Redox-Neutral Annulation of Alkynylcyclopropanes with N

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Redox-Neutral Annulation of Alkynylcyclopropanes with Naryloxyamides 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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The Journal of Organic Chemistry

Redox-Neutral Annulation of Alkynylcyclopropanes with Naryloxyamides 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* 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

R3 R2

EWG

1

[Cp*RhCl2]2 (5 mol%)

NHR1

Cu(OAc)2 (50 mol%) MeOH, 60 °C

+ O

H 2

EWG

3 NHR1

R

2

O

R3

 redox neutral  regioselective  E-selective  35-76% yields  24 examples

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 metalcatalyzed 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. 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

C−H activation and cyclopropane chemistry,8 we report a Cp*RhIII-catalyzed regioselective annulation of alkynylcyclopropanes 1 with N-aryloxyamides 2 via redoxneutral 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

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Previous reported DG

strained carbocycles

R

R'

R

C-H & C-C activation /annulation products

[TM]

H

R'

EWG

EWG

R OH

O R Ph

R'

R This work EWG

R3

R' OH O

EWG

R2

R'

Ph R

EWG

NHR1

2

EWG

[Cp*RhCl2]2 (5 mol%)

3

Cu(OAc)2 (50 mol%) MeOH, 60 C, 16 h

NHR1

1

R2

R3

O

Initially, the reaction of dimethyl 2(phenylethynyl)cyclopropane-1,1-dicarboxylate (1a) with Nphenoxyacetamide (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 1. Optimization of Reaction O MeO2C

Ph

entry 1 2 3 4 5 6

CO2Me

1a

catalyst [RhCp*Cl2]2 [IrCp*Cl2]2 [RuCl2(p-cymene)]2 Pd(OAc)2 [RhCp*Cl2]2 [RhCp*Cl2]2

7 [RhCp*Cl2]2 PhMe CsOAc 15 8 [RhCp*Cl2]2 dioxane CsOAc 11 9 [RhCp*Cl2]2 CH3CN CsOAc 38 10c [RhCp*Cl2]2 MeOH CsOAc 54 11d [RhCp*Cl2]2 MeOH CsOAc 57 12 [RhCp*Cl2]2 MeOH KOAc 59 13 [RhCp*Cl2]2 MeOH NaOAc 46 14 [RhCp*Cl2]2 MeOH AgOAc 63 15 [RhCp*Cl2]2 MeOH Cu(OAc)2 68 16e [RhCp*Cl2]2 MeOH Cu(OAc)2 53 17f [RhCp*Cl2]2 MeOH Cu(OAc)2 74 18g [RhCp*Cl2]2 MeOH Cu(OAc)2 65 19h [RhCp*Cl2]2 MeOH Cu(OAc)2 68 20f,i [RhCp*Cl2]2 MeOH Cu(OAc)2 76 a Unless specified, the reactions were carried out under N using 2 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. b Isolated yields. c 1.0 eq. CsOAc was used. d 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.

Table 2. Substrate Scopea O

CO2Me

solvent MeOH MeOH MeOH MeOH THF DCE

additive CsOAc CsOAc CsOAc CsOAc CsOAc CsOAc

57 trace trace trace 9 14

CO2Me

NHAc NHAc O

Me

Ph

3j: R2 = Me, 75%c 3k: R2 = OMe, 58%c

Ph

O 3l: 36%c

CO2Me MeO2C

CO2Me O

3s: R = 4-MePh, 60% 3t: R3 = 4-BrPh, 66%

R3

3m: R3 = 4-MePh, 63%c 3n: R3 = 4-OMePh, 67%c 3o: R3 = 4-FPh, 59%c

MeO2C Br

CO2Me

3p: R3 = 4-ClPh, 55%c

(%)

3

3r: R = 3-MePh, 53%

c

3e: R2 = tBu, 42% 3g: R2 = Cl, 47%c 3h: R2 = Br, 48% 3i: R2 = CF3, 41%

MeO2C F

CO2Me

NHAc O

O 3

3u: R = 4-MePh, 48% 3v: R3 = 4-OMePh, 56%

MeO2C Me

CO2Me

NHAc

R3

3w: R = 4-ClPh, 35%

R3

3

NHAc

3q: R3 = 4-BrPh, 69%c

Ph

3d: R2 = Me, 57%

R3

3

NHAc

NHAc O

NHAc

Me

MeO2C

O

CO2Me

3f: R2 = F, 52%

MeO2C

MeO2C

NHAc Ph

yieldb

MeO2C R2

Ph O 3c, 66%c

3a: R1 = Ac, 76% (75%)b 3b: R1 = Piv, 48%c

R

R3

O

NHAc

Ph

2

R2

CO2Et EtO2C

NHR1

3a O

3 NHR1

CO2Me

MeO2C

conditions

EWG

Cu(OAc)2 (50 mol%) MeOH, 60 C, 16 h

MeO2C

O

EWG

NHR1

2

[Cp*RhCl2]2 (5 mol%) 1

R3

Conditionsa

NHAc

R2

EWG

EWG

CO2Me

2a

Page 2 of 9

O

R3

3

3x: R = 4-BrPh, 40%

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 25 mL Schlenk tube at 60 ºC for 16 h. b Yield of 2 mmol scale. c

