chlorophenyl)benzo-
furan-3(2H)-ylidene)ethyl)malonate, (3p). White solid, yield
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49 mg (55%); M.p. = 194-195 °C;1H NMR (400 MHz,
7.41 (d, J = 8.2 Hz, 1H), 7.29 (d, J = 8.6 Hz, 2H), 6.82-6.80
(m, 2H), 5.41 (t, J = 7.4 Hz, 1H), 3.67 (t, J = 7.5 Hz, 1H), 3.60
(s, 3H), 3.49 (s, 3H), 2.97-2.76 (m, 2H), 2.32 (s, 3H), 1.88 (s,
3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ = 169.4, 168.84,
168.82, 160.5, 141.0, 140.5, 140.2, 131.1, 127.0, 124.1, 122.0,
121.1, 120.6, 118.7, 110.3, 96.2, 52.4, 52.2, 50.2, 27.2, 23.3,
21.3 ppm; FTIR (neat):  3592, 2955, 2362, 1741, 1675, 1520,
1474, 1281, 1233, 1159, 1109, 1074, 955, 808, 770, 693, 598
DMSO-d6) δ = 8.94 (s, 1H), 7.55 (d, J = 7.7 Hz, 1H), 7.42 (d,
J = 8.7 Hz, 2H), 7.37 (d, J = 8.7 Hz, 2H), 7.29 (t, J = 7.6 Hz,
1H), 7.01-6.97 (m, 2H), 5.49 (t, J = 7.4 Hz, 1H), 3.70 (t, J =
7.5 Hz, 1H), 3.60 (s, 3H), 3.49 (s, 3H), 3.01-2.79 (m, 2H),
1.89 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ = 169.5,
168.9, 168.8, 160.2, 140.5, 140.2, 132.7, 130.3, 128.3, 126.7,
124.5, 123.4, 121.2, 120.1, 109.8, 96.0, 52.4, 52.3, 50.2, 27.2,
23.3 ppm; FTIR (neat):  3275, 2917, 3259, 1746, 1733, 1670,
1532, 1490, 1459, 1436, 1336, 1270, 1241, 1156, 1094, 1015,
836, 765, 750, 683, 548, 503, 461 cm-1; HRMS (ESI-TOF)
m/z: [M+Na]+Calcd for C23H22ClNNaO6 466.1028; Found
466.1029.
cm-1;
HRMS
(ESI-TOF)
m/z:
[M+K]+Calcd
for
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
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39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
C24H24BrKNO6 540.0419; Found 540.0414.
Dimethyl (E)-2-(2-(2-acetamido-5-fluoro-2-(p-tolyl)benzo-
furan-3(2H)-ylidene)ethyl)malonate, (3u). White solid, yield
43 mg (48%); M.p. = 213-214 °C; 1H NMR (400 MHz,
DMSO-d6) δ = 8.89 (s, 1H), 7.33 (dd, J = 9.0, 2.6 Hz, 1H),
7.28 (d, J = 8.2 Hz, 2H), 7.17 (d, J = 8.1 Hz, 2H), 7.10 (dt, J =
9.0, 2.6 Hz, 1H), 6.93 (dd, J = 8.7, 4.3 Hz, 1H), 5.53 (t, J = 7.5
Hz, 1H), 3.71 (t, J = 7.4 Hz, 1H), 3.61 (s, 3H), 3.53 (s, 3H),
2.97-2.78 (m, 2H), 2.28 (s, 3H), 1.87 (s, 3H); 13C{1H} NMR
(100 MHz, DMSO-d6) δ = 169.3, 168.9, 168.8, 156.7 (d, J =
234.7 Hz), 156.4, 139.8 (d, J = 3.0 Hz), 138.1, 137.5, 128.8,
124.9, 124.8 (d, J = 12.0 Hz), 120.6, 116.2 (d, J = 24.1 Hz),
110.7 (d, J = 25.0 Hz), 110.1 (d, J = 8.6 Hz), 97.4, 52.4, 52.2,
50.2, 27.0, 23.2, 20.5 ppm; 19F NMR (376 MHz, DMSO-d6) δ
= -123.4 ppm; FTIR (neat):  3394, 2955, 2850, 1918, 1793,
1674, 1520, 1473, 1436, 1281, 1233, 1198, 1159, 1016, 955,
919, 863, 693, 770, 729, 598, 552, 465 cm-1; HRMS (ESI-TOF)
m/z: [M+NH4]+Calcd for C24H28FN2O6 459.1926; Found
459.1926.
