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Sep 12, 2017 - Regio- and Diastereoselective Construction of Spirocyclopenteneoxindoles through Phosphine-Catalyzed [3 + 2] Annulation of ...
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Regio- and Diastereoselective Construction of Spirocyclopenteneoxindoles through Phosphine-Catalyzed [3 + 2] Annulation of Methyleneindolinone with Alkynoate Derivatives Jiayong Zhang,† Cheng Cheng,† Dian Wang,† and Zhiwei Miao*,†,‡ †

State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Weijin Road 94, Tianjin 300071, China ‡ Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China S Supporting Information *

ABSTRACT: A phosphine-catalyzed [3 + 2] annulation of isatin-derived α,β-unsaturated ketones with alkynoates for the synthesis of cyclopentene spiro-oxindole skeletons has been developed. This reaction afforded the desired products in high to excellent yields (up to 99%) with high regioselectivity and moderate to high diastereoselectivities (up to 20:1). This strategy allows facile diastereoselective preparation of biologically important spiro-(cyclopentene) oxindoles containing three contiguous stereocenters, including the quaternary stereogenic center joining the two rings.

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INTRODUCTION The regioselective and stereoselective preparation of biologically relevant spirooxindoles, which contain a tetrasubstituted carbon stereocenter at the C-3 position, is challenging and has led to a demand for efficient methods for their synthesis.1 Among the family of spirooxindoles, the spirooxindoles with carbocyclic five-membered rings behave a key pharmacophore in many bioactive natural products, such as citrinadins,2 cycloplamines,3 versicolamides, and notoamides,4 as well as in synthetic bioactive compounds.5 Consequently, much effort aimed toward identifying general methods for the synthesis of these spirocyclopentene oxindole scaffolds has been made.6 The challenging point is that biologically relevant spirooxindoles often display a stereogenic all-carbon quaternary center at the C3-position, the stereochemistry of which must be controlled through appropriate synthetic strategies.7 Considering the intriguing molecular architecture and potent biological activities, various protocols have been developed to synthesize this class of molecules. However, the diastereoselective synthesis of five-membered spirooxindole, especially functionalized all-carbon spirocyclopentene oxindole containing three contiguous stereocenters still remains a challenging task.8 In 2013, Marinetti and Voituriez developed the phosphinepromoted synthesis of 3,3-spirocyclopenteneoxindoles by [3 + 2] annulations between γ-substituted allenoates and arylideneoxindoles (Scheme 1, a).9 Huang and co-workers described a phosphine-catalyzed Rauhut−Currier domino reaction of conjugated diene with methyleneindolinones for the synthesis of carbocyclic spirooxindoles (Scheme 1, b).10 Even though many phosphine-involved reactions have been discovered, few efforts so far have been focused on the strategy for spiro-fused penteneoxindole framworks employing alkynoate derivatives as substrates.11 Recently, a nucleophilic-phosphine-catalyzed © 2017 American Chemical Society

annulation of electron-deficient alkynes has emerged as a powerful tool for the construction of various biologically active carbocycles12 and heterocycles13 containing spiro-oxindole skeletons. We have recently reported the regio- and stereocontrolled synthesis of cyclopentene-fused spiro-rhodanines through phosphine-catalyzed [3 + 2] cycloaddition of alkynoate derivatives with 5-arylidene-3-tert-butyl-2-thioxothiazolidin-4ones (Scheme 1, c).14 Inspired by our previous studies on the use of alkynoate derivatives in the [3 + 2] cycloaddition reaction, in this report, we describe phosphine-catalyzed highly diastereoselective [3 + 2] cycloaddition between 5-arylpent-2ynoates and methyleneindolinones in the synthesis of cyclopentene-fused spiro-oxindole skeletons. This methodology led to molecules containing three contiguous stereocenters, including one spiro quaternary carbon center, in good to excellent yields and stereoselectivities with up to >20:1 diastereomeric ratio (dr).

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RESULT AND DISCUSSION

We initiated our investigation by evaluating the reaction of ethyl 5-phenylpent-2-ynoate 1a and (Z)-methyleneindolinone 2a with toluene as the solvent in the presence of 20 mol % of triphenylphosphine (PPh3) at room temperature (Table 1, entry 1). Unexpectedly, triphenylphosphine failed to catalyze the reaction. No product was obtained after 24 h, and 1a was completely recovered. We assumed that the lack of reaction was due to the weak nucleophilic ability of the phosphine. Therefore, we turned our attention to more active phosphine catalysts (Table 1, entries 2−6). With sterically bulky methyldiphenylphosphine (Ph2PMe) as the catalyst, the desired Received: June 26, 2017 Published: September 12, 2017 10121

DOI: 10.1021/acs.joc.7b01582 J. Org. Chem. 2017, 82, 10121−10128

Article

The Journal of Organic Chemistry Scheme 1. Previous and Proposed Work

(Bu3P) emerged as the preferred catalyst in terms of yield and diastereoselectivity (Table 1, entries 3−6). This result, in line with the nucleophilicity of the phosphines, showed that the efficiency of formation of these skeletons is highly catalystdependent. Subsequently, solvent effects were investigated for this reaction. Various solvents, such as THF, DCM, MeCN, and methyl tert-butyl ether (MTBE), were scanned, but no better results could be obtained (Table 1, entries 7−10), nor did toluene lead to a satisfactory yield and diastereoselectivity. Further studies suggested that reduced reaction time disfavored this reaction, and when the reaction time was shortened to 12 h, the reaction yield decreased to 82% with 8:1 dr (Table 1, entry 11). Decreasing the loading of catalyst and the reaction temperature led to a decrease of the diastereoselectivities and yields (Table 1, entries 12 and 13). Finally, we confirmed the optimal reaction conditions for this transformation as 0.15 mmol of ethyl 5-phenylpent-2-ynoate 1a, 0.10 mmol of (Z)methyleneindolinone 2a, and 20 mol % of PBu3 as a catalyst in 1 mL of toluene as a solvent at room temperature. The diastereomeric ratio of product was determined by 1H NMR spectroscopy of the crude product. In order to determine the relative configuration of the major diastereomer 3a, a singlecrystal X-ray diffraction study of 3a was performed (see the details in the Supporting Information).15 The molecular structure of 3a showed that the relative configuration of the main product was assigned as threo. We then examined the scope and limitations of this reaction between alkynoate derivatives 1 and diversified (Z)-methyleneindolinones 2. In the case of compound 2, either bearing a neutral, electron-withdrawing, or electron-donating group at the 5-, 6-, or 7-position of the benzene ring of N-methylisatins, the reactions proceeded smoothly to give cyclopentene 4-spirooxindoles 3 in good to excellent yields with moderate to excellent diastereoselectivities (Table 2). However, when the