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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 Nphenoxyacetamide 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 Naryloxyacetamides with alkynylcyclopropanes offers a mild redox-neutral synthesis of highly functionalized 2,3dihydrobenzofurans, 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 dihydrofurans 3 was well identified by 1H, 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 3. Proposed Mechanism

Scheme 2. Mechanistic Studies 1c

+

2a

O H5/D5 2a/2a-d5

NHAc

[Cp*RhCl2]2 (5 mol%) Cu(OAc)2 (50 mol%) CD3OD, 60 C, 1 h 1c [Cp*RhCl2]2 (5 mol%)

3n 60% yield, no deuterium incorporation

(a)

CO2Me MeO2C

Cu(OAc)2 (50 mol%) NHAc CD3OD, 60 °C, 1 h H4/D4 4-OMePh O kH/D = 1.05 3n/3n-d4

(b)

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

NHAc Cu(OAc)2

2a

C-H activation O

1a

2 AcOH O *Cp RhIII N O Ph

migratory insertion O O N RhIIICp*

oxidative addition O

Ph II MeO2C

CO2Me

3a

CO2Me CO2Me

protonolysis

NAc RhIII I Cp*

Ph

CO2Me

Ph V

Cp*Rh(OAc)2

2 AcOH

CO2Me

OH NHAc S 2' N

1/2 [Cp*RhCl2]2

O

reductive elimination

MeO2C

N

O

IV

CO2Me CO2Me

[RhICp*]

Ph

III CO2Me

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 5membered rhodacycle intermediate I. A regioselective migratory insertion of I into the alkyne of 1a forms a 7membered 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 7membered 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 2,3dihydrobenzofurans 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.

EXPERIMENTAL SECTION General Methods. All reactions and manipulations involving air-sensitive compounds were performed using standard Schlenk techniques. Anhydrous THF and dioxane



were distilled from sodium. Anhydrous CH2Cl2 were distilled from CaH2 under an atmosphere of N2. Anhydrous MeOH was distilled from magnesium under N2 atmosphere. 1H, 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. 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-(phenylethynyl)cyclopropane-1,1-dicarboxylate, (1a). Colorless liquid, yield 619 mg (80%); 1H 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. Diethyl 2-(phenylethynyl)cyclopropane-1,1-dicarboxylate, (1a'). Colorless liquid, yield 700 mg (80%); 1H NMR (400 MHz, CDCl3) δ = 7.36-7.33 (m, 2H), 7.28-7.24 (m, 3H), 4.304.16 (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. Dimethyl 2-(p-tolylethynyl)cyclopropane-1,1-dicarboxylate, (1b). Colorless liquid, yield 645 mg (79%); 1H 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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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. Dimethyl 2-((4-methoxyphenyl)ethynyl)cyclopropane-1,1dicarboxylate, (1c). Colorless liquid, yield 700mg (81%); 1H 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. Dimethyl 2-((4-fluorophenyl)ethynyl)cyclopropane-1,1dicarboxylate, (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, CDCl ) δ = 169.0, 166.8, 162.4 (d, 3 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-1,1dicarboxylate, (1e). Colorless liquid, yield 657 mg (75%); 1H 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-((4-bromophenyl)ethynyl)cyclopropane-1,1dicarboxylate, (1f). Colorless liquid, yield 766mg (76%); 1H 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, CDCl ) δ = 169.0, 166.8, 133.2, 3 131.6, 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. Dimethyl2-(m-tolylethynyl)cyclopropane-1,1-dicarboxylate, (1g). Colorless liquid, yield 498 mg (61%); 1H 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,


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138.0, 132.3, 129.2, 128.9, 128.2, 122.5, 84.9, 80.7, 53.1, 53.0, 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. 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 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-2-phenylbenzofuran3(2H)-ylidene)ethyl)malonate, (3a). White solid, yield 62 mg (76%); M.p. = 183-184 °C; 1H 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-phenyl-2-pivalamidobenzofuran3(2H)-ylidene)ethyl)malonate, (3b). White solid, yield 44 mg (48%); M.p. = 101-103 °C; 1H 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. 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-

TOF) m/z: [M+H]+Calcd for C25H28NO6 438.1911; Found 438.1911. Dimethyl (E)-2-(2-(2-acetamido-5-methyl-2-phenylbenzofuran-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. Dimethyl (E)-2-(2-(2-acetamido-5-(tert-butyl)-2-phenylbenzofuran-3(2H)-ylidene) ethyl) malonate, (3e). White solid, yield 40 mg (42%); M.p. = 116-117 °C; 1H 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, DMSOd6) 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-5-fluoro-2-phenylbenzofuran-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-acetamido-5-chloro-2-phenylbenzofuran-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), 7.427.30 (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.