Dimethyl (E)-2-(2-(2-acetamido-2-(4-bromophenyl)benzo-
furan-3(2H)-ylidene)ethyl)malonate, (3q). White solid, yield
67 mg (69%); M.p. = 191-192 °C; 1H NMR (400 MHz,
DMSO-d6) δ = 8.94 (s, 1H), 7.56 (d, J = 8.5 Hz, 3H), 7.30 (t, J
= 8.3 Hz, 3H), 7.00-6.97 (m, 2H), 5.49 (t, J = 7.4 Hz, 1H),
3.70 (t, J = 7.5 Hz, 1H), 3.60 (s, 3H), 3.50 (s, 3H), 2.97-2.83
(m, 2H), 1.89 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ
= 169.5, 168.9, 168.8, 160.2, 140.9, 140.2, 131.2, 130.3, 127.0,
124.5, 123.3, 121.2, 120.1, 109.9, 96.1, 52.5, 52.3, 50.2, 27.2,
23.3 ppm; FTIR (neat):  3279, 2916, 2848, 1755, 1672, 1521,
1462, 1432, 1368, 1325, 1250, 1147, 1083, 971, 946, 871, 821,
780, 750, 703, 664, 590, 546, 590, 503 cm-1; HRMS (ESI-TOF)
m/z: [M+Na]+Calcd for C23H22BrNNaO6 510.0523; Found
510.0522.
Dimethyl
(E)-2-(2-(2-acetamido-2-(m-tolyl)benzofuran-
3(2H)-ylidene)ethyl)malonate, (3r). White solid, yield 45 mg
Dimethyl
(E)-2-(2-(2-acetamido-5-fluoro-2-(4-methoxy-
(3v).
1
(53%); M.p. = 187-188 °C; H NMR (400 MHz, DMSO-d6) δ
phenyl)benzofuran-3(2H)-ylidene)ethyl)malonate,
= 8.86 (s, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.28-7.12 (m, 5H),
6.96 (t, J = 8.3 Hz, 2H), 5.49 (t, J = 7.4 Hz, 1H), 3.72 (t, J =
7.5 Hz, 1H), 3.60 (s, 3H), 3.52 (s, 3H), 3.00-2.80 (m, 2H),
2.30 (s, 3H), 1.88 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-
d6) δ = 169.3, 168.91, 168.89, 160.3, 141.3, 140.2, 137.4,
130.0, 128.7, 128.2, 125.4, 124.3, 123.9, 122.0, 120.8, 119.1,
109.6, 96.6, 52.4, 52.2, 50.3, 27.2, 23.3, 21.1 ppm; FTIR
(neat):  3546, 2955, 2359, 1733, 1670, 1489, 1458, 1436,
1264, 1239, 1199, 1158, 967, 866, 789, 730, 701, 492 cm-1;
HRMS (ESI-TOF) m/z: [M+Na]+Calcd for C24H25NNaO6
446.1574; Found 446.1573.
White solid, yield 51 mg (56%); M.p. = 159-160 °C; 1H NMR
(400 MHz, DMSO-d6) δ = 8.89 (s, 1H), 7.36-7.32 (m, 3H),
7.09 (dt, J = 9.0, 2.5 Hz, 1H), 6.93-6.90 (m, 3H), 5.53 (t, J =
7.5 Hz, 1H), 3.76-3.72 (m, 4H), 3.62 (s, 3H), 3.55 (s, 3H),
3.00-2.80 (m, 2H), 1.87 (s, 3H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ = 169.3, 168.9, 168.8, 159.2, 156.7 (d, J = 235.2
Hz), 156.3, 139.8 (d, J = 2.6 Hz), 133.0, 126.4, 124.9 (d, J =
9.4 Hz), 120.4, 116.1 (d, J = 24.6 Hz), 113.6, 110.7 (d, J =
25.8 Hz), 110.1 (d, J = 8.5 Hz), 97.4, 55.2, 52.4, 52.3, 50.2,
27.1, 23.2 ppm; 19F NMR (376 MHz, DMSO-d6) δ = -123.2
ppm; FTIR (neat):  3281, 2956, 2362, 1740, 1673, 1514,
1471, 1438, 1369, 1246, 1197, 952, 914, 863, 834, 804, 773,
691, 631, 595 cm-1; HRMS (ESI-TOF) m/z: [M+H]+Calcd for
C24H25FNO7 458.1610; Found 458.1608.