Table 1. Optimization of Conditions of the [3 + 2] Cycloaddition of 1a and 2aa

entry

catalyst

solvent

time (h)

drb

yieldc (%)

1 2 3 4 5 6 7 8 9 10 11 12g 13h

PPh3 Ph2PMe Ph2PEt PBu3 DPPPd DPPBe PBu3 PBu3 PBu3 PBu3 PBu3 PBu3 PBu3

toluene toluene toluene toluene toluene toluene THF DCM MeCN MTBEf toluene toluene toluene

24 24 24 24 24 24 24 24 24 24 12 24 24

− 8:1 7:1 9:1 6:1 6:1 6:1 5:1 5:1 6:1 8:1 8:1 9:1

− 43 57 93 52 61 73 51 59 37 82 53 42

a

Unless otherwise specified, all reactions were carried out using ethyl 5-phenylpent-2-ynoate 1a (0.15 mmol) and (Z)-methyleneindolinone 2a (0.10 mmol) in 1 mL of solvent with 20 mol % of catalyst at room temperature. bDiastereomeric ratio (dr) values were determined by 1H NMR of crude products. cYield of isolated product of 3a after column chromatography. dDPPP = 1,3-bis(diphenylphosphino)propane. e DPPB = 1,3-bis(diphenylphosphino)butane. fMTBE = methyl tertbutyl ether. g10% PBu3 was used. hThe temperature of the reaction was reduced to 0 °C.

cycloaddition product 3a was obtained in 43% yield with moderate diastereoselectivity (8:1 dr) (Table 1, entry 2). The result inspired us and demonstrated that our design is feasible. In the screening of phosphine catalysts, tributylphosphine 10122

DOI: 10.1021/acs.joc.7b01582 J. Org. Chem. 2017, 82, 10121−10128

Article

The Journal of Organic Chemistry Table 2. Substrate Scope of the Reactiona

entry

product

R1

R2

R3

R4

R5

drb

yieldc (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

3a 3b 3c 3d 3e 3f 3g 3h 3i 3j 3k 3l 3m 3n 3o 3p 3q 3r 3s 3t 3u

Et Et Et Et Bn Bn Et Bn Et Me Me Et Bn Me Et Et Et Bn Et Bn Et

Bn (1a) Bn (1a) Me (1b) Bn (1a) Bn (1c) Bn (1c) Bn (1a) Bn (1c) H (1d) Bn (1e) Bn (1e) Me (1b) Bn (1c) Bn (1e) Me (1b) Me (1b) Bn (1a) Bn (1c) Bn (1a) Bn (1c) H (1d)

Et Me t Bu Et Et Et t Bu t Bu Me Et Me Et Me Et Et Et Et Et t Bu t Bu Et

H 5-Br 5-Cl 5-Me 5-Br 6-OMe 6-OMe 6-OMe 6-OMe 6-OMe 6-OMe 6-OMe 7-Me 7-Me 5-Me 5-NO2 5-Cl H H H H

Me (2a) Me (2b) Me (2c) Me (2d) Me (2e) Me (2f) Me (2g) Me (2g) Me (2h) Me (2f) Me (2h) Me (2f) Me (2i) Me (2j) Me (2d) Me (2k) Me (2l) Me (2a) Bn (2m) Bn (2m) Me (2a)

9:1 >20:1 >20:1 >20:1 >20:1 >20:1 >20:1 >20:1 >20:1 16:1 10:1 8:1 8:1 6:1 6:1 4:1 2:1 8:1 8:1 12:1 >20:1

93 87 76 91 86 99 97 87 91 93 83 95 96 87 82 69 79 86 91 85 86

a

Reaction conditions: alkynoate 1 (0.15 mmol), methyleneindolinones 2 (0.10 mmol) in 1 mL of toluene at room temperature in the presence of 20 mol % of PBu3. bDiastereomeric ratio (dr) values were determined by 1H NMR of crude products. cIsolated yield after silica gel chromatography of 3.

substituent was at the 5-position with an electron-withdrawing group of the benzene ring of N-methylisatin 2k and 2l, the spiro compounds 3p and 3q were obtained in somewhat lower yields with lower diastereoselectivities (Table 2, entries 16 and 17). Furthermore, it was observed that the steric hindrance of the ester substituent of (Z)-methyleneindolinones 2 has no effect on the result (Table 2, entries 6−8). Exchanging the Nprotecting group with Bn also gave the cyclic adducts in good yields with moderate diastereoselectivities (Table 2, entries 19 and 20). Finally, selected alkynoates 1 were further examined in the cycloaddition reaction with representative (Z)-methyleneindolinones 2. The substituents in the alkynoates 1 were well tolerated, leading to formation of desired products in good yields and moderate diastereoselectivities (Table 2, entries 12− 20). We were delighted to find that the aliphatic substituted alkynoate derivative, ethyl but-2-ynoate (1d), underwent smooth sequential annulations with 2h and 2a, respectively, to give the corresponding products (i.e., 3i and 3u) in good yields with excellent diastereoselectivities (Table 2, entries 9 and 21). The regiochemical outcome of this reaction may be rationalized as depicted in Scheme 2. On the basis of steric considerations, this [3 + 2] cycloaddition reaction can take place via the transition state TS I, which would be expected to be favored over the more sterically demanding transition state TS II. Thus, we obtained regioisomer A as our product. In order to gain insight into the influences the product stereochemical outcome of this reaction, we carried out one

Scheme 2. Targeted Approach to Regioselectivitive Synthesis of Cyclopentene 5-Spiro-oxindole 3a

control experiment (Scheme 3). Under the identified conditions, treatment of ethyl 5-phenylpent-2-ynoate 1a with (E)-methylideneoxindole 2a′ in the presence of 20 mol % of PBu3 furnished the cyclopentane 4-spiro-oxindole 3a′ in 86% yield with 8:1 dr. This result suggested that the starting material 10123

DOI: 10.1021/acs.joc.7b01582 J. Org. Chem. 2017, 82, 10121−10128

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The Journal of Organic Chemistry

product 3a has not been determined) (Table 3, entry 6). However, with P6 as chiral catalyst, the attempt to improve the enantioselectivity by decreasing the reaction temperature to 0 °C failed, only affording the cycloaddition product in 49% yield and 53% ee (Table 3, entry 7). Increasing the reaction temperature to 60 °C leads to a higher yield with excellent diastereoselectivity and 58% ee (Table 3, entry 8). The mechanism of this [3 + 2] annulation reaction is proposed on the basis of previous literature16 as shown in Scheme 4. The catalyst phosphine as a nucleophile reacts with ethyl 5-phenylpent-2-ynoate 1a to produce the zwitterionic intermediate A, which can isomerize to intermediate B. Intermediate B subsequently undergoes a Michael addition to generate the intermediate C, which further undergoes an intramolecular cyclization to furnish the phosphorene D. Intermediate D can be converted to intermediate E via an Hshift. Releasing the phosphine, the products 3 are finally furnished. The reaction rate and diastereoselective product distribution of 3 are attributed to the steric hindrance effects and electronic repulsions between benzyl group of alkynoate and tributylphosphonium.

