Bifunctional Quaternary Ammonium Salts Catalyzed Stereoselective

Apr 14, 2017 - Bifunctional Quaternary Ammonium Salts Catalyzed Stereoselective Conjugate Addition of Oxindoles to Electron-Deficient β-Haloalkenes. ...
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Bifunctional Quaternary Ammonium Salts Catalyzed Stereoselective Conjugate Addition of Oxindoles to Electron-Deficient β‑Haloalkenes Qiaowen Jin,† Changwu Zheng,‡ Gang Zhao,*,‡ and Gang Zou*,† †

School of Chemistry & Molecular Engineering, East China University of Science & Technology, 130 Meilong Road, Shanghai 200237, China ‡ Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China S Supporting Information *

ABSTRACT: A highly Z-selective asymmetric conjugate addition of 3-substituted oxindoles to β-haloalkene ketones/esters catalyzed by readily available chiral bifunctional quaternary ammonium salts is reported. This reaction provides efficient access to a range of 2oxoindole derivatives bearing a thermodynamically unstable Zolefin structure and a chiral quaternary carbon center in high yields (up to 90%) and with good to high stereoselectivities (up to >19:1 Z/E and 91% ee) under mild conditions.

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INTRODUCTION

Enantioenriched quaternary carbon centers are of great interest to chemists on account of their occurrence in numerous natural products, and their construction remains a significant challenge in organic synthetic chemistry.1 Among the efforts to address this challenge, the Michael addition of prochiral nucleophiles to α,β-unsaturated carbonyl compounds has been widely used with great progress being achieved.2 These reactions are usually featured with a newly formed Csp3−Csp3 bond. On the other hand, examples in the construction of chiral quaternary carbon centers with this strategy via the formation of a Csp2−Csp3 bond are limited, which probably due to the challenges to control both the E/Z selectivity and enantioselectivity.3 In this regard, electron-deficient alkynes are the mostly used electrophiles with a series of nucleophiles such as oxazolones, pyrazolones and cyanoacetates.4 Particularly, Wu5 and Feng6 have reported the asymmetric addition of C3-substituted oxindoles to propiolates by using chiral cinchona-derived tertiary amine-urea catalysts and N,N′-dioxide metal complexes, respectively (Scheme 1). β-Haloalkenes, an alternative electrophile has also been developed by Jørgensen in the reaction with β-ketoesters to construct quaternary centers.7 As part of our ongoing project on the development of chiral amino acidderived bifunctional chiral quaternary ammonium and phosphonium salts as phase-transfer catalysts in asymmetric addition reactions to construct quaternary centers,8 we report herein the stereoselective conjugate addition of C3-substituted oxindoles to electron-deficient β-haloalkenes to construct vinylic substituted oxindoles bearing quaternary carbon centers in high yields and enantioselectivity and excellent Z/E selectivity by asymmetric phase-transfer catalysis using bifunctional quaternary ammonium salts as catalysts. © 2017 American Chemical Society

RESULTS AND DISCUSSION

The initial investigation focused on the evaluation of chiral catalysts in the conjugate addition between 3-phenyloxindole (1a) and (Z)-β-chloro-1-phenyl propenone ((Z)-2a). The reaction with bifunctional quaternary phosphonium salts catalysts gave the product 4a in low enantioselectivity and moderate Z/E selectivity (Table 1, entries 1−2), which were improved when L-isoleucine-derived quaternary ammonium iodide salt 3c was used. Then, a series of amino acids-derived quaternary ammonium salts with different chiral skeletons, amide moieties and ammonium centers were investigated subsequently (entries 4−9). Catalyst 3i with a 3,5-bistrifluoromethyl amide subunit and a 2,4-bistrifluoromethylbenzyl ammonium center turned out to be the optimal catalyst, giving the product in 88% yield, 81% ee and >19:1 Z/E ratio (entry 9). The screening of several different bases revealed that the use of relatively stronger bases led to decreases in both enantioselectivity and Z selectivity while a relatively weaker base KF increased the enantioselectivity to 88% (entries 10− 13). Considering the possible halogen anion on the effect on this reaction, the catalyst 3j with F− as the counteranion was investigated. As compared to catalyst 3i with Br− as the counteranion, the catalyst 3j catalyzed the reaction with equal efficiency, while an appreciably lower enantioselectivity was obtained (entry 15 vs entry 12). This result suggests the exchange between F− and Br− might be minimal during the reaction course. Further optimization of the reaction conditions indicated toluene is the best solvent and the selectivity did not improve at a lower temperature (entries 16−19). Received: March 10, 2017 Published: April 14, 2017 4840

DOI: 10.1021/acs.joc.7b00571 J. Org. Chem. 2017, 82, 4840−4850

Article

The Journal of Organic Chemistry Scheme 1. Asymmetric Vinylation of 3-Substituted Oxindoles

configuration of 4c was deduced to be S by comparison of the specific optical rotation data of E-5c with literature data and the absolute configurations of other adducts were assigned by analogy (Scheme 3). Furthermore, compound E-5w could be easily reduced to 6w in the presence of Pd/C and hydrogen and the enantioselectivity was retained. Importantly, the optically active Z-selective adduct 4u could be easily transformed into the spirocyclic product 7 through an intramolecular Heck reaction followed by oxidative cleavage without loss of optical purity. To get some insights into the catalytic mechanism, we performed some control experiments to test the role of the Hbonding and the quaternary ammonium center of the bifunctional phase-transfer catalysts. When catalyst 3k, which lacks the quaternary ammonium center as compared to 3i, was used, the enantioselectivity of 4a slumped to 3% ee, and similar results was obtained when 3l with the amide NH (H-bonding donor) being blocked was used (Scheme 4). These results suggested that both the H-bonding interaction and quaternary ammonium center were crucial for the asymmetric induction. With the above results and the X-ray structure of catalyst 3h, we proposed a tentative transition state to explain the enantioselectivity of the reaction. As shown in Scheme 5, we propose that the oxindoles could only be activated by the amide N−H bonding and the ammonium from the bottom face. Such an assembly would only make the following attack to the βchloroalkenes from the bottom and resulted in the products with S-configuration. The substitution of halide with retention of configuration can be explained through an AdN-E mechanism (Scheme 6).7 The

With the optimized conditions in hand, a series of 3substituted oxindoles and β-haloalkenes were examined in the reaction (Scheme 2). The reactions proceeded well for 3substituted oxindoles bearing electron-donating or electronwithdrawing groups on either of the benzene ring (4b−4k). The product (4l) was obtained with a reduced ee, which is probably due to the presence of the bulky t-butyl group in the benzene ring of R1. Different aromatic and heteroaromatic βchloropropenones were also evaluated under this catalytic reaction and the products 4m−4s were obtained in good yields, good to high enantioselectivities and excellent Z-configuration retention. Replacement of the 3-aryl group (R1) with a benzyl, methyl or ethoxycarbonyl group in substrate 1 also proved to be suitable with respect to enantioselectivity and Z/E selectivity (4t−4w). To our delight, the unprecedented use of 3-alkenyl or 3-alkynyl substituted oxindoles as nucleophile in the reaction also performed well to give the desired products (4x−4ab) in excellent enantioselectivity and Z/E selectivity. It should be noted that the product 4ab has the key skeleton of the natural product terpeptin.9 Changing the leaving group in 2 from Cl− to Br− was also applicable, giving the desired product 4a with the same results. In a similar manner, the E product could be obtained using (E)-2a as the substrate, however, the enantioselectivity decreased to 59% (E-4a). Unfortunately, (Z)-2ab, with an ester as the activating group, underwent the transformation to afford the product 5 with a poor yield and enantioselectivity. The adducts 4c and 4w could undergo isomerization to afford the corresponding thermodynamically stable E-5c and E5w in the presence of trifluoroacetic acid (TFA). The absolute 4841

DOI: 10.1021/acs.joc.7b00571 J. Org. Chem. 2017, 82, 4840−4850

Article

The Journal of Organic Chemistry Table 1. Optimization of Reaction Conditionsa

Scheme 2. Substrate Scope

entry

catalyst

solvent

base

t (h)

Y (%)b

ee (%)c

Z/Ed

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

3a 3b 3c 3d 3e 3f 3g 3h 3i 3i 3i 3i 3i 3j 3j 3i 3i 3i 3i

toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene THF DCM o-xylene toluene

K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 KOH Na2CO3 KF CsF K2CO3 KF KF KF KF KF

3.5 4 8 4 4 4 4 4 4 1.5 5 4 3 4 4 >24 6 3 8

80 83 70 82 86 75 88 87 88 80 70 87 85 88 87 64 73 76 72

32 37 60 74 60 67 64 73 81 56 85 88 77 78 81 83 86 78 88

10:1 10:1 17:1 >19:1 >19:1 >19:1 >19:1 >19:1 >19:1 15:1 >19:1 >19:1 18:1 >19:1 >19:1 >19:1 >19:1 >19:1 >19:1

Scheme 3. Synthetic Application of the Adducts 4

a

Unless otherwise noted, the reaction was conducted with 0.1 mmol of 1a, 0.15 mmol of 2a, and 2.0 equiv of base in the presence of 10 mol % of catalyst 3 at r.t. bIsolated yield. cDetermined by chiral HPLC analysis. dDetermined by 1H NMR spectroscopic. eReaction performed at 0 °C.

stereoselective addition results in the formation of a mixture of disatereomeric intermediates, β-halo-substituted enolates 8, which undergo rapid elimination of the leaving group to regenerate the CC double bond. As stereoelectronic effects require the periplanar alignment of the C−X σ* orbital and the enolate π orbital for the elimination, two ways can achieve such conformations through either a small bond rotation (ca. 60°) or a larger rotation (ca. 120°). The preference for the small one, which results in retention of the configuration of the CC double bond, may be rationalized by the avoidance of destabilizing eclipsing interactions during the rotation and hyperconjugation between the σ* orbital of the C−X group and the electron-rich π system of the enolate,10 and the two intermediates 8 in Scheme 6 finally transform to the same product.

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CONCLUSIONS In conclusion, we have developed a highly Z-selective asymmetric conjugate addition between 3-substituted oxindoles and electron-deficient haloalkenes in the presence of readily available chiral quaternary ammonium salt catalyst. This methodology tolerates a series of 3-aryl and 3-alkyl substituted oxindoles under mild conditions, gives oxindoles derivatives bearing a chiral quaternary carboncenter in high yields, enantioselectivity and E/Z selectivity. Efforts toward a deeper understanding of the mechanism and the application of the ammonium salt catalysts to other transformations are currently under investigation. 4842

DOI: 10.1021/acs.joc.7b00571 J. Org. Chem. 2017, 82, 4840−4850

Article

The Journal of Organic Chemistry Scheme 4. Control Experiments

Scheme 6. Proposed AdN-E Mechanism

Scheme 5. X-ray Structure of Catalyst 3h (Thermal Ellipsoids at 50% Probability Level) and Proposed Transition-State Model

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EXPERIMENTAL SECTION

a rotary evaporator and the residue was purified by silica gel chromatography (petrolume ether/ethyl acetate = 12/1−9/1) to afford the product 1u (2.2 g, 25% yield). tert-Butyl 3-(2-bromobenzyl)-2-oxoindoline-1-carboxylate (1u). Yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.19−7.27 (m, 3H), 7.13−7.17 (m, 1H), 6.97 (t, J = 7.6 Hz, 1H), 6.62 (d, J = 7.2 Hz, 1H), 3.99 (dd, J = 7.0 Hz, 9.6 Hz, 1H), 3.58 (dd, J = 5.6 Hz, 13.6 Hz, 1H), 2.97 (dd, J = 9.6 Hz, 14.0 Hz, 1H), 1.64 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 175.2, 149.3, 140.0, 137.2, 133.1, 132.2, 128.7, 128.2, 127.3, 127.1, 124.8, 124.5, 123.9, 114.8, 84.3, 45.1, 38.3, 28.1 IR (KBr) 3062, 2979, 2929, 1793, 1767, 1730, 1607, 1479, 1465, 1442, 1393, 1351, 1299, 1251, 1149, 1093, 1025, 1002, 842, 751, 656, 634, 598, 446. HRMS (ESI-TOF) m/ z [M + H]+ Calcd for C20H21BrNO3 402.0705; found 402.0698. To a stirred mixture of sodium hydride (80 mg, 2.0 mmol) and 3allyl substituted oxindole (402 mg, 2.0 mmol) in THF (20 mL) was added dropwise Boc anhydride (436 mg, 2.0 mmol) at 0 °C. The resulting mixture was stirred for 10 min at 0 °C and then poured into cold water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude material was purified by chromatography by silica gel chromatography (hexane/acetone = 99/1) to give 1ab (240 mg, 40% yield). tert-Butyl 3-(3-methylbut-2-en-1-yl)-2-oxoindoline-1-carboxylate (1ab). Yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.0 Hz, 1H), 7.16−7.22 (m, 2H), 7.03 (t, J = 7.2 Hz, 1H), 5.02−5.06 (m, 1H), 3.45−3.47 (m, 1H), 2.61−2.66 (m, 1H), 2.48−2.55 (m, 1H), 1.59 (s, 3H), 1.56 (s, 9H), 1.48 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 175.8, 149.3, 140.1, 135.2, 128.0, 127.9, 123.9, 119.4, 114.8, 84.1, 46.2, 30.1, 28.1, 25.8, 18.0. IR (KBr) 2978, 2932, 1773, 1731, 1582, 1522,