Dimethyl (E)-2-(2-(2-acetamido-6-methyl-2-(p-tolyl)benzo-
furan-3(2H)-ylidene)ethyl)malonate, (3s). White solid, yield
53 mg (60%); M.p. = 167-168 °C; 1H NMR (400 MHz,
DMSO-d6) δ = 8.80 (s, 1H), 7.38 (d, J = 7.7 Hz, 1H), 7.25 (d,
J = 8.2 Hz, 2H), 7.15 (d, J = 8.1 Hz, 2H), 6.78-6.76 (m, 2H),
5.38 (t, J = 7.3 Hz, 1H), 3.67 (t, J = 7.5 Hz, 1H), 3.60 (s, 3H),
3.51 (s, 3H), 2.96-2.77 (m, 2H), 2.30 (s, 3H), 2.27 (s, 3H),
1.87 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ = 169.2,
168.9, 168.9, 160.6, 140.5, 140.2, 138.6, 137.3, 128.7, 124.8,
123.9, 121.6, 121.2, 117.6, 110.1, 96.8, 52.4, 52.2, 50.3, 27.2,
23.3, 21.3, 20.5 ppm; FTIR (neat):  3301, 2954, 2850, 1757,
1732, 1675, 1515, 1434, 1257, 1256, 1145, 1009, 954, 804,
758, 689, 566 cm-1; HRMS (ESI-TOF) m/z: (M+Na)+Calcd for
C25H27NNaO6 460.1731; Found 460.1731.
Dimethyl
(E)-2-(2-(2-acetamido-5-bromo-2-(4-chloro-
(3w).
phenyl)benzofuran-3(2H)-ylidene)ethyl)malonate,
White solid, yield 37 mg (35%); M.p. = 188-189 °C; 1H NMR
(400 MHz, DMSO-d6) δ = 9.02 (s, 1H), 7.66 (d, J = 1.9 Hz,
1H), 7.46-7.37 (m, 5H), 6.95 (t, J = 9.4 Hz, 1H), 5.57 (t, J =
7.5 Hz, 1H), 3.72 (t, J = 7.3 Hz, 1H), 3.61 (s, 3H), 3.51 (s, 3H),
2.98-2.77 (m, 2H), 1.88 (s, 3H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ = 169.6, 168.9, 168.8, 159.2, 139.9, 138.8, 133.0,
132.6, 128.4, 126.8, 126.6, 125.9, 121.9, 112.3, 111.8, 96.9,
52.4, 52.3, 50.1, 27.2, 23.2; FTIR (neat):  3283, 2954, 2358,
1783, 1642, 1589, 1438, 1259, 1214, 1096, 972, 953, 886, 817,
758, 673, 580, 489 cm-1; HRMS (ESI-TOF) m/z:
[M+H]+Calcd for C23H22BrClNO6 522.0314; Found 522.0310.
Dimethyl (E)-2-(2-(2-acetamido-2-(4-bromophenyl)-6-me-
thylbenzofuran-3(2H)-ylidene)ethyl)malonate, (3t). White
1
solid, yield 66 mg (66%); M.p. = 184-185 °C; H NMR (400
Dimethyl
(E)-2-(2-(2-acetamido-2-(4-bromophenyl)-5-
MHz, DMSO-d6) δ = 8.89 (s, 1H), 7.54 (d, J = 8.6 Hz, 2H),
methylbenzofuran-3(2H)-ylidene)ethyl)malonate, (3x). White
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(d) Hummel, J. R.; Boerth, J. A.; Ellman, J. A. Transition-Metal-
solid, yield 40 mg (40%); M.p. = 200-201 °C; H NMR (400
MHz, DMSO-d6) δ = 8.88 (s, 1H), 7.54 (d, J = 8.6 Hz, 2H),
7.34 (s, 1H), 7.28 (d, J = 8.6 Hz, 2H), 7.10 (d, J = 8.4 Hz, 1H),
6.87 (d, J = 8.2 Hz, 1H), 5.45 (t, J = 7.4 Hz, 1H), 3.69 (t, J =
7.4 Hz, 1H), 3.60 (s, 3H), 3.51 (s, 3H), 2.99-2.78 (m, 2H),
2.28 (s, 3H), 1.88 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-
d6) δ = 169.4, 168.87, 168.86, 158.3, 141.1, 140.4, 131.2,
130.8, 129.9, 127.0, 124.6, 123.3, 121.1, 119.8, 109.4, 96.1
52.4, 52.2, 50.2, 27.2, 23.3, 20.6; FTIR (neat):  3275, 2922,
2353, 1740, 1668, 1519, 1480, 1435, 1336, 1227, 1156, 1072,
975, 814, 684, 590 cm-1; HRMS (ESI-TOF) m/z:
[M+Na]+Calcd for C24H24BrNNaO6 524.0679; Found
524.0683.