Dimethyl (E)-2-(2-(2-acetamido-5-bromo-2-phenylbenzofuran-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. Dimethyl (E)-2-(2-(2-acetamido-2-phenyl-5-(trifluoromethyl)benzofuran-3(2H)-ylidene)ethyl)malonate,(3i). White solid, yield 40 mg (41%); M.p. = 161-162°C; 1H NMR (400 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-6-methyl-2-phenylbenzofuran-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. Dimethyl (E)-2-(2-(2-acetamido-6-methoxy-2-phenylbenzofuran-3(2H)-ylidene)ethyl)malonate, (3k). White solid, yield 51 mg (58%); M.p. = 146-147 °C; 1H 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-phenylbenzofuran-3(2H)-ylidene)ethyl)malonate, (3l). White solid, yield

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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 (ESITOF) m/z: [M+Na]+Calcd for C24H25NNaO6 446.1574; Found 446.1572. Dimethyl (E)-2-(2-(2-acetamido-2-(p-tolyl)benzofuran3(2H)-ylidene)ethyl)malonate, (3m). White solid, yield 54 mg (63%); M.p. = 186-187 °C; 1H NMR (400 MHz, DMSO-d6) δ = 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), 2.992.80 (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. Dimethyl (E)-2-(2-(2-acetamido-2-(4-methoxyphenyl)benzofuran-3(2H)-ylidene)ethyl)malonate, (3n). White solid, yield 59 mg (67%); M.p. = 150-151 °C; 1H NMR (400 MHz, 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)benzofuran-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-2-(4-chlorophenyl)benzofuran-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, 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. Dimethyl (E)-2-(2-(2-acetamido-2-(4-bromophenyl)benzofuran-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)benzofuran3(2H)-ylidene)ethyl)malonate, (3r). White solid, yield 45 mg (53%); M.p. = 187-188 °C; 1H NMR (400 MHz, DMSO-d6) δ = 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, DMSOd6) 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. Dimethyl (E)-2-(2-(2-acetamido-6-methyl-2-(p-tolyl)benzofuran-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-2-(4-bromophenyl)-6-methylbenzofuran-3(2H)-ylidene)ethyl)malonate, (3t). White solid, yield 66 mg (66%); M.p. = 184-185 °C; 1H NMR (400 MHz, DMSO-d6) δ = 8.89 (s, 1H), 7.54 (d, J = 8.6 Hz, 2H),

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 cm-1; HRMS (ESI-TOF) m/z: [M+K]+Calcd for C24H24BrKNO6 540.0419; Found 540.0414. Dimethyl (E)-2-(2-(2-acetamido-5-fluoro-2-(p-tolyl)benzofuran-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-5-fluoro-2-(4-methoxyphenyl)benzofuran-3(2H)-ylidene)ethyl)malonate, (3v). 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-5-bromo-2-(4-chlorophenyl)benzofuran-3(2H)-ylidene)ethyl)malonate, (3w). 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)-5methylbenzofuran-3(2H)-ylidene)ethyl)malonate, (3x). White



solid, yield 40 mg (40%); M.p. = 200-201 °C; 1H 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, DMSOd6) 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. Scale-up synthesis. A seal tube with a stir bar was added alkynylcyclopropanes 1a (2.4 mmol, 1.2 eq.), 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.

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 * E-mail: [email protected] [email protected] 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).

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.

Page 8 of 9

(d) Hummel, J. R.; Boerth, J. A.; Ellman, J. A. Transition-MetalCatalyzed 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– N bond formation via rhodium(III)-catalyzed oxidative C–H activation. Chem. Soc. Rev. 2012, 41, 3651−3678. (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– 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 RedoxNeutral 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 NOxides from Oximes and Diazo Compounds. J. Am. Chem. Soc. 2013, 135, 12204−12007. (g) Liu, G.; Shen, Y.; Zhou, Z.; Lu, X. Rhodium(III)-Catalyzed Redox-Neutral Coupling of NPhenoxyacetamides and Alkynes with Tunable Selectivity. Angew. Chem., Int. Ed. 2013, 52, 6033−6037. (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. (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


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of Methylenecyclopropanes through CH Bond Cleavage: Scope and Mechanism. Chem.– Eur. J., 2012, 18, 12068–12077. (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 rhodiumcatalysed arylative ring-opening/spirocyclisation of (3arylcyclobutylidene)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. (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: DABCOCatalyzed Ring Expansion of Cyclopropyl Ketones to 2,3Dihydrofurans. 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. (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 (±)-

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. Coppercatalyzed 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. (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 CopperMediated Cross-Coupling of Phenylboronic Acids and NHydroxyphthalimide at Room Temperature: Synthesis of Aryloxyamines. Org. Lett. 2001, 3, 139−142. (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

Ph *CpRhIII

MeO2C

CO2Me

AcOH O

N II Ac

MeO2C

CO2Me Cp*Rh(OAc)2

AcOH Ph O AcO RhvCp* III' NAc

Ph O AcO RhvCp* IV' AcO NHAc

RE

3a


Redox-Neutral Annulation of Alkynylcyclopropanes with N

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