General Information. Nuclear magnetic resonance spectra were recorded at 400 MHz. All chemical shifts (δ) were given in ppm. Data were reported as follows: chemical shift, intergration, multiplicity (s = single, d = doublet, t = triplet, q = quarter, br = broad, m= multiplet, cm = complex multiplet) and coupling constants (Hz). Flash column chromatography was performed using H silica gel. For thin-layer chromatography (TLC), silica gel plates (HSGF 254) were used and compounds were visualized by irradiation with UV light. Analytical high performance liquid chromatography (HPLC) was carried out using chiral columns. Melting points were uncorrected. Optical rotations were measured at λ = 589 nm. High-resolution mass spectra were recorded using TOF mass analyzer. The synthesis of 3substituted oxindoles,11 (Z)-212 and the catalysts 3a, 3b8b were performed according to reported methods. Procedure for the Preparation of Substrates 1u and 1ab. A mixture of the 2-oxindole (1.3 g, 10 mmol), 2-bromobenzaldehyde (3.7 g, 20 mmol) and piperidine (1.7 g, 20 mmol) in ethanol (80 mL) was stirred at 90 °C for 4 h. After the mixture was cooled, the precipitate was filtered, washed with cold ethanol and the crude product was dissolved in methanol (100 mL). NaBH4 (760 mg, 20 mmol) was added and the reaction mixture was stirred at room temperature for 5 h. The resulting solution was poured into cold water, and the organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure and the crude product was treated with NaH (880 mg, 22 mmol) and di(tert-butyl) carbonate (4.8 g, 22 mmol) in anhydrous THF at 0 °C for 10 min under argon. After completion of the reaction, the resulting solution was poured into satd. aq. NH4Cl, and the organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure using 4843

DOI: 10.1021/acs.joc.7b00571 J. Org. Chem. 2017, 82, 4840−4850

Article

The Journal of Organic Chemistry 1479, 1392, 1368, 1349, 1294, 1251, 751. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C18H24NO3 302.1756; found 302.1750. Typical Procedure for the Preparation of Bifunctional Ammonium Salts 3c−3i. With a modified method according to ref 11: to a stirred solution of Boc-protected α-amino acid (2.0 mmol) in CH2Cl2 (10.0 mL) were added HBTU (3.0 mmol, 1.5 equiv) and DIPEA (4.0 mmol, 2.0 equiv) at 0 °C. Then dimethylamine (2.0 mmol, 1.0 equiv) was added and the reaction mixture was vigorously stirred at room temperature and monitored by TLC. After 2 h, the resulting solution was poured into 100 mL of H2O, and the organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure and the crude product was dissolved into a mixture of TFA (4.0 mmol)/CH2Cl2 (20 mL), and the resulting mixture was stirred at room temperature overnight. The mixture was extracted water first and then the combined aqueous layer was basified with satd. aq. NaHCO3 solution, which was then extracted with CH2Cl2. The combined organic phases were dried over anhydrous Na2SO4, and concentrated under reduced pressure. After that, the crude product was added dropwise into a suspension of LiAlH4 (6.0 mmol, 3.0 equiv) in dried THF (30 mL) at 0 °C. The mixture was stirred at 75 °C for 24 h before being carefully quenched by sequential addition of water until the stop of gas evolution. Then anhydrous Na2SO4 was added into the mixture, and the mixture was filtered through silica gel and the filtrate was concentrated under reduced pressure. The crude product was dissolved into CH2Cl2, and then benzoic acid (2.2 mmol, 1.1 equiv), HBTU (3.0 mmol, 1.5 equiv) and DIPEA (4.0 mmol, 2.0 equiv) were added into this solution and stirred overnight. The resulting solution was poured into aq. NaOH to adjust the pH > 7, and the aqueous layer was extracted with DCM. The combined organic layers were washed with water and brine, and concentrated in vacuo to afford the crude product, which could be used directly in the next step. The crude product was dissolved in a solution of CH3CN (5.0 mL)/RBr (or MeI) (4.0 mmol, 2.0 equiv), and the resulting mixture was stirred at room temperature overnight and monitored by TLC. After completion of the reaction, the solvent was removed under reduced pressure using a rotary evaporator and the residue was purified by silica gel chromatography (CH2Cl2/methanol = 1/20) to afford the desired products 3c−3i. Procedure for the Preparation of Catalyst 3j. To a stirred solution of 3i in methanol was added Amberlyst A-26(OH) (10.0 equiv) and the resulting mixture was stirred overnight. Then the mixture was filtered through silica gel. To the filtrate was added hydrofluoric acid (1.5 equiv), and the resulting solution was stirred at room temperature for 2 h before being poured into water. The aqueous layer was extracted with DCM, and the combined organic layers were washed with water and brine, concentrated under reduced pressure using a rotary evaporator and purified by silica gel chromatography (CH2Cl2/methanol = 1/20) to afford the desired product 3j. Procedure for the Preparation of Catalyst 3k. To a stirred solution of Boc-protected L-isoleucine (2.0 mmol) in CH2Cl2 (10.0 mL) were added HBTU (3.0 mmol, 1.5 equiv) and DIPEA (4.0 mmol, 2.0 equiv) at 0 °C. Then dimethylamine (2.0 mmol, 1.0 equiv) was added and the reaction mixture was vigorously stirred at room temperature and monitored by TLC. After 2 h, the resulting solution was poured into 100 mL of H2O, and the organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure and the crude product was dissolved into a mixture of TFA (4.0 mmol)/CH2Cl2 (20 mL), and the resulting mixture was stirred at room temperature overnight. The mixture was extracted water first and then the combined aqueous layer was basified with satd. aq. NaHCO3 solution, which was then extracted with CH2Cl2. The combined organic phases were dried over anhydrous Na2SO4, and concentrated under reduced pressure. After that, the crude product was added dropwise into a suspension of LiAlH4 (6.0 mmol, 3.0 equiv) in dried THF (30 mL) at 0 °C. The mixture was stirred at 75 °C for 24 h before being carefully quenched by sequential addition of water until the stop of gas evolution. Then anhydrous Na2SO4 was added into the mixture, and the mixture was filtered through silica gel and the filtrate was concentrated under reduced pressure. The crude product was

dissolved into CH2Cl2, and then 3,5-bis(trifluoromethyl)benzoic acid (2.2 mmol, 1.1 equiv), HBTU (3.0 mmol, 1.5 equiv) and DIPEA (4.0 mmol, 2.0 equiv) were added into this solution and stirred overnight. The resulting solution was poured into aq. NaOH to adjust the pH > 7, and the aqueous layer was extracted with DCM. The combined organic layers were washed with water and brine, and concentrated in vacuo to afford the crude product, which could be purified by silica gel chromatography (CH2Cl2/methanol = 1/20) to afford product 3k. Procedure for the Preparation of Catalyst 3l. To a stirred solution of Boc-protected L-isoleucine (2.0 mmol) in CH2Cl2 (10.0 mL) were added HBTU (3.0 mmol, 1.5 equiv) and DIPEA (4.0 mmol, 2.0 equiv) at 0 °C. Then dimethylamine (2.0 mmol, 1.0 equiv) was added and the reaction mixture was vigorously stirred at room temperature and monitored by TLC. After 2 h, the resulting solution was poured into 100 mL of H2O, and the organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure and the crude product was added dropwise into a suspension of LiAlH4 (6.0 mmol, 3.0 equiv) in dried THF (30 mL) at 0 °C. The mixture was stirred at 75 °C for 24 h before being carefully quenched by sequential addition of water until the stop of gas evolution. Then anhydrous Na2SO4 was added into the mixture, and the mixture was filtered through silica gel and the filtrate was concentrated under reduced pressure. The crude product was dissolved into CH2Cl2, and then 3,5-bis(trifluoromethyl)benzoic acid (2.2 mmol, 1.1 equiv), HBTU (3.0 mmol, 1.5 equiv) and DIPEA (4.0 mmol, 2.0 equiv) were added into this solution and stirred overnight. The resulting solution was poured into aq. NaOH to adjust the pH > 7, and the aqueous layer was extracted with DCM. The combined organic layers were washed with water and brine, and concentrated in vacuo to afford the crude product, which could be used directly in the next step. The crude product was dissolved in a solution of CH3CN (5.0 mL)/2,4bis(trifluoromethyl)benzyl bromide (4.0 mmol, 2.0 equiv), and the resulting mixture was stirred at room temperature overnight and monitored by TLC. After completion of the reaction, the solvent was removed under reduced pressure using a rotary evaporator and the residue was purified by silica gel chromatography (CH2Cl2, CH2Cl2/ methanol as the eluent) to afford the desired products 3l. (2S,3S)-2-(3,5-Bis(trifluoromethyl)benzamido)-N,N,N,3-tetramethylpentan-1-aminium iodide (3c). 85 mg, yield 80%, yellow oil. 1H NMR (400 MHz, DMSO-d6) δ 9.24 (d, J = 8.8 Hz, 1H), 8.57 (s, 2H), 8.37 (s, 1H), 4.40 (br, 1H), 3.65−3.76 (m, 2H), 3.13 (s, 9H), 1.71 (br, 1H), 1.48−1.54 (br, 1H), 1.18−1.23 (m, 1H), 0.96 (d, J = 6.8 Hz, 3H), 0.90 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, DMSO-d6) δ 163.7, 136.5, 131.0 (q, J = 33.0 Hz), 128.7, 125.7, 123.6 (q, J = 271.4 Hz), 66.9, 53.3, 49.5, 38.9, 24.9, 15.2, 11.7. 19F NMR (376 MHz, CDCl3) δ −61.2 (s). IR (KBr) 2994, 2924, 2850, 1769, 1382, 1277, 1245, 1136, 1057, 772. HRMS (ESI-TOF) m/z [M − I]+ Calcd for (C18H25F6N2O)+ 399.1866; found 399.1863. [α]23.6D = −11.9 (c = 0.6, CHCl3). (2S,3S)-2-(3,5-Bis(trifluoromethyl)benzamido)-N-(3,5-bis(trifluoromethyl)benzyl)-N,N,3-trimethylpentan-1-aminium bromide (3d). 75 mg, yield 79%, white solid, mp 100−101 °C. 1H NMR (400 MHz, CDCl3) δ 9.20 (d, J = 8.0 Hz, 1H), 8.78 (s, 2H), 8.27 (s, 2H), 7.99 (s, 1H), 7.91 (s, 1H), 5.49 (d, J = 12.4 Hz, 1H), 5.22−5.29 (m, 2H), 4.74 (br, 1H), 4.10 (d, J = 13.6 Hz, 1H), 3.28 (s, 6H), 1.89 (s, 1H), 1.58 (br, 1H), 1.24−1.32 (m, 1H), 1.04 (d, J = 6.8 Hz, 3H), 0.88 (t, J = 6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 164.2, 134.8, 133.3, 132.8 (q, J = 34.0 Hz), 131.7 (q, J = 33.7 Hz), 132.2 (q, J = 34.0 Hz), 129.9, 128.6, 125.3, 124.8, 123.0 (q, J = 271.6 Hz), 122.5 (q, J = 273.8 Hz), 65.8, 65.4, 49.6, 49.4, 48.8, 39.6, 25.2, 14.9, 11.3. 19F NMR (376 MHz, CDCl3) δ −62.7 (s), −63.1 (s). IR (KBr) 3188, 2966, 2928, 2876, 1660, 1627, 1543, 1465, 1371, 1345, 1279, 1179, 1137, 910, 843, 749, 682. HRMS (ESI-TOF) m/z [M − Br]+ Calcd for (C26H27F12N2O)+ 611.1926; found 611.1942. [α]24.1D = +4.3 (c = 0.3, CHCl3). (S )-2-(3,5-Bi s(tri fluoro methyl) benza mi do)-N-(3,5-bis(trifluoromethyl)benzyl)-N,N-dimethyl-3-phenylpropan-1-aminium bromide (3e). 81 mg, yield 80%, white solid, mp 77−78 °C. 1H NMR (400 MHz, CDCl3) δ 10.07 (d, J = 7.2 Hz, 1H), 8.66 (s, 2H), 8.16 (s, 2H), 7.94 (s, 1H), 7.87 (s, 1H), 7.10−7.26 (m, 5H), 5.19 (dd, J = 12.4 4844