Catalyzed C–H Bond Addition to Carbonyls, Imines, and Related
Polarized π Bonds. Chem. Rev. 2017, 117, 9163−9227. (e) Newton, C.
G.; Wang, S. G.; Oliveira, C. C.; Cramer, N. Catalytic
Enantioselective Transformations Involving C–H Bond Cleavage by
Transition-Metal Complexes. Chem. Rev. 2017, 117, 8908−8976. (f)
Song, G.; Li, X. Substrate Activation Strategies in Rhodium(III)-
Catalyzed Selective Functionalization of Arenes. Acc. Chem. Res.
2015, 48, 1007−1020.
(2) For reviews: (a) Gensch, T.; Hopkinson, M. N.; Glorius, F.;
Wencel-Delord, J. Mild metal-catalyzed C−H activation: examples
and concepts. Chem. Soc. Rev. 2016, 45, 2900−2936. (b) Mo, J.;
Wang, L.; Liu, Y.; Cui, X. Transition-Metal-Catalyzed Direct C–H
Functionalization under External Oxidant-Free Conditions. Synthesis
2015, 47, 439−459. (c) Song, G.; Wang, F.; Li, X. C–C, C–O and C–
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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29
30
31
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33
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35
36
37
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41
42
43
44
45
46
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48
49
50
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60
Scale-up synthesis. A seal tube with a stir bar was added
N bond formation via rhodium(III)-catalyzed oxidative C–H
activation. Chem. Soc. Rev. 2012, 41, 3651−3678.
alkynylcyclopropanes
1a
(2.4
mmol,
1.2
eq.),
(3) For selected examples: (a) Wu, Y.; Chen, Z.; Yang, Y.; Zhu, W.;
Zhou, B. Rh(III)-Catalyzed Redox-Neutral Unsymmetrical C–H
Alkylation and Amidation Reactions of N-Phenoxyacetamides. J. Am.
Chem. Soc. 2018, 140, 42−45. (b) Hu, Z.; Tong, X.; Liu, G.
Rhodium(III) Catalyzed Carboamination of Alkenes Triggered by C–
aryloxyacetamides 2a (2.0 mmol, 1 eq.), [RhCp*Cl2]2 (0.10
mmol, 5.0 mol%) and Cu(OAc)2 (1.0 mmol, 0.5 eq.). The tube
was purged three times by vacuum and N2, then the solvent (5
mL, 0.4 M) was added. The mixture was heated to 60 ºC in an
oil bath and stirred for 16 h, which was then concentrated in
vacuum. The residue was purified by silica gel column
chromatography (petroleum ether/ethyl acetate = 5/1 to 1/1) to
give 3a product as white solid in 0.61 g, 75% yield.
H
Activation of N-Phenoxyacetamides under Redox-Neutral
Conditions. Org. Lett. 2016, 18, 1702−1705. (c) Zhou, Z.; Liu, G.;
Chen, Y.; Lu, X. Cascade Synthesis of 3-Alkylidene
Dihydrobenzofuran Derivatives via Rhodium(III)-Catalyzed Redox-
Neutral C–H Functionalization/Cyclization. Org. Lett. 2015, 17,
5874−5877. (d) Zhang, X.; Qi, Z.; Li, X. Rhodium(III)-Catalyzed
C−C and C−O Coupling of Quinoline N–Oxides with Alkynes:
Combination of C–H Activation with O-Atom Transfer. Angew.