Scheme 3. Control Experiment for the Synthesis of Cyclopentene 5-Spiro-oxindole 3a′

alkyleneindolinone 2 cannot determine the product 3 stereochemical outcome. Preliminary studies on the asymmetric variant of this phosphine-catalyzed [3 + 2] annulation between methyleneindolinone and alkynoate derivatives were also investigated by employing several chiral phosphines as catalyst. The [3 + 2] annulation of ethyl 5-phenylpent-2-ynoate 1a with ethyl (Z)-2(1-methyl-2-methyleneindolin-3-ylidene) acetate 2a was selected as a model reaction (Table 3). The chiral bifunctional Table 3. Screening of the Reaction Conditions for an Asymmetric Varianta

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CONCLUSION In conclusion, we developed an efficient phosphine-catalyzed diastereoselective [3 + 2] cycloaddition of alkynoate derivatives with (Z)-methyleneindolinone, affording the functionalized 5spiro-cyclopenteneoxindole derivatives in good to excellent yields, with high regioselectivities and diastereoselectivities. Two new C−C bonds together with three contiguous stereocenters, including one spiro quaternary chiral center, were formed. Further studies on the reactions of activated alkynoate derivatives to complex molecular synthesis are currently underway in our laboratory and will be reported in due course.

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entry

catalyst

T (°C)

yieldb (%)

drc (%)

eed (%)

1 2 3 4 5 6 7 8

P1 P2 P3 P4 P5 P6 P6 P6

rt rt rt rt rt rt 0 60

43 − − − − 73 49 92

11:1 − − − − 98:2 95:5 >99:1

5 − − − − 59 53 58

EXPERIMENTAL SECTION

General Methods. All reactions were performed under N2 atmosphere in oven-dried glassware with magnetic stirring. Solvents were dried and distilled prior to use according to the standard methods. Unless otherwise indicated, all materials were obtained from commercial sources and used as purchased without dehydration. Flash column chromatography was performed on silica gel (particle size 10− 40 μm, Ocean Chemical Factory of Qingdao, China). Nitrogen gas (99.999%) was purchased from Boc Gas, Inc. 1H NMR and 13C NMR spectra were recorded in CDCl3 on Bruker 400 MHz spectrometers, and TMS served as internal standard (δ = 0 ppm) for 1H NMR and 13 C NMR. The crystal structure was determined on a Bruker SMART 1000 CCD diffractometer. Mass spectra were obtained using an electrospray ionization (ESI-TOF) mass spectrometer. Optical rotations were taken on a digital polarimeter. Enantiomeric excesses were determined using an HPLC instrument with Chiralpak columns as noted. Experimental Methods. General Procedure for Formal [3 + 2] Cycloaddition Reaction for Products 3. Under a nitrogen atmosphere, to a mixture of (Z)-methyleneindolinones 2 (0.1 mmol, 1.0 equiv) and Bu3P (4.1 mg, 0.02 mmol, 20 mmol %) was added toluene (1 mL) via a syringe and the resulting mixture allowed to stir for 5 min at room temperature. Alkynoates 1 (0.15 mmol, 1.5 equiv) were added, and the reaction was allowed to stir for 24 h at room temperature. The reaction was monitored by TLC. After the reaction was completed, the reaction mixture was directly purified by flash column chromatography (eluted with 20:1 petroleum ether/EtOAc) to afford the product 3. Diethyl 5-Benzyl-1′-methyl-2′-oxospiro[cyclopent[3]ene-1,3′-indoline]-2,3-dicarboxylate (3a). Yellow oil (40.3 mg, 93% yield). [α]D25 = +15 (c = 1.0, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ 7.29

a

Unless otherwise specified, all reactions were carried out with 1a (0.15 mmol) and 2a (0.10 mmol) in the presence of 20 mol % of chiral catalyst in 1.0 mL of toluene at room temperature. bYield of isolated product of 3a after column chromatography. cDiastereomeric ratio (dr) values were determined by 1H NMR of crude products. d Determined by chiral HPLC analysis.

catalyst P1 demonstrated good diastereoselective but poor enantioselective catalytic capability (Table 3, entry 1). Subsequent examination of several chiral bisphosphines (P2− P5) showed that the desired [3 + 2] annulation products could not be obtained, and only starting materials were recovered (Table 2, entries 2−5). In particular, the commercially available tartaric acid based phosphine (−)-DIOP (P6) gave an encouraging result (73% yield, 98:2 dr and 59% ee) (the absolute configuraton of the 10124