DOI: 10.1021/acs.joc.7b00571 J. Org. Chem. 2017, 82, 4840−4850

Article

The Journal of Organic Chemistry

(2S,3S)-2-(3,5-Bis(trifluoromethyl)benzamido)-N-(2,4-bis(trifluoromethyl)benzyl)-N,N,3-trimethylpentan-1-aminium fluoride (3j). 90 mg, yield 80%, white solid, mp 63−64 °C. 1H NMR (400 MHz, CDCl3) δ 8.48 (s, 2H), 8.12 (d, J = 8.8 Hz, 1H), 8.05 (s, 2H), 7.96−7.99 (m, 2H), 5.02 (d, J = 13.6 Hz, 1H), 4.89 (d, J = 13.6 Hz, 1H), 4.74−4.76 (br, 1H), 4.38−4.44 (br, 1H), 3.75 (d, J = 13.6 Hz,1H), 3.13 (s, 6H), 1.83 (br, 1H), 1.54 (br, 1H), 1.24−1.29 (br, 1H), 1.01 (d, J = 6.4 Hz, 3H), 0.92 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 164.5, 137.3, 134.8, 134.0 (q, J = 34.1 Hz), 132.2 (q, J = 32.3 Hz), 131.9 (q, J = 33.8 Hz), 129.7, 128.4, 128.0, 127.0, 125.5, 125.2, 122.8 (q, J = 273.2 Hz), 122.9 (q, J = 271.7 Hz), 122.5 (q, J = 271.7 Hz), 68.8, 64.0, 50.6, 50.1, 49.3, 39.7, 24.8, 14.7, 11.3. 19F NMR (376 MHz, CDCl3) δ −56.4 (s), −63.1 (s), −63.7 (s), −147.2 (s). IR (KBr) 3187, 3052, 2980, 1653, 1610, 1540, 1478, 1470, 1355, 1290, 1144, 1065, 910, 852, 767, 711, 680, 415. HRMS (ESI-TOF) m/z [M − F]+ calcd for (C26H27F12N2O)+ 611.1926; found 611.1926. [α]23.4D = +3.3 (c = 0.13, CHCl3). N-((2S,3S)-1-(Dimethylamino)-3-methylpentan-2-yl)-3,5-bis(trifluoromethyl)benzamide (3k). 82 mg, yield 77%, white solid, mp 126−127 °C. 1H NMR (400 MHz, CDCl3) δ 8.57 (s, 2H), 8.15 (d, J = 7.6 Hz, 1H), 7.98 (s, 1H), 4.37−4.42 (m, 1H), 3.42 (t, J = 12.0 Hz, 1H), 2.72 (dd, J = 4.0 Hz, J = 12.6 Hz, 1H), 2.63 (s, 6H), 1.87−1.93 (m, 1H), 1.49−1.56 (m, 1H), 1.17−1.26 (m, 1H), 0.94−0.98 (m, 6H). 13 C NMR (100 MHz, CDCl3) δ 164.9, 137.2, 132.0 (q, J = 33.6 Hz), 127.4, 124.7, 123.0 (q, J = 271.2 Hz), 58.3, 51.9, 45.5, 38.6, 36.9, 25.7, 14.6, 11.9. 19F NMR (376 MHz, CDCl3) δ −62.8 (s). IR (KBr) 3236, 3067, 2966, 1644, 1548, 1462, 1383, 1306, 1279, 1183, 1130, 907, 846, 701, 681, 433. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C17H23F6N2O 385.1715; found 385.1707. [α]23.0D = +29.7 (c = 1.4, CHCl3). (2S,3S)-N-(2,4-Bis(trifluoromethyl)benzyl)-N,N,3-trimethyl-2-(Nmethyl-3,5-bis(trifluoromethyl)benzamido)pentan-1-aminium bromide (3l). 79 mg, yield 80%, white solid, mp 89−90 °C. 1H NMR (400 MHz, CDCl3) δ 8.62 (d, J = 8.0 Hz, 1H), 7.95−8.06 (m, 5H), 5.63 (d, J = 13.2 Hz, 1H), 5.51 (d, J = 13.6 Hz, 1H), 5.10−5.15 (m, 2H), 3.96 (d, J = 13.2 Hz, 1H), 3.51 (s, 3H), 3.30 (s, 3H), 3.22 (s, 3H), 1.86 (s, 1H), 1.48 (br, 1H), 1.20−1.30 (m, 4H), 0.97 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 169.4, 138.6, 137.4, 133.7 (q, J = 34.1 Hz), 132.3 (q, J = 30.8 Hz), 132.2 (q, J = 34.0 Hz), 129.4, 128.9, 127.4, 124.9, 124.0, 123.1 (q, J = 272.0 Hz), 122.8 (q, J = 271.4 Hz), 122.6 (q, J = 271.4 Hz), 66.3, 62.4, 53.3, 49.9, 35.2, 33.6, 24.7, 19.1, 16.6, 10.6. 19F NMR (376 MHz, CDCl3) δ −57.9 (s), −64.8 (s), −65.4 (s). IR (KBr) 2970, 2933, 2876, 1638, 1486, 1466, 1410, 1370, 1343, 1308, 1281, 1179, 1135, 1057, 907, 849, 733, 681. HRMS (ESITOF) m/z [M − Br]+ Calcd for (C27H29F12N2O)+ 625.2083; found 625.2077. [α]25.8D = −3.3 (c = 3.0, CHCl3). General Procedure for the Product 4. To a solution of the catalyst 3i (0.01 mmol, 0.1 equiv), KF (0.2 mmol, 2.0 equiv) and 3substituted oxindole 1 (0.1 mmol, 1.0 equiv) in toluene (1.0 mL) was added (Z)-β-chloro-1-phenylpropenone (Z)-2 (0.12 mmol, 1.2 equiv) at room temperature. The solvent was removed after the reaction was finished (monitored by TLC analysis), and the residue was purified directly by column chromatography on silica gel chromatography (hexane/ethyl acetate = 9/1) to afford 4. tert-Butyl (S,Z)-2-oxo-3-(3-oxo-3-phenylprop-1-en-1-yl)-3-phenylindoline-1-carboxylate (4a). 38 mg, 87% yield, white solid, mp 103−105 °C. 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8 Hz, 1H), 7.76−7.78 (m, 2H), 7.49 (t, J = 7.2 Hz, 1H), 7.31−7.39 (m, 3H), 7.21−7.25 (m, 6H), 7.11−7.15 (m, 1H), 7.00 (d, J = 12 Hz, 1H), 6.69 (d, J = 12 Hz, 1H),1.59 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 190.1, 173.5, 149.6, 144.0, 141.3, 140.9, 137.2, 133.0, 129.4, 128.8, 128.7, 128.5, 128.4, 127.9, 127.6, 127.5, 124.9, 124.3, 115.2, 83.9, 58.9, 28.1. IR (KBr) 3057, 2980, 2931, 1770, 1727, 1668, 1598, 1478, 1369, 1290, 1249, 1148, 1004, 844, 737, 696. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for C28H25NNaO4 462.1681; found 462.1680. [α]25.8D = −84.8 (c = 1.0, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/ Hexane = 10:90, 254 nm, 1.0 mL/min): major 8.0 min, minor 12.0 min. Enantiomeric excess: 88%. tert-Butyl (S,Z)-5-methoxy-2-oxo-3-(3-oxo-3-phenylprop-1-en-1yl)-3-phenylindoline-1-carboxylate (4b). 37.6 mg, yield 80%, white