Chem., Int. Ed. 2014, 53, 10794−10798. (e) Han, W.; Zhang, G.; Li,
G.; Huang, H. Rh-Catalyzed Sequential Oxidative C–H and N–N
Bond Activation: Conversion of Azines into Isoquinolines with Air at
Room Temperature. Org. Lett. 2014, 16, 3532−3535. (f) Shi, Z.;
Koester, D. C.; Boultadakis-Arapinis, M.; Glorius, F. Rh(III)-
Catalyzed Synthesis of Multisubstituted Isoquinoline and Pyridine N-
Oxides from Oximes and Diazo Compounds. J. Am. Chem. Soc. 2013,
135, 12204−12007. (g) Liu, G.; Shen, Y.; Zhou, Z.; Lu, X.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website.
Copies of 1H and 13C NMR spectra of new compounds and details
of deuterium experiments; NOE spectra of the compound 3a
(PDF).
AUTHOR INFORMATION
Corresponding Author
Rhodium(III)-Catalyzed
Redox-Neutral
Coupling
of
N-
Phenoxyacetamides and Alkynes with Tunable Selectivity. Angew.
Chem., Int. Ed. 2013, 52, 6033−6037.
* E-mail: yanglee@mail.xjtu.edu.cn
silongxu@mail.xjtu.edu.cn
(4) For selected reviews: (a) Mishra, N. K.; Sharma, S.; Park, J.; Han,
S.; Kim, I. S. Recent Advances in Catalytic C(sp2)–H Allylation
Reactions. ACS Catal. 2017, 7, 2821−2847. (b) Wang, F.; Yu, S.; Li,
X. Transition metal-catalysed couplings between arenes and strained
or reactive rings: combination of C–H activation and ring scission.
Chem. Soc. Rev. 2016, 45, 6462−6477.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We thank the National Natural Science Foundation of China (Nos.
21602167, 21871218), the Natural Science Basic Research Plan in
Shaanxi Province of China (Nos. 2016JQ2019, 2015JQ2050), the
China Postdoctoral Science Foundation (Nos. 2015M580830,
2014M550484, 2015T81013), the Fundamental Research Funds
for the Central Universities, and Key Laboratory Construction
Program of Xi'an Municipal Bureau of Science and Technology
(201805056ZD7CG40).
(5) (a) Liang,Y.-F.; Mgller, V.; Liu, W.; Mgnch, A.; Stalke, D.;
Ackermann, L. Methylenecyclopropane Annulation by Manganese(I)-
Catalyzed Stereoselective C–H/C–C Activation. Angew. Chem. Int.
Ed. 2017, 56, 9415–9419. (b) Zhou, X.; Yu, S.; Kong L.; Li, X.
Rhodium(III)-Catalyzed Coupling of Arenes with Cyclopropanols via
C–H Activation and Ring Opening. ACS Catal., 2016, 6, 647–651. (c)
Wu, J.-Q.; Qiu, Z.-P.; Zhang, S.-S.; Liu, J.-G.; Lao, Y-X.; Gu, L.-Q.;
Huang, Z.-S.; Li, J.; Wang, H. Rhodium(III)-Catalyzed C–H/C–C
Activation Sequence: Vinylcyclopropanes as Versatile Synthons in
Direct C–H Allylation Reactions. Chem. Commun., 2015, 51, 77–80.
(d) Zhang, H.; Wang, K.; Wang, B.; Yi, H.; Hu, F.; Li, C.; Zhang Y.;
Wang, J. Rhodium(III)-Catalyzed Transannulation of Cyclopropenes
with N-Phenoxyacetamides through C–H Activation. Angew. Chem.,
Int. Ed., 2014, 53, 13234–13238. (e)Yu S.; Li, X. Mild Synthesis of
Chalcones via Rhodium(III)-Catalyzed C–C Coupling of Arenes and
Cyclopropenones. Org. Lett., 2014, 16, 1220–1233. (f) Cui, S.; Zhang
Y.; Wu, Q. Rh(III)-catalyzed C–H activation/cycloaddition of
benzamides and methylenecyclopropanes: divergence in ring
formation. Chem. Sci., 2013, 4, 3421–3426. (g) Ackermann, L.;
Kozhushkov S. I.; Yufit, D. S. Ruthenium-Catalyzed Hydroarylation
REFERENCES
(1) For recent selected reviews: (a) Gensch, T.; James, M. J.; Dalton,
T.; Glorius, F. Increasing Catalyst Efficiency in C−H Activation
Catalysis. Angew. Chem., Int. Ed. 2018, 57, 2296−2306. (b)
Sambiagio, C.; Schönbauer, D.; Blieck, R.; Dao-Huy, T.; Pototschnig
G.; Schaaf, P.; Wiesinger, T.; Zia, M. F.; Wencel-Delord J.; Besset, T.;
Maes, B. U. W.; Schnürch M. A Comprehensive Overview of
Directing Groups Applied in Metal-catalysed C–H Functionalisation
Chemistry. Chem. Soc. Rev., 2018, 47, 6603−6743. (c) Dong, Z.; Ren,
Z.; Thompson, S. J.; Xu, Y.; Dong, G. Transition-Metal-Catalyzed
C−H Alkylation Using Alkenes. Chem. Rev. 2017, 117, 9333−9403.