DOI: 10.1021/acs.joc.7b01582 J. Org. Chem. 2017, 82, 10121−10128

Article

The Journal of Organic Chemistry Scheme 4. Proposed Reaction Mechanism

3-Benzyl 2-Ethyl 5-Benzyl-5′-bromo-1′-methyl-2′-oxospiro[cyclopentane-1,3′-indoline]-3-ene-2,3-dicarboxylate (3e). Yellow oil (50.5 mg, 88% yield). 1H NMR (400 MHz, CDCl3): δ 7.36 (ddd, J = 15.1, 9.1, 6.6 Hz, 7H), 7.10−7.02 (m, 3H), 6.84 (t, J = 2.1 Hz, 1H), 6.65−6.57 (m, 2H), 6.41 (d, J = 8.1 Hz, 1H), 5.27 (d, J = 12.4 Hz, 1H), 5.18 (d, J = 12.3 Hz, 1H), 4.42 (t, J = 2.8 Hz, 1H), 3.92−3.81 (m, 1H), 3.59 (q, J = 7.1 Hz, 2H), 2.93 (dd, J = 14.1, 6.3 Hz, 1H), 2.74 (s, 3H), 2.38 (dd, J = 14.1, 11.2 Hz, 1H), 0.71 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 176.5, 167.3, 162.8, 144.5, 142.5, 135.7, 134.7, 132.0, 130.8, 127.7, 127.6, 127.5, 127.3, 127.2, 127.0, 125.3, 113.1, 108.3, 65.5, 59.6, 58.5, 57.9, 52.8, 34.4, 25.1, 12.5. HRMS (ESI-TOF): m/z calcd for C31H29BrNO5 [M + H]+ 574.1224, found 574.1217. 3-Benzyl 2-Ethyl 5-Benzyl-6′-methoxy-1′-methyl-2′-oxospiro[cyclopent[3]ene-1,3′-indoline]-2,3-dicarboxylate (3f). Yellow oil (51.9 mg, 99% yield). 1H NMR (400 MHz, CDCl3): δ 7.34 (t, J = 5.8 Hz, 5H), 7.16 (d, J = 8.2 Hz, 1H), 7.07 (d, J = 6.1 Hz, 3H), 6.81 (s, 1H), 6.64 (d, J = 7.0 Hz, 2H), 6.50 (d, J = 8.1 Hz, 1H), 6.15 (s, 1H), 5.21 (dd, J = 28.7, 12.4 Hz, 2H), 4.40 (s, 1H), 3.82 (s, 4H), 3.57 (q, J = 7.1 Hz, 2H), 2.84 (dd, J = 13.9, 6.6 Hz, 1H), 2.77 (s, 3H), 2.35 (dd, J = 13.7, 10.9 Hz, 1H), 0.68 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 177.6, 167.7, 163.0, 159.9, 144.8, 144.7, 136.3, 134.8, 131.9, 127.7, 127.5, 127.2, 126.9, 125.3, 125.2, 117.1, 104.3, 94.9, 65.4, 59.3, 58.2, 57.9, 54.6, 53.1, 34.5, 25.0, 12.6. HRMS (ESI-TOF): m/z calcd for C32H32NO6 [M + H]+ 526.2224, found 526.2227. 2-tert-Butyl 3-Ethyl 5-Benzyl-6′-methoxy-1′-methyl-2′-oxospiro[cyclopentane-1,3′-indoline]-3-ene-2,3-dicarboxylate (3g). Yellow oil (47.6 mg, 97% yield). 1H NMR (400 MHz, CDCl3): δ 7.18 (d, J = 8.2 Hz, 1H), 7.07 (t, J = 6.0 Hz, 3H), 6.71 (t, J = 2.2 Hz, 1H), 6.65 (dd, J = 7.4, 1.8 Hz, 2H), 6.51 (dd, J = 8.3, 2.3 Hz, 1H), 6.17 (d, J = 2.3 Hz, 1H), 4.33 (dt, J = 10.7, 5.4 Hz, 1H), 4.30−4.11 (m, 2H), 3.84−3.80 (m, 3H), 3.80−3.71 (m, 1H), 2.83 (dd, J = 14.0, 6.6 Hz, 1H), 2.76 (s, 3H), 2.34 (dd, J = 13.9, 10.6 Hz, 1H), 1.27 (t, J = 7.1 Hz, 3H), 0.94 (s, 9H). 13C NMR (101 MHz, CDCl3): δ 177.9, 166.7, 163.7, 160.0, 145.0, 143.5, 136.5, 132.9, 127.8, 127.0, 125.5, 125.2, 117.7, 104.3, 95.1, 79.6, 59.6, 58.7, 58.4, 54.7, 53.1, 34.5, 26.3, 25.0, 13.2. HRMS (ESI-TOF): m/z calcd for C29H34NO6 [M + H]+ 492.2381, found 492.2373. 3-Benzyl 2-tert-Butyl 5-Benzyl-6′-methoxy-1′-methyl-2′oxospiro[cyclopent[3]ene-1,3′-indoline]-2,3-dicarboxylate (3h). Yellow oil (49.7 mg, 90% yield). 1H NMR (400 MHz, CDCl3): δ 7.37− 7.28 (m, 5H), 7.18 (d, J = 8.2 Hz, 1H), 7.07 (d, J = 7.0 Hz, 3H), 6.77 (t, J = 2.2 Hz, 1H), 6.63 (dd, J = 7.3, 1.8 Hz, 2H), 6.52 (s, 1H), 6.17 (d, J = 2.3 Hz, 1H), 5.20 (dd, J = 54.2, 12.4 Hz, 2H), 4.40−4.27 (m, 1H), 3.81 (d, J = 9.7 Hz, 4H), 2.83 (dd, J = 14.0, 6.5 Hz, 1H), 2.74 (d, J = 6.3 Hz, 3H), 2.33 (dd, J = 13.9, 10.8 Hz, 1H), 0.88 (s, 9H). 13C NMR (101 MHz, CDCl3): δ 177.7, 166.6, 163.4, 159.9, 144.9, 144.2,