Hz, J = 14.4 Hz, 2H), 5.06 (t, J = 11.2 Hz, 1H), 4.93 (br, 1H), 3.60 (d, J = 12.8 Hz, 1H), 3.25−3.28 (m, 4H), 2.98−3.05 (m, 4H). 13C NMR (100 MHz, CDCl3) δ 164.5, 136.0, 134.9, 133.2, 132.8 (q, J = 33.9 Hz), 131.6 (q, J = 33.7 Hz), 129.7, 129.2, 128.8, 128.5, 127.3, 125.2, 124.7, 123.0 (q, J = 271.6 Hz), 122.5 (q, J = 271.8 Hz), 66.8, 66.0, 50.5, 49.2, 47.7, 39.9. 19F NMR (376 MHz, CDCl3) δ −62.8 (s), −63.0 (s). IR (KBr) 3187, 3027, 2928, 1659, 1620, 1547, 1483, 1462, 1373, 1338, 1279, 1218, 1181, 1134, 909, 844, 771, 701, 682, 418. HRMS (ESI-TOF) m/z [M − Br]+ Calcd for (C29H25F12N2O)+ 645.1770; found 645.1767. [α]22.2D = −18.0 (c = 0.7, CHCl3). ( S)-2-(3 ,5 -Bis(t rifluo romethyl )benzamido) -N-(3 ,5 -bi s(trifluoromethyl)benzyl)-N,N,3,3-tetramethylbutan-1-aminium bromide (3f). 81 mg, yield 81%, white solid, mp 149−150 °C. 1H NMR (400 MHz, CDCl3) δ 9.54 (d, J = 8.4 Hz, 1H), 8.81 (s, 2H), 8.26 (s, 2H), 8.00 (s, 1H), 7.89 (s, 1H), 5.55 (d, J = 12.4 Hz, 1H), 5.23−5.29 (m, 2H), 4.61 (t, J = 8.8 Hz, 1H), 4.41 (d, J = 14.0 Hz, 1H), 3.25 (s, 3H), 3.23 (s, 3H), 1.09 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 164.8, 134.8, 133.4, 132.8 (q, J = 33.9 Hz), 131.5 (q, J = 33.6 Hz), 130.1, 128.8, 125.2, 124.7, 123.0 (q, J = 271.5 Hz), 122.5 (q, J = 271.7 Hz), 66.1, 65.7, 53.0, 48.7, 48.1, 36.9, 26.2. 19F NMR (376 MHz, CDCl3) δ −62.7 (s), −63.0 (s). IR (KBr) 2967, 2933, 1659, 1547, 1467, 1372, 1279, 1219, 1182, 1134, 909, 772, 700, 404. HRMS (ESITOF) m/z [M − Br]+ Calcd for (C26H27F12N2O)+ 611.1926; found 611.1926. [α]22.2D = +6.8 (c = 0.7, CHCl3). (2S,3S)-N-(3,5-Bis(trifluoromethyl)benzyl)-N,N,3-trimethyl-2-(4methylbenzamido)pentan-1-aminium bromide (3g). 75 mg, yield 77%, white solid, mp 112−113 °C. 1H NMR (400 MHz, CDCl3) δ 8.48 (d, J = 8.8 Hz, 1H), 8.30 (s, 2H), 7.99−8.02 (m, 2H), 7.14 (d, J = 8.0 Hz, 2H), 5.46 (d, J = 12.8 Hz, 1H), 5.29 (d, J = 12.4 Hz, 1H), 5.12 (t, J = 11.2 Hz, 1H), 4.74 (br, 1H), 3.92 (d, J = 13.6 Hz, 1H), 3.32 (s, 3H), 3.30 (s, 3H), 2.31 (s, 3H), 1.87 (s, 1H), 1.57 (br, 1H), 1.26−1.33 (m, 1H), 1.03 (d, J = 6.4 Hz, 3H), 0.89 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 167.5, 142.5, 133.4, 132.7 (q, J = 33.9 Hz), 130.2, 130.1, 129.1, 127.8, 124.6, 122.6 (q, J = 271.6 Hz), 66.2, 65.6, 50.1, 49.2, 49.0, 39.4, 25.2, 21.3, 15.3, 11.3. 19F NMR (376 MHz, CDCl3) δ −62.9 (s). IR (KBr) 2994, 1769, 1758, 1372, 1245, 1220, 1180, 1138, 1056, 772, 682. HRMS (ESI-TOF) m/z [M − Br]+ Calcd for (C25H31F6N2O)+ 489.2335; found 489.2342. [α]24.0D = +5.6 (c = 1.4, CHCl3). (2S,3S)-2-(3,5-Bis(trifluoromethyl)benzamido)-N-(3,5-dimethoxybenzyl)-N,N,3-trimethylpentan-1-aminium bromide (3h). 82 mg, yield 81%, white solid, mp 115−116 °C. 1H NMR (400 MHz, DMSOd6) δ 9.17 (d, J = 8.8 Hz, 1H), 8.53 (s, 2H), 8.37 (s, 1H), 6.78 (br, 2H), 6.69 (s, 1H), 4.54−4.64 (m, 3H), 3.70−3.84 (m, 8H), 3.10 (s, 3H), 2.98 (s, 3H), 1.76 (s, 1H), 1.49−1.52 (br, 1H), 1.20−1.27 (m, 1H), 0.97 (d, J = 6.4 Hz, 3H), 0.82 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, DMSO-d6) δ 163.7, 161.0, 136.5, 131.0 (q, J = 33.1 Hz), 130.2, 128.7, 125.8, 123.6 (q, J = 271.4 Hz), 111.7, 102.3, 66.6, 66.0, 55.9, 50.2, 49.8, 49.1, 24.8, 15.3, 11.7. 19F NMR (376 MHz, CDCl3) δ −61.2 (s). IR (KBr) 2964, 2928, 1660, 1598, 1543, 1462, 1326, 1279, 1208, 1135, 1068, 845, 771, 700, 681. HRMS (ESI-TOF) m/z [M − Br]+ Calcd for (C26H33F6N2O3)+ 535.2390; found 535.2391. [α]25.7D = +4.4 (c = 0.2, CHCl3). (2S,3S)-2-(3,5-Bis(trifluoromethyl)benzamido)-N-(2,4-bis(trifluoromethyl)benzyl)-N,N,3-trimethylpentan-1-aminium bromide (3i). 81 mg, yield 80%, white solid, mp 149−150 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.27 (br, 1H), 8.77 (s, 2H), 8.17− 8.30 (m, 4H), 5.13 (d, J = 13.2 Hz, 1H), 4.97 (d, J = 13.2 Hz, 1H), 4.57 (d, J = 8.0 Hz, 2H), 3.94 (d, J = 10.8 Hz, 1H), 3.18 (s, 3H),3.10 (s, 3H), 1.80−1.82 (br, 1H), 1.52 (br, 1H), 1.26 (br, 1H), 0.88−0.96 (m, 6H). 13C NMR (100 MHz, CDCl3) δ 164.2, 137.8, 133.7 (q, J = 34.1 Hz), 132.4 (q, J = 30.9 Hz), 131.6 (q, J = 33.6 Hz), 129.3, 128.8, 128.7, 125.2, 125.0, 123.0 (q, J = 271.8 Hz), 122.9 (q, J = 273.3 Hz), 122.5 (q, J = 271.7 Hz), 66.5, 63.1, 50.4, 49.7, 49.3, 39.7, 25.3, 15.0, 11.4. 19F NMR (376 MHz, CDCl3) δ −56.1 (s), −62.7 (s), −63.5 (s). IR (KBr) 3194, 3046, 2967, 1662, 1620, 1541, 1483, 1462, 1344, 1280, 1134, 1058, 910, 845, 770, 700, 681, 418. HRMS (ESI) m/z [M − Br]+ Calcd for (C26H27F12N2O)+ 611.1926; found 611.1950. [α]22.5D = +4.2 (c = 1.3, CHCl3). 4845

DOI: 10.1021/acs.joc.7b00571 J. Org. Chem. 2017, 82, 4840−4850

Article

The Journal of Organic Chemistry solid, mp 50−52 °C. 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.8 Hz, 1H), 7.78 (d, J = 7.2 Hz, 2H), 7.50 (t, J = 7.6 Hz, 1H), 7.37 (t, J = 8.0 Hz, 2H), 7.56 (br, 5H), 6.99 (d, J = 12.0 Hz, 1H), 6.84 (dd, J = 2.8 Hz, 8.4 Hz, 1H), 6.78 (d, J = 2.8 Hz, 1H), 6.67 (d, J = 12.0 Hz, 1H), 3.73 (s, 3H), 1.60 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 191.0, 173.6, 156.6, 149.6, 143.6, 141.1, 137.0, 134.3, 133.0, 130.4, 128.7, 128.4, 128.3, 127.9, 127.8, 127.5, 116.1, 113.7, 111.0, 83.8, 59.2, 55.5, 28.1. IR (KBr) 2984, 2928, 1765, 1725, 1665, 1597, 1490, 1448, 1277, 1151, 1006, 734. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C29H28NO5 470.1967; found 470.1959. [α]25.8D = −57.4 (c = 0.7, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 10:90, 254 nm, 1.0 mL/min): major 10.5 min, minor 21.6 min. Enantiomeric excess: 90%. tert-Butyl (S,Z)-5-methyl-2-oxo-3-(3-oxo-3-phenylprop-1-en-1yl)-3-phenylindoline-1-carboxylate (4c). 37.7 mg, yield 83%, white solid, mp 50−52 °C. 1H NMR (400 MHz, CDCl3) δ 7.76−7.79 (m, 3H), 7.49 (t, J = 7.6 Hz, 1H), 7.37 (t, J = 7.6 Hz, 2H), 7.23−7.26 (m, 5H), 7.11 (d, J = 8.0 Hz, 1H), 7.00 (s, 1H), 6.97 (d, J = 12 Hz, 1H), 6.66 (d, J = 12.0 Hz, 1H), 2.27 (s, 3H), 1.59 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 191.0, 173.7, 149.6, 143.7, 141.3, 138.4, 137.0, 133.9, 133.0, 129.3, 129.2, 128.7, 128.4, 128.3, 127.9, 127.7, 127.5, 125.6, 115.0, 83.8, 58.9, 28.1, 21.1. IR (KBr) 3056, 2980, 2930, 1794, 1768, 1729, 1668, 1601, 1504, 1478, 1464, 1369, 1344, 1303, 1290, 1249, 1232, 1148, 1005, 849, 831, 737, 412. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C29H28NO4 454.2018; found 454.2012. [α]25.2D = −55.0 (c = 0.75, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 10:90, 254 nm, 1.0 mL/min): major 8.5 min, minor 17.5 min. Enantiomeric excess: 90%. tert-Butyl (S,Z)-5-fluoro-2-oxo-3-(3-oxo-3-phenylprop-1-en-1-yl)3-phenylindoline-1-carboxylate (4d). 39 mg, yield 85%, yellow solid, mp 57−59 °C. 1H NMR (400 MHz, CDCl3) δ 7.95 (q, J = 4.4 Hz, 1H), 7.79 (d, J = 7.2 Hz, 2H), 7.51 (t, J = 7.6 Hz, 1H), 7.39 (t, J = 7.6 Hz, 2H), 7.22−7.29 (m, 5H), 7.02−7.08 (m, 2H), 6.96 (dd, J = 2.8 Hz, 7.6 Hz, 1H), 6.67 (d, J = 12.0 Hz, 1H), 1.58 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 190.5, 173.1, 159.7 (d, J = 242.3 Hz), 149.6, 143.8, 140.8, 137.0, 136.9 (d, J = 2.5 Hz), 133.2, 130.9 (d, J = 8.3 Hz), 128.8, 128.5, 128.4, 128.1, 127.8, 127.3, 116.5 (d, J = 7.8 Hz), 115.2 (d, J = 22.6 Hz), 112.2 (d, J = 24.6 Hz), 84.1, 58.9, 28.1. 19F NMR (376 MHz, CDCl3) δ −117.9 (m). IR (KBr) 2979, 2926, 1768, 1727, 1668, 1602, 1509, 1478, 1464, 1393, 1368, 1345, 1301, 1249, 1232, 1148, 1004, 846, 752, 736, 688, 593, 469, 404. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C28H25FNO4 458.1768; found 458.1760. [α]24.2D = −78.1 (c = 0.80, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/ Hexane = 20:80, 254 nm, 1.0 mL/min): major 5.2 min, minor 6.8 min. Enantiomeric excess: 86%. tert-Butyl (S,Z)-5-chloro-2-oxo-3-(3-oxo-3-phenylprop-1-en-1-yl)3-phenylindoline-1-carboxylate (4e). 38.8 mg, yield 82%, white solid, mp 62−64 °C. 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.8 Hz, 1H), 7.80 (d, J = 7.2 Hz, 2H), 7.52 (t, J = 7.6 Hz, 1H), 7.40 (t, J = 7.6 Hz, 2H), 7.22−7.33 (m, 6H), 7.18 (d, J = 2.0 Hz, 1H), 7.07 (d, J = 12 Hz, 1H), 6.66 (d, J = 12 Hz, 1H), 1.58 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 190.6, 172.8, 149.5, 143.7, 140.8, 139.6, 137.1, 133.2, 131.1, 129.7, 128.9, 128.7, 128.5, 128.4, 128.2, 127.9, 127.4, 124.9, 116.5, 84.3, 58.7, 28.1. IR (KBr) 3060, 2980, 2931, 1773, 1730, 1669, 1597, 1475, 1448, 1394, 1336, 1294, 1252, 1233, 1150, 1115, 1006, 844, 821, 734, 695, 404. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C28H25ClNO4 474.1472; found 474.1464. [α]24.3D = −55.4 (c = 0.75, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 20:80, 254 nm, 1.0 mL/min): major 4.9 min, minor 6.6 min. Enantiomeric excess: 85%. tert-Butyl (S,Z)-2-oxo-3-(3-oxo-3-phenylprop-1-en-1-yl)-3-phenyl-5-(trifluoromethoxy)indoline-1-carboxylate (4f). 40.9 mg, yield 78%, white solid, mp 113−115 °C. 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 8.8 Hz, 1H), 7.78−7.80 (m, 2H), 7.52 (t, J = 7.2 Hz, 1H), 7.39 (t, J = 8.0 Hz, 2H), 7.20−7.30 (m, 6H), 7.09 (d, J = 12.0 Hz, 1H), 6.68 (d, J = 12.0 Hz, 1H), 1.59 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 190.5, 172.9, 149.5, 145.7, 143.8, 140.7, 139.5, 137.0, 133.2, 131.0, 128.9, 128.5, 128.4, 128.2, 128.0, 127.3, 121.4, 120.0 (q, J = 255.0 Hz), 117.9, 116.3, 84.4, 58.8, 28.1. 19F NMR (376 MHz, CDCl3) δ −58.2 (s). IR (KBr) 3066, 3002, 2924, 1775, 1732, 1665, 1600, 1488, 1453,