8
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Page 9 of 9
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
of Methylenecyclopropanes through CH Bond Cleavage: Scope and
Mechanism. Chem.– Eur. J., 2012, 18, 12068–12077.
goniomitine.. Chem. Eur. J. 2014, 20, 12768−12772. (e) Xu, X.; Liu
Y.; Park, C.-M. Rhodium(III)-Catalyzed Intramolecular Annulation
through C−H Activation: Total Synthesis of (±)-Antofine, (±)-
Septicine, (±)-Tylophorine, and Rosettacin. Angew. Chem., Int. Ed.
2012, 51, 9372−9376.
(14) (a) Chang, X. -H.; Liu, Z. -L.; Luo, Y. -C.; Yang, C.; Liu, X.-
W.; Da, B.-C.; Li, J.-J.; Ahmad, T.; Loh, T.-P.; Xu Y.-H. Copper-
catalyzed silylation reactions of propargyl epoxides: easy access to
2,3-allenols and stereodefined alkenes. Chem. Commun. 2017, 53,
9344−9347. (b) Burke, C. P.; Shi, Y. Enantioselective Epoxidation
of Conjugated cis-Enynes by Chiral Dioxirane. J. Org. Chem. 2007,
72, 4093−4097.
(6) (a) Lu, Q.; Klauck, F. J. R.; Glorius, F. Manganese-catalyzed
allylation via sequential C–H and C–C/C–Het bond activation. Chem.
Sci., 2017, 8, 3379–3383. (b) Meyer, T. H.; Liu, W.; Feldt, M.;
Wuttke, A.; Mata, R. A.; Ackermann, L. Manganese(I)-Catalyzed
Dispersion-Enabled C–H/C–C Activation. Chem. Eur. J. 2017, 23,
5443–5447. (c) Hyster, T. K.; Rovis, T. Rodium(III)-Catalyzed C–H
Activation Mediated Synthesis of Isoquinolones from Amides and
Cyclopropenes. Synlett 2013, 24, 1842–1844. (d) Matsuda, T.; Suda
Y.; Takahashi, A. Double 1,4-rhodium migration cascade in rhodium-
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
catalysed
arylative
ring-opening/spirocyclisation
of
(3-
arylcyclobutylidene)acetates. Chem. Commun., 2012, 48, 2988–2990.
(e) Seiser, T.; Roth, O. A.; Cramer, N. Enantioselective Synthesis of
Indanols from tert-Cyclobutanols Using a Rhodium-Catalyzed C–
C/C–H Activation Sequence. Angew. Chem., Int. Ed., 2009, 48,
6320–6323.
(7) For a review: Schneider, T. F.; Kaschel, J. Werz, D. B. A New
Golden Age for Donor-Acceptor Cyclopropanes. Angew. Chem. Int.
Ed. 2014, 53, 5504–5523.
(15) Preindl, J.; Chakrabarty, S.; Waser J. Dearomatization of
Electron Poor Six-membered N-heterocycles Through [3+2]
Annulation with Aminocyclopropanes. Chem. Sci., 2017, 8, 7112–
7118.
(16) Petrassi, H. M.; Sharpless, K. B.; Kelly, J. W. The Copper-
Mediated Cross-Coupling of Phenylboronic Acids and N-
Hydroxyphthalimide at Room Temperature:ꢀ Synthesis of
Aryloxyamines. Org. Lett. 2001, 3, 139−142.
(8) (a) Li, Y.; Xu, S. Transition–Metal–Catalyzed C−H
Functionalization for Construction of Quaternary Carbon Centers.