(d, J = 2.9 Hz, 1H), 7.24 (s, 1H), 7.06 (dd, J = 4.9, 1.6 Hz, 3H), 7.01 (t, J = 7.5 Hz, 1H), 6.77 (t, J = 2.2 Hz, 1H), 6.66−6.54 (m, 3H), 4.48− 4.38 (m, 1H), 4.27−4.19 (m, 2H), 3.85 (ddd, J = 10.3, 6.4, 2.4 Hz, 1H), 3.57 (q, J = 7.1 Hz, 2H), 2.86 (dd, J = 14.0, 6.7 Hz, 1H), 2.80 (s, 3H), 2.36 (dd, J = 14.0, 10.7 Hz, 1H), 1.28 (t, J = 7.1 Hz, 3H), 0.66 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 177.1, 167.7, 163.2, 143.9, 143.4, 136.2, 132.4, 127.9, 127.7, 126.9, 125.2, 125.1, 124.6, 120.7, 106.9, 59.7, 59.3, 58.5, 57.9, 52.9, 34.5, 25.0, 13.2, 12.5. HRMS (ESI-TOF): m/z calcd for C26H28NO5 [M + H]+ 434.1962, found 434.1956. The enantiomeric excess was determined by HPLC (Chiralpak AD-H column: n-hexane/i-PrOH, 90:10 v/v, flow rate = 1.0 mL/min, λ = 254 nm): tR (major) = 52.82 min, tR (minor) = 61.19 min. 3-Ethyl 2-Methyl 5-Benzyl-5′-bromo-1′-methyl-2′-oxospiro[cyclopentane-1,3′-indoline]-3-ene-2,3-dicarboxylate (3b). Yellow oil (43.2 mg, 87% yield). 1H NMR (400 MHz, CDCl3): δ 7.40 (dd, J = 6.9, 1.9 Hz, 2H), 7.07 (dd, J = 4.9, 1.8 Hz, 3H), 6.80 (t, J = 2.2 Hz, 1H), 6.64 (dd, J = 6.5, 2.7 Hz, 2H), 6.44 (d, J = 8.9 Hz, 1H), 4.46− 4.36 (m, 1H), 4.31−4.19 (m, 2H), 3.92−3.82 (m, 1H), 3.19 (s, 3H), 2.93 (dd, J = 14.1, 6.5 Hz, 1H), 2.76 (s, 3H), 2.39 (dd, J = 14.1, 11.0 Hz, 1H), 1.29 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 174.1, 168.4, 162.3, 147.2, 141.5, 135.8, 131.8, 130.7, 127.8, 127.7, 126.9, 125.4, 124.9, 113.8, 108.8, 59.9, 58.6, 58.3, 53.2, 51.4, 33.9, 25.0, 13.1. HRMS (ESI-TOF): m/z calcd for C25H25BrNO5 [M + H]+ 498.0911, found 498.0906. 2-tert-Butyl 3-Ethyl 5′-Chloro-1′,5-dimethyl-2′-oxospiro[cyclopentane-1,3′-indoline]-3-ene-2,3-dicarboxylate (3c). Yellow oil (31.9 mg, 76% yield). 1H NMR (400 MHz, CDCl3): δ 7.29− 7.26 (m, 1H), 7.16 (d, J = 2.0 Hz, 1H), 6.96−6.89 (m, 1H), 6.77 (d, J = 8.3 Hz, 1H), 4.29−4.17 (m, 2H), 3.79 (s, 1H), 3.71−3.60 (m, 1H), 3.22 (s, 3H), 1.42 (s, 9H), 1.30 (t, J = 7.2 Hz, 3H), 0.82 (d, J = 7.5 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 174.7, 166.8, 162.7, 148.0, 146.3, 140.7, 132.1, 127.5, 126.7, 122.7, 108.0, 80.6, 59.7, 59.4, 59.3, 47.1, 26.9, 25.4, 13.2, 12.7. HRMS (ESI-TOF): m/z calcd for C22H27ClNO5 [M + H]+ 420.1572, found 420.1571. Diethyl 5-Benzyl-1′,5′-dimethyl-2′-oxospiro[cyclopentane-1,3′indoline]-3-ene-2,3-dicarboxylate (3d). Yellow oil (40.7 mg, 91% yield). 1H NMR (400 MHz, CDCl3): δ 7.07 (dt, J = 6.4, 5.9 Hz, 5H), 6.77 (t, J = 2.2 Hz, 1H), 6.63 (dd, J = 7.0, 2.3 Hz, 2H), 6.47 (d, J = 7.9 Hz, 1H), 4.48−4.38 (m, 1H), 4.31−4.17 (m, 2H), 3.88−3.73 (m, 1H), 3.58 (q, J = 7.1 Hz, 2H), 2.89−2.81 (m, 1H), 2.80 (s, 3H), 2.39−2.35 (m, 1H), 2.33 (d, J = 6.5 Hz, 3H), 1.28 (t, J = 7.1 Hz, 3H), 0.67 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 177.1, 167.7, 163.4, 144.1, 141.1, 136.4, 132.4, 130.2, 128.2, 127.8, 127.0, 125.4, 125.3, 125.2, 106.7, 59.7, 59.3, 58.7, 57.9, 53.1, 34.5, 25.1, 20.2, 13.2, 12.5. HRMS (ESI-TOF): m/z calcd for C27H30NO5 [M + H]+ 448.2118, found 448.2116. 10125