1347, 1302, 1252, 1142, 1000, 771, 741, 691. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C29H25F3NO5 (M+H)+ 524.1685; found 524.1679. [α]25.2D = −63.7 (c = 1.70, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 10:90, 254 nm, 1.0 mL/min): major 4.7 min, minor 6.0 min. Enantiomeric excess: 87%. tert-Butyl (S,Z)-3-(4-fluorophenyl)-2-oxo-3-(3-oxo-3-phenylprop1-en-1-yl)indoline-1-carboxylate (4g). 38 mg, yield 84%, white solid, mp 83−85 °C. 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 8.0 Hz, 1H), 7.77 (d, J = 7.6 Hz, 2H), 7.51 (t, J = 7.6 Hz, 1H), 7.33−7.40 (m, 3H), 7.20−7.27 (m, 3H), 7.16 (t, J = 7.6 Hz, 1H), 7.00 (d, J = 12.0 Hz, 1H), 6.93 (t, J = 8.8 Hz, 2H), 6.63 (d, J = 12.0 Hz, 1H), 1.60 (s, 9H). 13 C NMR (100 MHz, CDCl3) δ 190.8, 173.6, 162.5 (d, J = 246.1 Hz), 149.5, 143.6, 140.8, 137.1, 136.8 (d, J = 3.1 Hz), 133.1, 129.4 (d, J = 8.1 Hz), 129.2, 128.9, 128.4, 128.3, 127.8, 125.0, 124.4, 115.5 (d, J = 21.4 Hz), 115.4, 84.1, 58.3, 28.1. 19F NMR (376 MHz, CDCl3) δ −114.4 (m). IR (KBr) 3062, 2980, 2924, 1768, 1728, 1666, 1607, 1484, 1449, 1369, 1345, 1266, 1250, 1144, 1005, 994, 821, 733, 695, 414. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for C28H24FNNaO4 480.1587; found 480.1592. [α]24.3D = −105.3 (c = 0.80, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane= 20:80, 254 nm, 1.0 mL/min): major 5.0 min, minor 6.8 min. Enantiomeric excess: 83%. tert-Butyl (S,Z)-2-oxo-3-(3-oxo-3-phenylprop-1-en-1-yl)-3-(ptolyl)indoline-1-carboxy-late (4h). 39 mg, yield 86%, white solid, mp 105−107 °C. 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.0 Hz, 1H), 7.77 (d, J = 7.2 Hz, 2H), 7.48 (t, J = 7.6 Hz, 1H), 7.30−7.38 (m, 3H), 7.20 (d, J = 7.2 Hz, 1H), 7.11−7.14 (m, 3H), 7.06 (d, J = 8.4 Hz, 2H), 6.98 (d, J = 12.0 Hz, 1H), 6.67 (d, J = 12.0 Hz, 1H), 2.28 (s, 3H), 1.59 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 190.8, 173.6, 149.6, 144.3, 140.8, 138.3, 137.7, 137.1, 133.0, 129.5, 129.4, 128.6, 128.4, 128.3, 127.4, 124.8, 124.3, 115.2, 83.8, 58.5, 28.1, 21.0. IR (KBr) 3053, 2963, 1768, 1727, 1665, 1606, 1478, 1464, 1447, 1393, 1345, 1252, 1148, 1009, 800, 750, 697, 475. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C29H28NO4 454.2018; found 454.2012. [α]25.2D = −114.2 (c = 0.53, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 10:90, 254 nm, 1.0 mL/min): major 7.7 min, minor 14.1 min. Enantiomeric excess: 88%. tert-Butyl (S,Z)-3-(4-methoxyphenyl)-2-oxo-3-(3-oxo-3-phenylprop-1-en-1-yl)indo-line-1-carboxylate (4i). 36.7 mg, yield 78%, white solid, mp 53−55 °C. 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.0 Hz, 1H), 7.77 (d, J = 7.2 Hz, 2H), 7.49 (t, J = 7.6 Hz, 1H), 7.31− 7.39 (m, 3H), 7.22−7.25 (m, 1H), 7.11−7.16 (m, 3H), 6.98 (d, J = 12.0 Hz, 1H), 6.77 (d, J = 8.8 Hz, 2H), 6.65 (d, J = 12.0 Hz, 1H), 3.73 (s, 3H), 1.59 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 191.0, 173.9, 159.3, 149.6, 144.3, 140.8, 137.2, 133.2, 133.0, 129.6, 128.8, 128.7, 128.5, 128.4, 127.5, 124.9, 124.3, 115.2, 114.1, 83.9, 58.2, 55.3, 28.1. IR (KBr) 2977, 2928, 1768, 1727, 1668, 1610, 1478, 1465, 1449, 1394, 1368, 1291, 1249, 1150, 1010, 737, 423. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C29H28NO5 470.1967; found 470.1962. [α]25.6D = −87.0 (c = 0.6, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 10:90, 254 nm, 1.0 mL/min): major 11.5 min, minor 24.4 min. Enantiomeric excess: 88%. tert-Butyl (S,Z)-3-(3-methoxyphenyl)-2-oxo-3-(3-oxo-3-phenylprop-1-en-1-yl)indo-line-1-carboxylate (4j). 39 mg, yield 83%, white solid, mp 57−58 °C. 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 7.6 Hz, 2H), 7.49 (t, J = 7.6 Hz, 1H), 7.30−7.39 (m, 3H), 7.23 (t, J = 8.0 Hz, 1H), 7.18 (t, J = 8.0 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 7.00 (d, J = 12.0 Hz, 1H),6.77−6.82 (m, 3H), 6.68 (d, J = 12.0 Hz, 1H), 3.71 (s, 3H), 1.60 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 190.7, 173.4, 159.7, 149.5, 144.0, 142.7, 140.8, 137.1, 133.0, 129.6, 129.3, 128.7, 128.4, 128.3, 127.4, 124.9, 124.3, 119.8, 115.2, 113.8, 113.0, 83.9, 58.8, 55.2, 28.1. IR (KBr) 2979, 2934, 2835, 1769, 1728, 1667, 1601, 1581, 1479, 1464, 1448, 1393, 1291, 1149, 1050, 1005, 843, 752, 736, 688. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C29H28NO5 470.1967; found 470.1959. [α]24.6D = −94.3 (c = 0.6, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane= 5:95, 254 nm, 0.7 mL/min): major 24.4 min, minor 27.5 min. Enantiomeric excess: 90%. tert-Butyl (S,Z)-5-methyl-2-oxo-3-(3-oxo-3-phenylprop-1-en-1yl)-3-(p-tolyl)indo-line-1-carboxylate (4k). 42 mg, yield 90%, white solid, mp 59−60 °C. 1H NMR (400 MHz, CDCl3) δ 7.76−7.79 (m, 4846

DOI: 10.1021/acs.joc.7b00571 J. Org. Chem. 2017, 82, 4840−4850

Article

The Journal of Organic Chemistry

tert-Butyl (S,Z)-3-(3-(4-nitrophenyl)-3-oxoprop-1-en-1-yl)-2-oxo3-phenylindoline-1-carboxylate (4p). 34.8 mg, yield 72%, white solid, mp 69−71 °C. 1H NMR (400 MHz, CDCl3) δ 8.22−8.25 (m, 2H), 7.92−7.94 (m, 3H), 7.37 (dt, J = 1.6 Hz, 8.0 Hz, 1H), 7.27−7.30 (m, 3H), 7.20−7.24 (m, 3H), 7.17 (dt, J = 0.8 Hz, 7.2 Hz, 1H), 6.98 (d, J = 12.0 Hz, 1H), 6.80 (d, J = 12.0 Hz, 1H), 1.59 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 189.4, 173.4, 150.3, 149.4, 146.1, 141.5, 140.9, 140.8, 129.4, 129.0, 128.9, 128.8, 128.2, 127.4, 126.6, 124.9, 124.5, 123.4, 115.3, 84.3, 59.0, 28.1. IR (KBr) 2980, 2928, 2854, 1791, 1767, 1730, 1672, 1601, 1526, 1477, 1464, 1369, 1345, 1289, 1249, 1223, 1148, 1005, 834, 736, 402. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for C28H24N2NaO6 507.1532; found 507.1530. [α]24.3D = −76.4 (c = 0.78, CHCl3) HPLC (Daicel Chiralpak IC, i-PrOH/Hexane = 10:90, 220 nm, 0.5 mL/min): major 67.7 min, minor 76.2 min. Enantiomeric excess: 84%. tert-Butyl (S,Z)-2-oxo-3-(3-oxo-3-(thiophen-2-yl)prop-1-en-1-yl)3-phenylindoline-1-carboxylate (4q). 37 mg, yield 83%, yellow solid, mp 40−42 °C. 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.4 Hz, 1H), 7.64 (dd, J = 0.8 Hz, 3.6 Hz, 1H), 7.57 (dd, J = 0.8 Hz, 4.8 Hz, 1H), 7.36 (dt, J = 1.6 Hz, 7.2 Hz, 1H), 7.14−7.30 (m, 7H), 7.06 (dd, J = 4.0 Hz, 4.8 Hz, 1H), 6.96 (d, J = 12.0 Hz, 1H), 6.67 (d, J = 12.0 Hz, 1H), 1.61 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 182.1, 173.2, 149.7, 145.0, 144.8, 141.5, 141.0, 134.2, 132.3, 129.3, 128.7, 128.6, 128.0, 127.9, 127.5, 126.5, 124.6, 124.3, 115.3, 83.9, 58.9, 28.1. IR (KBr) 2979, 2920, 1771, 1728, 1652, 1558, 1540, 1477, 1418, 1345, 1289, 1247, 1148, 1004, 749, 696. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C26H24NO4S 446.1426; found 446.1417. [α]25.6D = −35.8 (c = 0.80, CHCl3) HPLC (Daicel Chiralpak AD-H, i-PrOH/Hexane = 10:90, 220 nm, 1.0 mL/min): major 15.8 min, minor 20.1 min. Enantiomeric excess: 85%. tert-Butyl (S,Z)-3-(3-(naphthalen-1-yl)-3-oxoprop-1-en-1-yl)-2oxo-3-phenylindoline-1-carboxylate (4r). 40.6 mg, yield 83%, yellow solid, mp 50−51 °C. 1H NMR (400 MHz, CDCl3) δ 8.33−8.35 (m, 1H), 7.92 (dd, J = 5.6 Hz, 8.0 Hz, 2H), 7.80−7.82 (m, 2H), 7.47−7.50 (m, 2H), 7.43 (dd, J = 7.6 Hz, 8.0 Hz, 1H), 7.23−7.33 (m, 7H), 7.16 (dt, J = 0.8 Hz, 7.6 Hz, 1H), 6.98 (d, J = 11.6 Hz, 1H), 6.72 (d, J = 11.6 Hz, 1H), 1.54 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 193.5, 173.6, 149.6, 144.4, 141.7, 141.1, 135.4, 133.8, 132.9, 130.2, 130.1, 129.4, 129.0, 128.8, 128.7, 128.2, 128.0, 127.7, 127.5, 126.4, 126.1, 124.6, 124.4, 124.3, 115.3, 83.9, 58.8, 28.1. IR (KBr) 3053, 2979, 2929, 1792, 1768, 1728, 1666, 1597, 1508, 1490, 1477, 1463, 1393, 1368, 1344, 1302, 1249, 1148, 1081, 1003, 785, 751, 696, 467. EI-MS (m/z) 489(M)+ 389 (100%), 261 (19.75%), 193 (23.94%), 155 (89.21%), 127 (44.6%). HRMS (EI) m/z [M]+ Calcd for C32H27NO4 489.1940; found 489.1948. [α]25.6D = −60.5 (c = 0.80, CHCl3) HPLC (Daicel Chiralpak AD-H, i-PrOH/Hexane = 10:90, 220 nm, 1.0 mL/min): major 9.7 min, minor 8.2 min. Enantiomeric excess: 88%. tert-Butyl (S,Z)-3-(3-(4-bromophenyl)-3-oxoprop-1-en-1-yl)-5methyl-2-oxo-3-phenylindoline-1-carboxylate (4s). 37 mg, yield 70%, white solid, mp 51−52 °C. 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 7.6 Hz, 2H), 7.25 (br, 5H), 7.12 (d, J = 7.6 Hz, 1H), 6.99 (s, 1H), 6.90 (d, J = 12.0 Hz, 1H), 6.68 (d, J = 12.0 Hz, 1H), 2.28 (s, 3H), 1.59 (s, 9H). 13 C NMR (100 MHz, CDCl3) δ 190.2, 173.6, 149.5, 144.0, 141.2, 138.4, 135.9, 134.0, 131.7, 129.9, 129.4, 129.2, 128.7, 128.2, 127.9, 127.5, 127.3, 125.7, 115.0, 83.9, 59.0, 28.1, 21.0. IR (KBr) 2994, 1769, 1758, 1374, 1245, 1056, 401. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C29H27BrNO4 532.1123; found 532.1116. [α]24.4D = −31.3 (c = 0.5, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 20:80, 254 nm, 1.0 mL/min): major 6.6 min, minor 8.7 min. Enantiomeric excess: 86%. tert-Butyl (R,Z)-3-benzyl-2-oxo-3-(3-oxo-3-phenylprop-1-en-1yl)indoline-1-carboxylate (4t). 36 mg, yield 80%, white solid, mp 52−53 °C. 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.0 Hz, 2H), 7.43−7.48 (m, 2H), 7.31 (t, J = 7.6 Hz, 2H), 7.09−7.13 (m, 2H), 7.03−7.06 (m, 2H), 6.94−6.99 (m, 2H), 6.90 (t, J = 12.0 Hz, 1H), 6.77 (d, J = 7.2 Hz, 2H), 6.54 (d, J = 12.0 Hz, 1H), 3.35 (d, J = 12.8 Hz, 1H), 3.25 (d, J = 12.4 Hz, 1H), 1.55 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 190.9, 175.0, 148.8, 142.4, 140.6, 137.2, 134.0, 132.9, 130.1, 129.3, 128.3, 128.2, 127.6, 127.1, 123.7, 123.3, 114.6, 83.5, 55.6,

