Annulation of Acrylamides with Aliphatic Acyl

Apr 17, 2017 - Radical Decarboxylation/Annulation of Acrylamides with Aliphatic Acyl Peroxides. Changduo Pan†, Yu Fu†, Qingting Ni†, and Jin-Tao...
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Radical Decarboxylation/Annulation of Acrylamides with Aliphatic Acyl Peroxides Changduo Pan,*,† Yu Fu,† Qingting Ni,† and Jin-Tao Yu*,‡ †

School of Chemical and Environmental Engineering, Jiangsu University of Technology, Changzhou 213001, P.R. China School of Petrochemical Engineering, Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, Changzhou University, Changzhou 213164, P.R. China

‡

S Supporting Information *

ABSTRACT: A radical decarboxylation/annulation of acrylamides with aliphatic acyl peroxides was developed, giving a series of linear alkylated oxindoles in moderate to good yields. The reaction used aliphatic acyl peroxides as the linear alkyl radical source and tolerated a broad scope of substrates under metal-free conditions, offering a simple and efficient approach toward alkylated oxindoles.

T

To date, the most efficient example in the construction of linear alkylated oxindoles was the decarboxylation/C−H functionalization promoted by visible light in the presence of PhI(OAc)2 developed by Zhu using aliphatic acids as linear alkyl radical precursors (eq 2, Scheme 1).7 However, searching for more efficient and convenient approaches to provide linear alkyl radicals from readily available sources is still highly desired in the construction of alkylated oxindoles. Diacyl peroxides, which can be simply prepared from acyl chlorides or carboxylic acids under the oxidation of H2O2,8,9g are mostly used as radical initiators in organic reactions. Recently, diacylperoxides were employed as favorable aryl/alkyl radical precursors to construct carbon−carbon bonds through homolytic O−O bond cleavage followed by CO2 extrusion.9 No doubt, linear alkyl radical could be formed by the homolysis of the corresponding aliphatic diacylperoxides. Herein, we report an efficient approach involving the metal-free decarboxylation/ annulation of acrylamides using aliphatic diacylperoxides as a linear alkyl source to access alkylated oxindoles (eq 3, Scheme 1). Initially, the reaction of N-methyl-N-phenylmethacrylamide (1a) with lauroyl peroxide (LPO, 2a) was conducted to optimize the reaction conditions. Gratifyingly, the desired product 3aa was isolated in 33% yield when DCE was used as the solvent (Table 1, entry 1). Subsequently, other solvents such as DCM, PhCl, PhF, PhCF3, PhH, acetone, and CH3CN were investigated. The results showed that PhH performed with the best efficiency, giving the product 3aa in 81% yield (Table 1, entry 6). Temperature control experiments were also conducted. The yield of 3aa dropped obviously at a lower temperature (85 °C), whereas no better yield resulted at elevated temperature (120 °C) (Table 1, entry 6). With the optimized conditions in hand, the scope of acrylamides was investigated at first. As shown in Figure 1,

he oxidative cross-coupling concerning C−H functionalization has evolved to be one of the most powerful and efficient methods for the establishment of carbon−carbon bonds due to its inherent atom economy and eco-friendly nature.1 Recently, radical oxidative cross-coupling has been demonstrated as a distinctive choice in the construction of complex organic molecules.2 For instance, this strategy has been successfully utilized in the cascade difunctionalization/ annulation of acrylamides to synthesize functionalized oxindoles,3 which widely exist in natural products and pharmaceutical compounds.4 Particularly, the construction of alkylated oxindoles has been investigated by many groups indepth. For example, by activing the inert C(sp3)−H bonds as the radical sponsor, the difunctionalization/annulation of acrylamides were realized, leading to a series of alkylated oxindoles.5 However, they mainly dealt with branched alkyl radicals and suffered from regioisomers when linear alkyl radicals were concerned. For the synthesis of linear alkylated oxindoles, aliphatic aldehydes were developed as alkyl radical precursors (eq 1, Scheme 1).6 Nevertheless, the yields were not satisfactory in the case of α-unsubstituted aliphatic aldehydes, due to the relatively low stability of the primary carbon radical. Scheme 1. Alkylarylation of Acrylamides Using Linear Alkyl Radical Precursors

Received: March 21, 2017 Published: April 17, 2017 © 2017 American Chemical Society

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DOI: 10.1021/acs.joc.7b00663 J. Org. Chem. 2017, 82, 5005−5010

Note

The Journal of Organic Chemistry Table 1. Screening the Optimized Reaction Conditionsa

entry

solvent

yield (%)