DOI: 10.1021/acs.joc.7b01582 J. Org. Chem. 2017, 82, 10121−10128

Article

The Journal of Organic Chemistry

141.2, 136.1, 132.0, 131.5, 127.8, 126.7, 125.6, 125.1, 122.4, 120.6, 118.4, 59.2, 58.0, 57.8, 53.2, 50.8, 34.3, 28.4, 17.9, 12.4. HRMS (ESITOF): m/z calcd for C26H28NO5 [M + H]+ 434.1962, found 434.1961. Diethyl 1′,5,5′-Trimethyl-2′-oxospiro[cyclopent[3]ene-1,3′-indoline]-2,3-dicarboxylate (3o). Yellow oil (30.4 mg, 82% yield). 1H NMR (400 MHz, CDCl3): δ 7.06 (d, J = 7.9 Hz, 1H), 6.99 (s, 1H), 6.74 (t, J = 2.2 Hz, 1H), 6.71 (d, J = 7.9 Hz, 1H), 4.42 (t, J = 2.7 Hz, 1H), 4.29−4.20 (m, 2H), 3.64 (q, J = 7.1 Hz, 2H), 3.51−3.40 (m, 1H), 3.24 (s, 3H), 2.28 (s, 3H), 1.29 (t, J = 7.1 Hz, 3H), 0.80 (d, J = 7.4 Hz, 3H), 0.72 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 177.4, 168.0, 163.4, 146.1, 140.5, 131.9, 130.4, 128.0, 125.6, 125.5, 106.6, 59.6, 59.4, 59.3, 57.5, 46.8, 25.6, 20.0, 13.4, 13.2, 12.5. HRMS (ESI-TOF): m/z calcd for C21H26NO5 [M + H]+ 372.1805, found 372.1802. Diethyl 1′,5-Dimethyl-5′-nitro-2′-oxospiro[cyclopentane-1,3′-indolin]-3-ene-2,3-dicarboxylate (3p). Yellow oil (27.7 mg, 69% yield). 1H NMR (400 MHz, CDCl3): δ 7.22−7.15 (m, 1H), 6.97 (t, J = 7.5 Hz, 1H), 6.88−6.79 (m, 1H), 6.73 (t, J = 2.2 Hz, 1H), 4.40 (dd, J = 26.9, 24.2 Hz, 1H), 4.23 (ddt, J = 10.7, 6.9, 3.5 Hz, 2H), 3.63 (q, J = 7.1 Hz, 2H), 3.47 (ddd, J = 9.8, 7.4, 4.9 Hz, 1H), 3.25 (d, J = 16.7 Hz, 3H), 1.29 (t, J = 7.1 Hz, 3H), 0.80 (d, J = 7.3 Hz, 3H), 0.73 (dd, J = 19.4, 12.2 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 177.4, 168.2, 163.0, 145.9, 142.8, 131.8, 127.7, 126.7, 124.6, 120.9, 106.8, 59.6, 59.3, 59.2, 57.7, 46.8, 25.6, 13.4, 13.2, 12.6. HRMS (ESI-TOF): m/z calcd for C20H23N2O7 [M + H]+ 403.1500, found 403.1506. Diethyl 5-Benzyl-5′-chloro-1′-methyl-2′-oxospiro[cyclopent[3]ene-1,3′-indoline]-2,3-dicarboxylate (3q). Yellow oil (35.5 mg, 76% yield). 1H NMR (400 MHz, CDCl3): δ 7.37−7.26 (m, 2H), 7.07 (t, J = 5.7 Hz, 3H), 6.78 (s, 1H), 6.64 (d, J = 7.1 Hz, 2H), 6.51 (dd, J = 31.8, 8.3 Hz, 1H), 4.47−4.27 (m, 1H), 4.23 (ddd, J = 10.5, 6.9, 3.4 Hz, 2H), 4.10−3.86 (m, 1H), 3.85−3.36 (m, 2H), 2.91 (dt, J = 14.3, 7.3 Hz, 1H), 2.77 (s, 3H), 2.37 (ddd, J = 14.0, 11.0, 6.0 Hz, 1H), 1.32− 1.26 (m, 3H), 0.76 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 176.6, 174.2, 167.9, 167.4, 163.1, 162.4, 147.1, 143.7, 142.0, 141.0, 135.8, 135.7, 132.3, 131.8, 131.5, 127.8, 127.7, 127.0, 127.7, 127.0, 126.9, 126.8, 126.6, 126.0, 125.4, 125.3, 124.8, 122.3, 108.3, 107.8, 60.3, 59.9, 59.8, 59.5, 58.6, 58.5, 58.3, 57.9, 53.1, 52.8, 34.4, 33.9, 25.1, 24.9, 13.2, 13.1, 13.0, 12.5. HRMS (ESI-TOF): m/z calcd for C26H27ClNO5 [M + H]+ 468.1572, found 468.1573. 3-Benzyl 2-Ethyl 5-Benzyl-1′-methyl-2′-oxospiro[cyclopent[3]ene-1,3′-indoline]-2,3-dicarboxylate (3r). Yellow oil (42.1 mg, 85% yield). 1H NMR (400 MHz, CDCl3): δ 7.42−7.27 (m, 6H), 7.24 (s, 1H), 7.09−6.97 (m, 4H), 6.83 (t, J = 2.1 Hz, 1H), 6.70−6.46 (m, 3H), 5.22 (dd, J = 28.8, 12.4 Hz, 2H), 4.44 (t, J = 2.8 Hz, 1H), 3.86 (dd, J = 10.9, 5.6 Hz, 1H), 3.65−3.44 (m, 2H), 2.86 (dd, J = 14.0, 6.5 Hz, 1H), 2.79 (s, 3H), 2.36 (dd, J = 14.0, 10.9 Hz, 1H), 0.61 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, CDCl3): δ 177.1, 167.6, 163.0, 144.8, 143.4, 136.1, 134.8, 132.0, 128.0, 127.8, 127.7, 127.5, 127.2, 126.9, 125.2, 125.1, 124.6, 120.7, 106.9, 65.5, 59.3, 58.5, 57.9, 53.0, 34.4, 25.0, 12.4. HRMS (ESI-TOF): m/z calcd for C31H30NO5 [M + H]+ 496.2118, found 496.2115. 2-tert-Butyl 3-Ethyl 1′,5-Dibenzyl-2′-oxospiro[cyclopent[3]ene1,3′-indoline]-2,3-dicarboxylate (3s). Yellow oil (47.8 mg, 89% yield). 1H NMR (400 MHz, CDCl3): δ 7.36−7.28 (m, 3H), 7.26− 6.90 (m, 8H), 6.73 (dd, J = 8.5, 5.2 Hz, 3H), 6.56 (d, J = 7.8 Hz, 1H), 4.71 (d, J = 15.6 Hz, 1H), 4.45 (d, J = 2.4 Hz, 1H), 4.30−4.24 (m, 1H), 4.18 (ddd, J = 26.7, 17.9, 10.6 Hz, 2H), 3.85 (t, J = 8.3 Hz, 1H), 2.74 (dd, J = 13.9, 7.6 Hz, 1H), 2.32 (dd, J = 13.9, 9.4 Hz, 1H), 1.27 (t, J = 7.1 Hz, 3H), 0.86 (s, 9H). 13C NMR (101 MHz, CDCl3): δ 177.7, 166.9, 163.4, 143.2, 142.6, 136.7, 134.8, 133.0, 127.7, 127.6, 127.1, 127.0, 126.6, 126.5, 125.9, 125.5, 125.3, 120.8, 107.9, 79.9, 59.6, 58.6, 58.5, 53.8, 43.2, 34.5, 26.2, 13.2. HRMS (ESI-TOF): m/z calcd for C34H3 6NO5 [M + H]+ 538.2588, found 538.2588. 3-Benzyl 2-tert-Butyl 1′,5-Dibenzyl-2′-oxospiro[cyclopent[3]ene1,3′-indoline]-2,3-dicarboxylate (3t). Yellow oil (50.9 mg, 85% yield). 1 H NMR (400 MHz, CDCl3): δ 7.40−7.26 (m, 9H), 7.25−7.14 (m, 3H), 7.14−7.08 (m, 3H), 6.98 (t, J = 7.5 Hz, 1H), 6.79 (t, J = 2.1 Hz, 1H), 6.70 (dd, J = 6.4, 2.7 Hz, 2H), 6.56 (d, J = 7.8 Hz, 1H), 5.20 (dd, J = 31.2, 12.4 Hz, 2H), 4.69 (d, J = 15.6 Hz, 1H), 4.46 (t, J = 2.8 Hz,