3H), 7.49 (t, J = 7.6 Hz, 1H), 7.37 (t, J = 7.6 Hz, 2H), 7.05−7.14 (m, 5H), 6.99 (s, 1H), 6.97 (d, J = 12.0 Hz, 1H), 6.65 (d, J = 12.0 Hz, 1H), 2.28 (s, 3H), 2.26 (s, 3H), 1.58 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 191.1, 173.8, 149.7, 143.7, 138.5, 138.4, 137.7, 137.2, 133.9, 133.0, 129.5, 129.4, 129.2, 128.5, 128.3, 127.7, 127.4, 125.6, 115.0, 83.7, 58.6, 28.1, 21.1, 21.0. IR (KBr) 2979, 2924, 1768, 1727, 1669, 1597, 1508, 1489, 1448, 1369, 1338, 1301, 1249, 1154, 1113, 1005, 818, 735, 412. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C30H30NO4 468.2175; found 468.2170. [α]25.2D = −46.8 (c = 1.60, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 10:90, 254 nm, 1.0 mL/min): major 8.4 min, minor 22.7 min. Enantiomeric excess: 89%. tert-Butyl (S,Z)-3-(4-(tert-butyl)phenyl)-2-oxo-3-(3-oxo-3-phenylprop-1-en-1-yl)-indoline-1-carboxylate (4l). 34.7 mg, yield 70%, yellow solid, mp 58−59 °C. 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.0 Hz, 1H), 7.77 (d, J = 7.2 Hz, 2H), 7.49 (t, J = 7.2 Hz, 1H), 7.31−7.40 (m, 3H), 7.24−7.27 (m, 3H), 7.12−7.17 (m, 3H), 6.99 (d, J = 12.0 Hz, 1H), 6.69 (d, J = 12.0 Hz, 1H), 1.60 (s, 9H), 1.25 (s, 9H). 13 C NMR (100 MHz, CDCl3) δ 190.9, 173.8, 150.8, 149.6, 144.1, 140.9, 138.2, 137.2, 133.0, 129.6, 128.7, 128.5, 128.4, 127.6, 127.2, 125.6, 125.0, 124.2, 115.2, 83.9, 58.6, 34.4, 31.2, 28.1. IR (KBr) 2963, 2859, 1767, 1728, 1666, 1600, 1478, 1463, 1449, 1368, 1345, 1290, 1249, 1149, 1004, 750, 736, 411. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C32H34NO4 496.2488; found 496.2481. [α]24.5D = −79.5 (c = 0.9, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 20:80, 254 nm, 1.0 mL/min): major 4.5 min, minor 5.6 min. Enantiomeric excess: 71%. tert-Butyl (S,Z)-2-oxo-3-(3-oxo-3-(p-tolyl)prop-1-en-1-yl)-3-phenylindoline-1-carboxylate (4m). 39 mg, yield 86%, white solid, mp 76−78 °C. 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.0 Hz, 1H), 7.67 (d, J = 8.0 Hz, 2H), 7.31−7.36 (m, 1H), 7.21−7.25 (m, 6H), 7.11−7.17 (m, 3H), 6.98 (d, J = 12.0 Hz, 1H), 6.65 (d, J = 12.0 Hz, 1H), 2.37 (s, 3H), 1.59 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 190.4, 173.6, 149.7, 143.8, 143.6, 141.4, 140.9, 134.8, 129.5, 129.1, 128.7, 128.6, 127.9, 127.7, 127.5, 124.9, 124.3, 115.2, 83.9, 58.9, 28.1, 21.7. IR (KBr) 2979, 2928, 1793, 1771, 1727, 1665, 1606, 1570, 1490, 1477, 1393, 1290, 1249, 1208, 1148, 1103, 1079, 1005, 843, 782, 750, 696, 472. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for C29H27NNaO4 476.1838; found 476.1818. [α]25.7D = −67.3 (c = 0.57, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 20:80, 254 nm, 1.0 mL/ min): major 6.4 min, minor 7.9 min. Enantiomeric excess: 86%. tert-Butyl (S,Z)-3-(3-(4-chlorophenyl)-3-oxoprop-1-en-1-yl)-2oxo-3-phenylindoline-1-carboxylate (4n). 35 mg, yield 75%, yellow solid, mp 56−58 °C. 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.0 Hz, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.32−7.35 (m, 3H), 7.20−7.27 (m, 6H), 7.14 (t, J = 7.2 Hz, 1H), 6.94 (d, J = 12 Hz, 1H), 6.69 (d, J = 12 Hz, 1H), 1.60 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 190.0, 173.5, 149.5, 144.3, 141.1, 140.8, 139.5, 135.5, 129.8, 129.3, 128.9, 128.8, 128.7, 128.0, 127.5, 127.2, 125.0, 124.3, 115.2, 84.1, 58.9, 28.1. IR (KBr) 3066, 2980, 2930, 1793, 1766, 1729, 1668, 1588, 1478, 1463, 1369, 1344, 1289, 1249, 1148, 1089, 1004, 786, 752, 696, 409. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for C28H24ClNaNO4 496.1292; found 496.1291. [α]24.3D = −63.4 (c = 0.8, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 20:80, 254 nm, 1.0 mL/min): major 6.1 min, minor 7.3 min. Enantiomeric excess: 84%. tert-Butyl (S,Z)-3-(3-(4-bromophenyl)-3-oxoprop-1-en-1-yl)-2oxo-3-phenylindoline-1-carboxylate (4o). 39 mg, yield 76%, yellow solid, mp 62−64 °C. 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.0 Hz, 1H), 7.62−7.64 (m, 2H), 7.50−7.52 (m, 2H), 7.34 (dt, J = 1.6 Hz, 8.0 Hz, 1H), 7.19−7.29 (m, 6H), 7.14 (dt, J = 0.8 Hz, 7.6 Hz, 1H), 6.94 (d, J = 12.0 Hz, 1H), 6.70 (d, J = 12.0 Hz, 1H), 1.60 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 189.9, 173.5, 149.5, 144.5, 141.1, 140.9, 135.9, 131.7, 129.9, 129.2, 128.9, 128.8, 128.3, 128.0, 127.5, 127.1, 125.0, 124.4, 115.3, 84.1, 58.9, 28.1. IR (KBr) 3056, 2979, 2930, 1793, 1768, 1728, 1667, 1598, 1584, 1478, 1464, 1369, 1344, 1302, 1289, 1249, 1148, 1071, 1002, 842, 784, 750, 696. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C28H25BrNO4 518.0967; found 518.0963. [α]24.4D = −55.6 (c = 1.90, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/ Hexane = 10:90, 254 nm, 1.0 mL/min): major 8.9 min, minor 11.2 min. Enantiomeric excess: 89%. 4847

DOI: 10.1021/acs.joc.7b00571 J. Org. Chem. 2017, 82, 4840−4850

Article

The Journal of Organic Chemistry

2H), 7.17−7.21 (m, 1H), 6.98−7.00 (m, 2H), 6.84 (d, J = 12 Hz, 1H), 6.42 (d, J = 12 Hz, 1H), 5.56−5.63 (m, 1H), 5.10 (d, J = 4.8 Hz, 1H), 5.07 (s, 1H), 2.66−2.74 (m, 2H), 1.64 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 191.0, 175.1, 149.4, 141.9, 140.3, 137.0, 133.0, 132.9, 130.8, 129.8, 128.3, 128.1, 127.6, 123.9, 123.1, 120.5, 114.8, 83.9, 53.8, 45.3, 28.1. IR (KBr) 3077, 2980, 2930, 1790, 1767, 1728, 1669, 1605, 1478, 1465, 1448, 1369, 1348, 1293, 1250, 1150, 1006, 924, 843, 752, 736, 689, 465. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for C25H25NNaO4 426.1681; found 426.1678. [α]25.2D = −4.0 (c = 0.45, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 20:80, 254 nm, 1.0 mL/ min): major 6.1 min, minor 8.1 min. Enantiomeric excess: 91%. tert-Butyl (R,Z)-3-(but-3-en-1-yl)-2-oxo-3-(3-oxo-3-phenylprop-1en-1-yl)indoline-1-carboxylate (4z). 35.5 mg, yield 85%, yellow oil. 1 H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 7.2 Hz, 2H), 7.46 (t, J = 7.2 Hz, 1H), 7.32 (t, J = 7.2 Hz, 2H), 7.18− 7.20 (m, 1H), 6.99−7.01 (m, 2H), 6.78 (d, J = 12 Hz, 1H), 6.35 (d, J = 12 Hz, 1H), 5.63−5.69 (m, 1H), 4.88−4.93 (m, 2H), 2.18 (dt, J = 4.8 Hz, 12 Hz, 1H), 2.03 (dt, J = 4.4 Hz, 12 Hz, 1H), 1.91−1.94 (m, 1H), 1.78−1.81 (m, 1H), 1.65 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 191.4, 175.3, 149.4, 142.1, 140.6, 137.0, 136.9, 132.9, 129.7, 128.4, 128.3, 127.9, 124.1, 123.1, 115.3, 114.8, 83.9, 53.8, 40.7, 28.2, 27.9. IR (KBr) 2978, 2927, 2853, 1792, 1767, 1728, 1669, 1640, 1478, 1465, 1483, 1348, 1292, 1249, 1150, 1005, 751, 736, 403. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C26H28NO4 418.2018; found 418.2010. [α]25.8D = 7.7 (c = 0.8, CHCl3) HPLC (Daicel Chiralpak PC-II, iPrOH/Hexane = 20:80, 254 nm, 1.0 mL/min): major 5.4 min, minor 6.9 min. Enantiomeric excess: 91%. tert-Butyl (R,Z)-3-(but-3-en-1-yl)-2-oxo-3-(3-oxo-3-phenylprop-1en-1-yl)indoline-1-carboxylate (4ab). 32 mg, yield 74%, yellow oil. 1 H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.0 Hz, 1H), 7.64−7.66 (m, 2H), 7.45 (t, J = 7.6 Hz, 1H), 7.32 (t, J = 7.6 Hz, 2H), 7.16−7.20 (m, 1H), 6.94−7.00 (m, 2H), 6.84 (d, J = 12 Hz, 1H), 6.42 (d, J = 12 Hz, 1H), 5.02 (t, J = 7.6 Hz, 1H), 2.59−2.71 (m, 2H), 1.63−1.64 (m, 12H), 1.47 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 191.0, 175.4, 149.5, 142.4, 140.3, 137.4, 137.3, 132.8, 130.3, 128.4, 128.3, 128.0, e127.5, 123.8, 123.1, 116.5, 114.7, 83.7, 54.2, 39.8, 28.2, 25.9, 18.0. IR (KBr) 2978, 2929, 2846, 1792, 1768, 1726, 1668, 1609, 1579, 1478, 1464, 1448, 1368, 1348, 1295, 1249, 1149, 1005, 845, 751, 688, 464. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C27H30NO4 432.2175; found 432.2172. [α]27.4D = 9.3 (c = 0.8, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 20:80, 254 nm, 1.0 mL/min): major 5.4 min, minor 6.2 min. Enantiomeric excess: 88%. tert-Butyl (S,E)-2-oxo-3-(3-oxo-3-phenylprop-1-en-1-yl)-3-phenylindoline-1-carboxylate (E-4a). 34 mg, yield 82%, white soild, mp 112−114 °C. 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 8.4 Hz, 1H), 7.89−7.91 (m, 2H), 7.54−7.58 (m, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.40−7.43 (m, 1H), 7.35−7.39 (m, 2H), 7.27−7.30 (m, 6H), 7.08 (d, J = 15.6 Hz, 1H), 1.65 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 190.0, 173.6, 149.1, 145.3, 139.4, 138.2, 137.3, 133.2, 129.2, 128.9, 128.8, 128.7, 128.6, 128.2, 127.7, 126.8, 125.6, 125.0, 115.6, 85.0, 59.6, 28.1. IR (KBr) 3057, 2980, 1793, 1668, 1579, 1448, 1369, 1290, 1232, 1148, 1081, 1004, 844, 696, 468, 403. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for C28H25NNaO4 462.1681; found 462.1685. [α]23.5D = −78 (c = 1.0, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 10:90, 254 nm, 1.0 mL/min): major 7.8 min, minor 6.5 min. Enantiomeric excess: 51%. tert-Butyl (S,Z)-3-(3-ethoxy-3-oxoprop-1-en-1-yl)-2-oxo-3-phenylindoline-1-carboxylate (5). 19 mg, yield 46%, yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.0 Hz, 1H), 7.36−7.41 (m, 1H), 7.30−7.32 (m, 3H), 7.18−7.23 (m, 4H),6.62 (d, J = 11.6 Hz, 1H), 6.10 (d, J = 12.0 Hz, 1H), 3.88−3.98 (m, 2H), 1.60 (s, 9H), 1.12 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 173.9, 164.7, 149.7, 145.8, 141.6, 140.8, 130.1, 128.8, 128.7, 128.0, 127.4, 124.6, 124.4, 123.6, 115.2, 84.0, 60.5, 58.5, 28.1, 14.0. IR (KBr) 2981, 2933, 1794, 1765, 1728, 1646, 1603, 1478, 1464, 1448, 1394, 1369, 1343, 1298, 1250, 1149, 1090, 1036, 982, 839, 754, 696. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C24H26NO5 408.1811; found 408.1804. [α]25.2D = −0.6 (c = 0.15, CHCl3) HPLC (Daicel Chiralpak AD-H, iPrOH/Hexane = 10:90, 254 nm, 1.0 mL/min): major 5.2 min, minor 6.8 min. Enantiomeric excess: 44%.