Chem. Eur. J. 2018, 24, 16218−16245. (b) Wei, W.; Tang, Y.; Zhou,
Y.; Deng, G.; Liu, Z.; Wu, J.; Li, Y.; Zhang, J.; Xu, S. Recycling
Catalyst as Reactant: A Sustainable Strategy To Improve Atom
Efficiency of Organocatalytic Tandem Reactions. Org. Lett. 2018, 20,
6559–6563. (c) Li, Y.; Shi, D.; Tang, Y.; He, X.; Xu, S.
Rhodium(III)-Catalyzed Redox-Neutral C–H Activation/Annulation
of N-Aryloxyacetamides with Alkynyloxiranes: Synthesis of Highly
Functionalized 2,3-Dihydrobenzofurans. J. Org. Chem. 2018, 83,
9464–9470. (d) Wu, J.; Tang, Y.; Wei, W.; Wu, Y.; Li, Y.; Zhang, J.;
Zheng, Y.; Xu, S. Phosphine-Catalyzed Activation of
Vinylcyclopropanes: Rearrangement of Vinylcyclopropylketones to
Cycloheptenones. Angew. Chem., Int. Ed. 2018, 57, 6284−6288. (e)
Zhang, J.; Tang, Y.; Wei, W.; Wu, Y.; Li, Y.; Zhang, J.; Zheng, Y.;
Xu, S. Organocatalytic Cloke-Wilson Rearrangement: DABCO-
Catalyzed Ring Expansion of Cyclopropyl Ketones to 2,3-
Dihydrofurans. Org. Lett. 2017, 19, 3043−3046; (f) Li, Y.; Tang, Y.;
He, X.; Shi, D.; Wu, J.; Xu S. Rhodium(III)-Catalyzed Annulative
Carbooxygenation of 1,1-Disubstituted Alkenes Triggered by C–H
Activation. Chem. Eur. J. 2017, 23, 7453−7457.
(17) In another pathway (see below), ring contraction of rhodacycle
II generates RhV species III' which, upon the additon of AcOH,
undergoes reductive elimination to afford product 3a and recycle the
catalyst.
CO2Me
MeO2C
MeO2C
CO2Me
CO2Me
MeO2C
Cp*Rh(OAc)2
AcOH
AcOH
3a
RE
Ph
Ph
Ph
O
O
O
*CpRhIII
III'
RhvCp* IV'
RhvCp*
N
AcO
AcO NHAc
AcO
II
Ac
NAc
(9) For
a
review on transition metal–catalyzed C−H
functionalization for construction of quaternary carbon centers , see
ref 8a.
(10) Reaction conditions for those with low yields were rescreened,
and CsOAc was found to give better yields. So we used CsOAc
instead of Cu(OAc)2 in those substrates.
(11) For selected reviews: (a) Marco-Contelles, J.; Carreiras, M.; do,
C.; Rodrιǵ uez, C.; Villarroya, M.; Garcιá , A. G. Synthesis and
Pharmacology of Galantamine. Chem. Rev. 2006, 106, 116−133. (b)
Proksch, P.; Rodriguez, E. Chromenes and benzofurans of the
asteraceae,
their
chemistry
and
biological
significance.
Phytochemistry 1983, 22, 2335−2348.
(12) Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Ligand-Accelerated C-H
Activation Reactions: Evidence for a Switch of Mechanism. J. Am.
Chem. Soc. 2010, 132, 14137−14151.
(13) (a) Sen, M.; Dahiya, P.; Premkumar, J. R.; Sundararaju, B.
Dehydrative Cp*Co(III)-Catalyzed C−H Bond Allenylation. Org. Lett.
2017, 19, 3699−3702. (b) Lu, Q.; Greßies, S.; Cembellιń , S.; Klauck,
F. J. R.; Daniliuc, C. G.; Glorius, F. Redox-Neutral Manganese(I)-
Catalyzed C−H Activation: Traceless Directing Group Enabled
Regioselective Annulation. Angew. Chem., Int. Ed. 2017, 56,
12778−12782. (c) Wu, S.; Huang, X.; Wu, W.; Li, P.; Fu, C.; Ma, S.
A C−H Bond Activation-based Catalytic Approach to Tetrasubstituted
Chiral Allenes. Nat. Commun. 2015, 6, 7946. (d) Zhou, B.; Du, J.;
Yang Y.; Li, Y. Rhodium(III)-catalyzed intramolecular redox-neutral
annulation of tethered alkynes: formal total synthesis of (±)-
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