136.3, 134.7, 132.4, 127.7, 127.4, 127.2, 127.1, 126.9, 125.4, 125.1, 117.6, 104.2, 95.0, 79.6, 65.5, 58.5, 58.3, 54.7, 53.0, 34.3, 26.2, 24.9. HRMS (ESI-TOF): m/z calcd for C34H36NO6 [M + H]+ 554.2537, found 554.2527. 3-Ethyl 2-Methyl 6′-Methoxy-1′-methyl-2′-oxospiro[cyclopentane-1,3′-indoline]-3-ene-2,3-dicarboxylate (3i). Yellow oil (32.7 mg, 91% yield). 1H NMR (400 MHz, CDCl3): δ 7.07 (d, J = 8.3 Hz, 1H), 6.97 (d, J = 2.1 Hz, 1H), 6.49 (dd, J = 8.3, 2.1 Hz, 1H), 6.41 (d, J = 2.0 Hz, 1H), 4.27 (d, J = 2.0 Hz, 1H), 4.21 (ddd, J = 10.8, 9.0, 3.7 Hz, 2H), 3.81 (s, 3H), 3.27 (s, 3H), 3.23 (s, 3H), 3.10 (dd, J = 18.5, 2.0 Hz, 1H), 2.78 (dd, J = 18.5, 2.1 Hz, 1H), 1.28 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 179.1, 169.5, 163.0, 159.9, 144.0, 142.3, 133.3, 123.8, 121.9, 105.5, 95.4, 59.9, 58.2, 54.8, 53.5, 50.9, 43.5, 25.9, 13.5. HRMS (ESI-TOF): m/z calcd for C19H22NO6 [M + H]+ 360.1442, found 360.1439. 2-Ethyl 3-Methyl 5-Benzyl-6′-methoxy-1′-methyl-2′-oxospiro[cyclopent[3]ene-1,3′-indoline]-2,3-dicarboxylate (3j). Yellow oil (42.6 mg, 95% yield). 1H NMR (400 MHz, CDCl3): δ 7.15 (d, J = 8.2 Hz, 1H), 7.08 (t, J = 6.0 Hz, 3H), 6.77 (t, J = 2.2 Hz, 1H), 6.69− 6.62 (m, 2H), 6.51 (dd, J = 8.3, 2.3 Hz, 1H), 6.16 (d, J = 2.3 Hz, 1H), 4.39 (t, J = 2.8 Hz, 1H), 3.82 (s, 3H), 3.81−3.78 (m, 1H), 3.77 (s, 3H), 3.61 (qd, J = 7.1, 2.0 Hz, 2H), 2.84 (dd, J = 13.9, 6.7 Hz, 1H), 2.78 (s, 3H), 2.35 (dd, J = 13.9, 10.5 Hz, 1H), 0.72 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, CDCl3): δ 177.6, 167.7, 163.7, 159.8, 144.7, 144.4, 136.3, 131.9, 127.7, 126.9, 125.2, 117.1, 104.3, 94.9, 59.3, 58.2, 57.8, 54.6, 53.1, 50.8, 34.5, 25.1, 12.6. HRMS (ESI-TOF): m/z calcd for C26H28NO6 [M + H]+ 450.1911, found 450.1910. Dimethyl 5-Benzyl-6′-methoxy-1′-methyl-2′-oxospiro[cyclopent[3]ene-1,3′-indoline]-2,3-dicarboxylate (3k). Yellow oil (36.1 mg, 83% yield). 1H NMR (400 MHz, CDCl3): δ 7.14 (d, J = 8.2 Hz, 1H), 7.09 (q, J = 5.1 Hz, 3H), 6.79 (t, J = 2.1 Hz, 1H), 6.70−6.62 (m, 2H), 6.51 (dd, J = 8.3, 2.3 Hz, 1H), 6.18 (d, J = 2.2 Hz, 1H), 4.40 (t, J = 2.7 Hz, 1H), 3.83 (s, 3H), 3.80 (d, J = 2.1 Hz, 1H), 3.77 (s, 3H), 3.14 (s, 3H), 2.85 (dd, J = 14.0, 7.0 Hz, 1H), 2.79 (s, 3H), 2.36 (dd, J = 13.8, 10.4 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ 177.6, 168.3, 163.6, 159.8, 144.7, 144.6, 136.3, 131.7, 127.7, 126.9, 125.2, 125.1, 117.1, 104.3, 94.9, 58.1, 57.9, 54.5, 53.1, 50.8, 50.4, 34.5, 25.1. HRMS (ESITOF): m/z calcd for C25H26NO6 [M + H]+ 436.1755, found 436.1754. Diethyl 6′-Methoxy-1′,5-dimethyl-2′-oxospiro[cyclopentane-1,3′indolin]-3-ene-2,3-dicarboxylate (3l). Yellow oil (36.8 mg, 95% yield). 1H NMR (400 MHz, CDCl3): δ 7.07 (d, J = 8.2 Hz, 1H), 6.72 (t, J = 2.0 Hz, 1H), 6.46 (dd, J = 8.3, 2.2 Hz, 1H), 6.40 (d, J = 2.2 Hz, 1H), 4.38 (t, J = 2.5 Hz, 1H), 4.22 (dd, J = 14.0, 7.0 Hz, 2H), 3.80 (s, 3H), 3.68 (q, J = 7.1 Hz, 2H), 3.43 (qd, J = 7.3, 4.9 Hz, 1H), 3.24 (s, 3H), 1.28 (t, J = 7.1 Hz, 3H), 0.95−0.76 (m, 6H). 13C NMR (101 MHz, CDCl3): δ 178.1, 168.1, 163.3, 159.6, 146.1, 144.2, 131.9, 125.5, 117.4, 104.4, 95.0, 59.6, 59.3, 59.0, 57.6, 54.5, 46.9, 25.6, 13.4, 13.2, 12.7. HRMS (ESI-TOF): m/z calcd for C21H26NO6 [M + H]+ 388.1755, found 388.1749. 3-Benzyl 2-Methyl 5-Benzyl-1′,7′-dimethyl-2′-oxospiro[cyclopent[3]ene-1,3′-indoline]-2,3-dicarboxylate (3m). Yellow oil (47.5 mg, 96% yield). 1H NMR (400 MHz, CDCl3): δ 7.44−7.27 (m, 5H), 7.08 (dd, J = 6.9, 3.8 Hz, 4H), 6.88 (ddd, J = 18.1, 13.8, 4.8 Hz, 3H), 6.69−6.42 (m, 2H), 5.22 (dd, J = 44.1, 12.4 Hz, 2H), 4.54−3.97 (m, 1H), 3.85 (ddt, J = 8.3, 6.0, 3.1 Hz, 1H), 3.06 (s, 3H), 3.02 (s, 3H), 2.88 (dd, J = 14.0, 6.3 Hz, 1H), 2.45−2.30 (m, 4H). 13C NMR (101 MHz, CDCl3): δ 177.9, 168.2, 163.0, 145.1, 141.0, 136.0, 134.7, 131.8, 131.6, 127.7, 127.5, 127.2, 126.9, 126.7, 125.5, 125.1, 122.3, 120.5, 118.5, 65.4, 58.1, 57.7, 53.3, 50.3, 34.3, 28.5, 18.0. HRMS (ESITOF): m/z calcd for C31H30NO5 [M + H]+ 496.2118, found 496.2123. 2-Ethyl 3-Methyl 5-Benzyl-1′,7′-dimethyl-2′-oxospiro[cyclopent[3]ene-1,3′-indoline]-2,3-dicarboxylate (3n). Yellow oil (37.7 mg, 87% yield). 1H NMR (400 MHz, CDCl3): δ 7.16−7.02 (m, 4H), 6.97 (d, J = 7.6 Hz, 1H), 6.88 (t, J = 7.5 Hz, 1H), 6.76 (s, 1H), 6.69−6.45 (m, 2H), 4.43 (t, J = 2.7 Hz, 1H), 3.89−3.80 (m, 1H), 3.77 (d, J = 4.2 Hz, 3H), 3.72−3.43 (m, 2H), 3.00 (d, J = 24.9 Hz, 3H), 2.87 (dd, J = 13.9, 6.4 Hz, 1H), 2.46−2.27 (m, 4H), 0.66 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 178.0, 167.6, 163.8, 144.3, 10126