47.8, 28.1. IR (KBr) 3030, 2979, 2929, 1789, 1765, 1726, 1666, 1605, 1494, 1478, 1368, 1292, 1250, 1149, 1005, 735, 699. HRMS (ESITOF) m/z [M + H]+ Calcd for C29H28NO4 454.2018; found 454.2014. [α]25.8D = −25.1 (c = 1.5, CHCl3) HPLC (Daicel Chiralpak AD-H, i-PrOH/Hexane = 20:80, 254 nm, 1.0 mL/min): major 10.5 min, minor 5.7 min. Enantiomeric excess: 90%. tert-Butyl (R,Z)-3-(2-bromobenzyl)-2-oxo-3-(3-oxo-3-phenylprop1-en-1-yl)indoline-1-carboxylate (4u). 45.8 mg, yield 86%, yellow solid, mp 63−65 °C. 1H NMR (400 MHz, CDCl3) δ 7.64 (d, J = 7.2 Hz, 2H), 7.57 (d, J = 8.4 Hz, 1H), 7.44 (t, J = 7.2 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 7.30 (t, J = 7.6 Hz, 2H), 7.08−7.13 (m, 3H), 6.99−7.03 (m, 1H), 6.85−6.91 (m, 3H), 6.61 (d, J = 12 Hz, 1H), 3.63 (d, J = 13.6 Hz, 1H), 3.44 (d, J = 13.6 Hz, 1H), 1.62 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 190.9, 175.0, 149.2, 141.9, 140.3, 137.2, 134.4, 132.9, 131.9, 128.8, 128.7, 128.4, 128.3, 127.7, 126.8, 126.3, 124.5, 123.5, 114.4, 83.7, 55.1, 45.2, 28.2. IR (KBr) 2922, 2859, 1776, 1765, 1726, 1666, 1478, 1467, 1368, 1349, 1301, 1250, 1149, 1005, 749, 428, 411. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C29H27BrNO4 532.1123; found 532.1110. [α]25.8D = −41.6 (c = 0.9, CHCl3) HPLC (Daicel Chiralpak AD-H, i-PrOH/Hexane = 5:95, 254 nm, 1.0 mL/min): major 20.6 min, minor 18.9 min. Enantiomeric excess: 90%. tert-Butyl (R,Z)-3-methyl-2-oxo-3-(3-oxo-3-phenylprop-1-en-1yl)indoline-1-carboxylate (4v). 20.9 mg, yield 60%, white solid, mp 106−108 °C. 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.4 Hz, 1H), 7.67−7.69 (m, 2H), 7.47 (t, J = 7.6 Hz, 1H), 7.34 (t, J = 7.6 Hz, 2H), 7.17−7.21 (m, 1H), 6.99−7.07 (m, 2H), 6.82 (d, J = 12 Hz, 1H), 6.35 (d, J = 12 Hz, 1H), 1.65 (s, 9H), 1.63 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 191.2, 176.2, 149.6, 143.1, 139.7, 137.1, 133.0, 132.1, 128.4, 128.3, 128.1, 127.4, 124.2, 122.6, 115.0, 83.9, 50.0, 28.3, 28.2. IR (KBr) 2980, 2933, 1793, 1769, 1730, 1669, 1606, 1479, 1465, 1449, 1369, 1348, 1294, 1250, 1150, 1006, 843, 753, 737, 689, 463, 402. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C23H24NO4 378.1705; found 378.1698. [α]23.7D = −16.1 (c = 0.6, CHCl3) HPLC (Daicel Chiralpak IC, i-PrOH/Hexane = 20:80, 254 nm, 1.0 mL/min): major 6.8 min, minor 9.0 min. Enantiomeric excess: 89%. tert-Butyl(R,Z)-3-(2-ethoxy-2-oxoethyl)-2-oxo-3-(3-oxo-3-phenylprop-1-en-1-yl)indo-line-1-carboxylate (4w). 36 mg, yield 80%, yellow oil.1H NMR (400 MHz, CDCl3) δ 7.62−7.65 (m, 3H), 7.47 (t, J = 7.6 Hz, 1H), 7.32 (t, J = 7.6 Hz, 2H), 7.09−7.16 (m, 2H), 6.91− 6.95 (m, 1H), 6.68 (d, J = 12 Hz, 1H), 6.35 (d, J = 12 Hz, 1H), 3.93 (q, J = 7.2 Hz, 2H), 3.09 (s, 2H), 1.65 (s, 9H), 1.03 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 192.0, 174.7, 168.8, 149.3, 140.8, 138.7, 136.7, 133.1, 128.9, 128.8, 128.4, 128.3, 128.1, 124.0, 123.9, 114.8, 84.0, 60.9, 52.0, 43.5, 28.2, 13.8. IR (KBr) 3054, 2980, 2933, 1794, 1768, 1730, 1670, 1605, 1479, 1465, 1393, 1348, 1294, 1250, 1150, 1089, 1006, 842, 752, 689, 402. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C26H28NO6 450.1917; found 450.1914. [α]25.0D = −23.3 (c = 0.48, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 20:80, 254 nm, 1.0 mL/min): major 16.3 min, minor 21.5 min. Enantiomeric excess: 89%. tert-Butyl (R,Z)-2-oxo-3-(3-oxo-3-phenylprop-1-en-1-yl)-3-(prop2-yn-1-yl)indo-line-1-carboxylate (4x). 31.2 mg, yield 78%, yellow oil. 1 H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 7.2 Hz, 2H), 7.47 (t, J = 7.6 Hz, 1H), 7.34 (t, J = 7.6 Hz, 2H), 7.22− 7.26 (m, 2H), 7.00 (t, J = 7.6 Hz, 1H), 6.94 (d, J = 12 Hz, 1H), 6.61 (d, J = 12 Hz, 1H), 2.96 (dd, J = 2.4 Hz, 16.4 Hz, 1H), 2.62 (dd, J = 2.4 Hz, 16.4 Hz, 1H), 2.10 (t, J = 2.4 Hz, 1H), 1.65 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 190.4, 174.3, 149.3, 141.2, 140.3, 137.0, 133.0, 129.2, 128.6, 128.4, 128.3, 127.7, 124.0, 123.4, 114.8, 84.0, 78.5, 72.2, 52.4, 30.9, 28.1. IR (KBr) 3287, 2980, 2930, 1793, 1766, 1727, 1666, 1605, 1478, 1465, 1449, 1392, 1369, 1347, 1293, 1251, 1150, 1006, 752, 736, 688, 403. HRMS (ESI-TOF) m/z [M + Na]+ Calcd for C25H23NNaO4 424.1525, found 424.1504. [α]25.9D = 36.3 (c = 0.55, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 20:80, 254 nm, 1.0 mL/min): major 8.9 min, minor 11.6 min. Enantiomeric excess: 87%. tert-Butyl (R,Z)-3-allyl-2-oxo-3-(3-oxo-3-phenylprop-1-en-1-yl)indoline-1-carboxylate (4y). 31.8 mg, yield 79%, white solid, mp 160−162 °C. 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 7.2 Hz, 2H), 7.45 (t, J = 7.6 Hz, 1H), 7.32 (t, J = 7.6 Hz, 4848

DOI: 10.1021/acs.joc.7b00571 J. Org. Chem. 2017, 82, 4840−4850

Article

The Journal of Organic Chemistry Procedure for the Preparation of Product E-5c and E-5w. To a solution of 4 (0.1 mmol) in CH2Cl2 (5 mL) was added CF3CO2H (10 mmol, 10.0 equiv) at 0 °C. The reaction mixture was allowed to warm up to room temperature and stirred for 2 h. Saturated Na2CO3 aqueous solution (10 mL) was added to quench the reaction, and the resulting mixture was extracted with CH2Cl2 (10 mL × 3) and the combined organic layers were washed with brine (20 mL). After drying over Na2SO4, the solvent was removed and the crude product was purified by flash column chromatography (hexane/acetone = 1/1) to give product E-5. (S,E)-5-Methyl-3-(3-oxo-3-phenylprop-1-en-1-yl)-3-phenylindolin-2-one (E-5c). 30.8 mg, yield 87%, white solid, mp 48−49 °C. 1H NMR (400 MHz, CDCl3) δ 8.6 (s, 1H), 7.82−7.84 (m, 2H), 7.47 (t, J = 7.2 Hz, 1H), 7.36 (t, J = 7.2 Hz, 2H), 7.18−7.30 (m, 6H), 7.05 (d, J = 15.2 Hz, 1H), 6.98−7.02 (m, 2H), 6.81 (d, J = 8.0 Hz, 1H), 2.26 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 190.4, 177.8, 145.5, 138.4, 137.9, 137.5, 133.1, 133.0, 131.0, 129.4, 128.9, 128.7, 128.6, 128.0, 127.5, 126.7, 126.4, 110.4, 60.1, 21.2. IR (KBr) 3256, 3058, 2921, 2863, 1710, 1671, 1612, 1492, 1446, 1287, 1213, 1017, 812, 748, 695, 409. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C24H20NO2 354.1494; found 354.1486. [α]26.3D = −25.1 (c = 1.0, CHCl3) HPLC (Daicel Chiralpak IB, i-PrOH/Hexane = 30:70, 254 nm, 0.7 mL/min): major 6.7 min, minor 7.4 min. Enantiomeric excess: 82%. Ethyl (R,E)-2-(2-oxo-3-(3-oxo-3-phenylprop-1-en-1-yl)indolin-3yl)acetate (E-5w). 31.5 mg, yield 90%, white solid, mp 123−125 °C. 1H NMR (400 MHz, CDCl3) δ 9.27 (s, 1H), 7.86 (d, J = 7.2 Hz, 2H), 7.53−7.56 (m, 1H), 7.41−7.45 (m, 2H), 7.26−7.32 (m, 2H), 7.05−7.12 (m, 2H), 7.00 (d, J = 7.2 Hz, 1H), 6.93 (m, J = 15.6 Hz, 1H), 3.97 (dd, J = 4.0 Hz, J = 7.2 Hz, 2H), 3.30 (d, J = 8.0 Hz, 1H), 3.13 (d, J = 8.0 Hz, 1H), 1.05 (t, J = 6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 190.2, 178.3, 169.1, 145.2, 141.4, 137.4, 133.1, 129.5, 129.1, 128.7, 128.6, 126.1, 124.1, 122.8, 110.6, 61.0, 53.0, 40.2, 13.8. IR (KBr) 3268, 3062, 2981, 1730, 1671, 1616, 1578, 1484, 1471, 1446, 1371, 1292, 1196, 1014, 754, 694, 490. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C21H20NO4 350.1392; found 350.1388. [α]23.8D = 5.9 (c = 2.5, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 20:80, 254 nm, 1.0 mL/min): major 26.1 min, minor 39.2 min. Enantiomeric excess: 88%. Procedure for the Preparation of Product 6w. To a solution of E-5w (0.1 mmol) in ethyl acetate (5 mL) was added Pd/C (0.5 mmol, 5.0 equiv). The reaction mixture was stirred under hydrogen atmosphere for 8 h at room temperature. The reaction mixture was passed through Celite to remove Pd/C, and the residue was washed with ether. After the removal of solvent, the crude product was purified by flash column chromatography (hexane/ethyl acetate = 4/1) to give 6w. Ethyl (S)-2-(2-oxo-3-(3-phenylpropyl)indolin-3-yl)acetate (6w). 25.3 mg, yield 75%, white solid, mp 76−77 °C. 1H NMR (400 MHz, CDCl3) δ 8.69 (s, 1H), 7.08−7.15 (m, 3H), 7.02−7.07 (m, 2H), 6.90−6.96 (m, 3H), 6.80 (d, J = 12.0 Hz, 1H), 3.73−3.84 (m, 2H), 2.93 (d, J = 16.0 Hz, 1H), 2.74 (d, J = 16.0 Hz, 1H), 2.34−2.46 (m, 2H), 1.82 (dt, J = 4.0 Hz, J = 12.8 Hz, 1H), 1.71 (dt, J = 4.0 Hz, J = 12.8 Hz, 1H), 1.39−1.44 (m, 1H), 1.11−1.18 (m, 1H), 0.89 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 180.5, 168.7, 140.5, 130.4, 127.3, 127.2, 127.1, 124.8, 121.9, 121.3, 108.8, 59.5, 49.3, 40.4, 36.8, 34.7, 24.2, 12.7. IR (KBr) 3245, 2937, 2859, 1732, 1620, 1471, 1456, 1372, 1339, 1298, 1264, 1186, 1029, 748, 699, 664, 486. HRMS (ESITOF) m/z [M + H]+ Calcd for C21H24NO3 338.1756; found 338.1751. [α]27.5D = −4.4 (c = 0.25, CHCl3) HPLC (Daicel Chiralpak PC-II, i-PrOH/Hexane = 20:80, 254 nm, 1.0 mL/min): major 18.2 min, minor 21.7 min. Enantiomeric excess: 89%. Procedure for the Preparation of Product 7. A solution of 4u (0.2 mmol), Pd(OAc)2 (0.02 mmol, 0.1 equiv) and PPh3 (0.04 mmol, 0.2 equiv) in 2 mL of Et3N was stirred at 90 °C under N2 atomsphere. The reaction mixture was stirred for 8 h until completion as monitored by TLC. The reaction mixture was diluted with ethyl acetate, and then quenched with saturated aqueous NH4Cl. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with water and brine, then dried over Na2SO4 and evaporated to give the crude product, which was dissolved in CH3CN (3 mL) and

H2O(2 mL). RuCl3 (0.007 mmol, 0.035 equiv), Oxone (0.3 mmol, 1.5 equiv) and NaHCO3 (0.9 mmol, 4.5 equiv) were added to this solution and the resulting mixture was stirred at room temperature for 8 h. The reaction mixture was diluted with ethyl acetate, and then quenched with saturated aqueous NH4Cl. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with water and brine. After dried over Na2SO4 and evaporated, the crude product was purified by flash column chromatography (hexane/ethyl acetate = 8/1) to give 7 in 42% yield for two steps. tert-Butyl (S)-1,2′-dioxo-1,3-dihydrospiro[indene-2,3′-indoline]1′-carboxylate 7. 29.4 mg, yield for two steps 42%, white solid, mp 73−74 °C. 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 8.0 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.71 (t, J = 7.6 Hz, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.34 (t, J = 8.0 Hz, 1H), 7.10 (t, J = 7.6 Hz, 1H), 6.91 (d, J = 7.2 Hz, 1H), 3.87 (d, J = 17.2 Hz, 1H), 3.46 (d, J = 17.2 Hz, 1H), 1.64 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 198.8, 173.2, 148.9, 140.9, 135.9, 134.5, 129.1, 128.8, 128.4, 126.5, 125.7, 124.9, 121.9, 115.6, 84.7, 63.6, 38.7, 28.1. IR (KBr) 2980, 2931, 1791, 1766, 1719, 1605, 1478, 1464, 1370, 1345, 1289, 1251, 1149, 1085, 1005, 892, 873, 839, 705, 497. HRMS (ESI-TOF) m/z [M + H]+ Calcd for C21H20NO4 350.1392; found 350.1389. [α]25.8D = −93.8 (c = 0.05, CHCl3) HPLC (Daicel Chiralpak AD-H, i-PrOH/Hexane = 10:90, 254 nm, 1.0 mL/min): major 12.0 min, minor 6.9 min. Enantiomeric excess: 89%.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b00571. Crystal data for 3h (CIF) 1 H and 13C NMR spectra and HPLC traces (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. Fax: 0086-21-64166128. Tel: 0086-21-54925182. *E-mail: [email protected] ORCID

Gang Zhao: 0000-0003-2601-9124 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Financial support from Chinese Academy of Sciences (XDB 20020100) and the National Natural Science Foundation of China (Nos. 21272247, 21572247, 21290184) is gratefully acknowledged.

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REFERENCES

(1) For recent reviews, see: (a) Corey, E. J.; Guzman-Perez, A. Angew. Chem., Int. Ed. 1998, 37, 388. (b) Christoffers, J.; Baro, A. Angew. Chem., Int. Ed. 2003, 42, 1688. (c) Douglas, C. J.; Overman, L. E. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 5363. (d) Cozzi, P. G.; Hilgraf, R.; Zimmermann, N. Eur. J. Org. Chem. 2007, 2007, 5969. (e) Shibasaki, M.; Kanai, M. Chem. Rev. 2008, 108, 2853. (f) Shibasaki, M.; Kanai, M.; Matsunaga, S.; Kumagai, N. Acc. Chem. Res. 2009, 42, 1117. (g) Quasdorf, K. W.; Overman, L. E. Nature 2014, 516, 181. (2) (a) Sibi, M.; Manyem, P. S. Tetrahedron 2000, 56, 8033. (b) Krause, N.; Hoffmann-Roder, A. Synthesis 2001, 2001, 171. (c) Hanashima, Y.; Hotta, D.; Sodeoka, M. J. Am. Chem. Soc. 2002, 124, 11240. (d) Harada, S.; Kumagai, N.; Kinoshita, T.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc. 2003, 125, 2582. (e) Christoffers, J.; Baro, A. Angew. Chem., Int. Ed. 2003, 42, 1688. (f) Christoffers, J. Chem. - Eur. J. 2003, 9, 4862.

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DOI: 10.1021/acs.joc.7b00571 J. Org. Chem. 2017, 82, 4840−4850

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The Journal of Organic Chemistry (3) (a) Bella, M.; Jørgensen, K. A. J. Am. Chem. Soc. 2004, 126, 5672. (b) Wang, X.; Kitamura, M.; Maruoka, K. J. Am. Chem. Soc. 2007, 129, 1038. (c) Lan, Q.; Wang, X.; Maruoka, K. Tetrahedron Lett. 2007, 48, 4675. (d) Chen, Z.; Furutachi, M.; Kato, Y.; Matsunaga, S.; Shibasaki, M. Angew. Chem., Int. Ed. 2009, 48, 2218. (4) (a) Hasegawa, Y.; Gridnev, I. D.; Ikariya, T. Angew. Chem., Int. Ed. 2010, 49, 8157. (b) Misaki, T.; Kawano, K.; Sugimura, T. J. Am. Chem. Soc. 2011, 133, 5695. (c) Wang, Z.; Chen, Z. L.; Bai, S.; Li, W.; Liu, X. H.; Lin, L. L.; Feng, X. M. Angew. Chem., Int. Ed. 2012, 51, 2776. (5) Kang, G. W.; Wu, Q. Q.; Liu, M. C.; Xu, Q. F.; Chen, Z. Y.; Chen, W. L.; Luo, Y. Q.; Ye, W.; Jiang, J.; Wu, H. Y. Adv. Synth. Catal. 2013, 355, 315. (6) Wang, Z.; Zhang, Z. L.; Yao, Q.; Liu, X. H.; Cai, Y. F.; Lin, L. L.; Feng, X. M. Chem. - Eur. J. 2013, 19, 8591. (7) Poulsen, T. B.; Bernardi, L.; Bell, M.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2006, 45, 6551. (8) (a) Chai, Z.; Zhao, G. Catal. Sci. Technol. 2012, 2, 29. (b) Cao, D. D.; Chai, Z.; Zhang, J. X.; Ye, Z. Q.; Xiao, H.; Wang, H. Y.; Zhao, G. Chem. Commun. 2013, 49, 5972. (c) Wang, H. Y.; Chai, Z.; Zhao, G. Tetrahedron 2013, 69, 5104. (d) Wang, H. Y.; Zhang, J. X.; Cao, D. D.; Zhao, G. ACS Catal. 2013, 3, 2218. (e) Cao, D. D.; Zhang, J. X.; Wang, H. Y.; Zhao, G. Chem. - Eur. J. 2015, 21, 9998. (f) Lu, Y. P.; Cao, D. D.; Zhang, J. X.; Wang, H. Y.; Zou, G.; Zhao, G. Tetrahedron 2016, 72, 4141. (g) Zhang, J. X.; Wang, H. Y.; Jin, Q. W.; Zheng, C. W.; Shang, Y. J.; Zhao, G. Org. Lett. 2016, 18, 4774. (h) Zhang, J. X.; Cao, D. D.; Wang, H. Y.; Zheng, C. W.; Shang, Y. J.; Zhao, G. J. Org. Chem. 2016, 81, 10558. (9) (a) Kagamizono, T.; Sskai, N.; Arai, K.; Kobinata, K.; Osada, H. Tetrahedron Lett. 1997, 38, 1223. (b) Lin, Z. J.; Zhu, T. J.; Fang, Y. C.; Gu, Q. Q. Magn. Reson. Chem. 2008, 46, 1212. (10) (a) Modena, G. Acc. Chem. Res. 1971, 4, 73. (b) Apeloig, Y.; Rappoport, Z. J. Am. Chem. Soc. 1979, 101, 5095. (11) (a) Duan, S. W.; Jing, A.; Chen, J. R.; Xiao, W. J. Org. Lett. 2011, 13, 2290. (b) Li, X.; Li, Y. M.; Peng, F. Z.; Wu, S. T.; Li, Z. Q.; Sun, Z. W.; Zhang, H. B.; Shao, Z. H. Org. Lett. 2011, 13, 6160. (c) Wang, T. L.; Yao, W. J.; Zhong, F. R.; Pang, G. H.; Lu, Y. X. Angew. Chem., Int. Ed. 2014, 53, 2964. (d) De, S.; Das, M. K.; Bhunia, S.; Bisai, A. Org. Lett. 2015, 17, 5922. (e) Jin, Q. W.; Chai, Z.; Huang, Y. M.; Zou, G.; Zhao, G. Beilstein J. Org. Chem. 2016, 12, 725. (12) Ma, S. M.; Lu, X. Y.; Li, Z. G. J. Org. Chem. 1992, 57, 709.

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DOI: 10.1021/acs.joc.7b00571 J. Org. Chem. 2017, 82, 4840−4850