DOI: 10.1021/acs.joc.7b01582 J. Org. Chem. 2017, 82, 10121−10128

Article

The Journal of Organic Chemistry 1H), 4.23 (d, J = 15.6 Hz, 1H), 3.85 (dd, J = 11.2, 5.4 Hz, 1H), 2.73 (dd, J = 14.0, 7.6 Hz, 1H), 2.32 (dd, J = 14.0, 9.4 Hz, 1H), 0.79 (s, 9H). 13C NMR (101 MHz, CDCl3): δ 177.6, 166.8, 163.3, 144.0, 142.7, 136.6, 134.8, 134.7, 132.7, 127.8, 127.7, 127.5, 127.3, 127.1, 127.1, 126.6, 126.5, 125.6, 125.3, 125.2, 120.8, 107.9, 80.0, 65.5, 58.7, 58.5, 53.8, 43.3, 34.5, 26.2. HRMS (ESI-TOF): m/z calcd for C39H38NO5 [M + H]+ 600.2744, found 600.2738. Diethyl 1′-Methyl-2′-oxospiro[cyclopent[3]ene-1,3′-indoline]-2,3dicarboxylate (3u). Yellow oil (29.5 mg, 86% yield). 1H NMR (400 MHz, CDCl3): δ 7.28 (dd, J = 7.8, 1.1 Hz, 1H), 7.19 (d, J = 6.9 Hz, 1H), 6.99 (td, J = 7.6, 0.8 Hz, 1H), 6.95 (dd, J = 4.7, 2.4 Hz, 1H), 6.82 (d, J = 7.8 Hz, 1H), 4.34 (dd, J = 4.4, 2.2 Hz, 1H), 4.28−4.15 (m, 2H), 3.74−3.58 (m, 2H), 3.26 (s, 3H), 3.13 (dt, J = 18.4, 2.4 Hz, 1H), 2.78 (dt, J = 18.4, 2.4 Hz, 1H), 1.28 (t, J = 7.1 Hz, 3H), 0.75 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 178.1, 168.3, 162.7, 142.3, 141.4, 133.2, 130.0, 127.8, 122.8, 121.7, 106.8, 59.6, 59.4, 58.0, 53.7, 43.1, 25.6, 13.2, 12.6. HRMS (ESI-TOF): m/z calcd for C19H22NO5 [M + H]+ 344.1492, found 344.1494. Diethyl 5-Benzyl-1′-methyl-2′-oxospiro[cyclopent[3]ene-1,3′-indoline]-2,3-dicarboxylate (3a′). Yellow oil (37.3 mg, 86% yield). 1 H NMR (400 MHz, CDCl3): δ 7.29 (d, J = 2.7 Hz, 1H), 7.26 (d, J = 8.8 Hz, 1H), 7.08−7.05 (m, 3H), 7.01 (t, J = 7.5 Hz, 1H), 6.78 (t, J = 2.0 Hz, 1H), 6.60 (dt, J = 16.1, 7.2 Hz, 3H), 4.43 (t, J = 2.7 Hz, 1H), 4.28−4.19 (m, 2H), 3.89−3.81 (m, 1H), 3.57 (q, J = 7.1 Hz, 2H), 2.86 (dd, J = 14.0, 6.6 Hz, 1H), 2.80 (s, 3H), 2.36 (dd, J = 13.9, 10.7 Hz, 1H), 1.28 (t, J = 7.1 Hz, 3H), 0.65 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 177.1, 167.7, 163.3, 143.9, 143.4, 136.2, 132.4, 127.9, 127.7, 126.9, 125.2, 125.1, 124.6, 120.7, 106.9, 59.7, 59.3, 58.5, 57.9, 52.9, 34.5, 25.0, 13.2, 12.5.

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S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b01582. 1 H and 13C NMR spectra for all products (PDF) X-ray data for compound 3a (CIF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Zhiwei Miao: 0000-0002-8488-8670 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the National Key Research and Development Program of China (2016YFD0201200), the Committee of Science and Technology of Tianjin (15JCYBJC20700) and State Key Laboratory of Elemento-Organic Chemistry in Nankai University for financial support. We also thank the anonymous reviewer for helpful suggestions to improve our manuscript.

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REFERENCES

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DOI: 10.1021/acs.joc.7b01582 J. Org. Chem. 2017, 82, 10121−10128

Article

The Journal of Organic Chemistry (15) Crystallographic data for the structural analysis of compound 3a have been deposited at the Cambridge Crystallographic Data Centre as No. CCDC 1540158. These data can be obtained free of charge by contacting the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: + 44 1223 336033; E-mail: [email protected]. (16) (a) Zhang, C. M.; Lu, X. Y. J. Org. Chem. 1995, 60, 2906. (b) Sampath, M.; Loh, T. P. Chem. Sci. 2010, 1, 739. (c) Pham, T. Q.; Pyne, S. G.; Skelton, B. W.; White, A. H. J. Org. Chem. 2005, 70, 6369.

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DOI: 10.1021/acs.joc.7b01582 J. Org. Chem. 2017, 82, 10121−10128