1 2 3 4 5 6 7 8

DCE DCM PhCl PhF PhCF3 PhH acetone CH3CN

33 25 51 63 66 81 (68,b 80c) 21 16

atom offered better yield than those with alkyl (Figure 1, 3na). Acrylamide substrate prepared from tetrahydroisoquinoline (1p) was also tested and gave the corresponding tricyclic oxindole in 73% yield (Figure 1, 3pa). Next, the scope of alkyl acyl peroxides was explored. As shown in Figure 2, propionic peroxyanhydride (2b), butyric peroxyanhydride (2c), pentanoic peroxyanhydride (2d), hexanoic peroxyanhydride (2e), heptanoic peroxyanhydride (2f), octanoic peroxyanhydride (2g), nonanoic peroxyanhydride (2h), decanoic peroxyanhydride (2i), tetradecanoic peroxyanhydride (2j), palmitic peroxyanhydride (2k), and 3phenylpropanoic peroxyanhydride (2l) all reacted smoothly with N-methyl-N-phenylmethacrylamide (1a) to provide the desired alkylated oxindoles in good yields. However, a trace amount of product along with considerable diphenyl was observed when benzoyl peroxide (2m) was employed. To investigate the reaction mechanism, 2,2,6,6-tetramethylpiperidine oxide (TEMPO) was added into the reaction as a radical inhibitor. As expected, no product was detected and the adduct formed by TEMPO and an undecyl radical was detected by GCMS (Scheme 2). These results suggested this transformation might undergo a radical pathway, and the alkyl radical is the possible intermediate. According to these results and previous reported works, the plausible mechanism is proposed in Scheme 3. Initially, peroxide 2 is thermally decomposed. The following CO2 extrusion generates the alkyl radical A, which adds to the double bond of acrylamide (1) to give radical intermediate B. Then, radical B undergoes intramolecular cyclization to

a

Reaction conditions: 1a (0.2 mmol) and 2a (0.4 mmol) in solvent (2 mL) at 100 °C under N2 for 12 h. b85 °C. c120 °C.

acrylamides with either an electron-withdrawing or -donating substituent, such as methyl, isopropyl, methoxyl, halogen, benzyl, trifluoromethyl, or ester group, all reacted well with lauroyl peroxide, giving the desired products in moderate to good yields. Specially, acrylamides with ortho-substituents gave relatively lower yields due to the steric hindrance (Figure 1, 3ca and 3da). To examine the regioselectivity, reaction of acrylamides bearing a meta-substituent (1e and 1f) was conducted, resulting in two regioisomers in ratios of 1.7:1 and 1.8:1, respectively. Acrylamide bearing a phenyl on the N

Figure 1. Scope of the acrylamides. Reaction conditions: 1 (0.2 mmol) and 2a (0.4 mmol, 2 equiv) in PhH (2 mL) at 100 °C under N2 for 12 h. The ratio of the isomers was determined by 1H NMR. 5006

DOI: 10.1021/acs.joc.7b00663 J. Org. Chem. 2017, 82, 5005−5010

The Journal of Organic Chemistry

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Note

EXPERIMENTAL SECTION

General Information. All chemicals were used as received without further purification unless stated otherwise. NMR spectra were recorded at ambient temperature on a 400 MHz NMR spectrometer. Chemical shifts (δ) are given in parts per million relative to TMS, and the coupling constants, J, are given in hertz. HRMS data were recorded on a TOF LC/MS equipped with electrospray ionization (ESI) probe operating in positive or negative ion mode. LPO (2a) is commercially available. Other aliphatic diacylperoxides were prepared according to the literature.8,9g Experimental General Procedure. Under N2, the mixture of acrylamides 1 (0.2 mmol), aliphatic diacylperoxide 2 (0.4 mmol), and PhH (2 mL) was added into the tube and sealed. The reaction mixture was vigorously stirred at 100 °C for 12 h. Then, the solvent was evaporated under reduced pressure, and the residue was purified by flash column chromatography on silica gel to afford the products. 3-Dodecyl-1,3-dimethylindolin-2-one (3aa). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (53.3 mg, 81%): 1H NMR (CDCl3, 400 MHz) δ 7.28− 7.23 (m, 1H), 7.17−7.15 (m, 7H), 7.08−7.04 (m, 1H), 6.83 (d, J = 7.7 Hz, 1H), 3.21 (s, 3H), 1.92−1.84 (m, 1H), 1.75−1.67 (m, 1H), 1.34 (s, 3H), 1.29−1.13 (m, 18H), 1.02−0.79 (m, 5H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.9, 143.3, 134.4, 127.5, 122.5, 122.4, 107.8, 48.4, 38,5, 31.9, 29.8, 29.6, 29.57, 29.56, 29.34, 29.32, 26.1, 24.5, 23.8, 22.7, 14.1; HRMS (ESI) m/z calcd for C22H36NO (M + H)+ 330.2791, found 330.2793. 3-Dodecyl-1,3,5-trimethylindolin-2-one (3ba). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (56.2 mg, 82%): 1H NMR (CDCl3, 400 MHz) δ 7.05 (d, J = 7.8 Hz, 1H), 6.98 (s, 1H), 6.72 (d, J = 7.8 Hz, 1H), 3.18 (s, 3H), 2.35 (s, 3H), 1.89−1.82 (m, 1H), 1.73−1.65 (m, 1H), 1.32 (s, 3H), 1.29−1.14 (m, 18H), 0.99−0.82 (m, 5H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.8, 140.9, 134.4, 131.8, 127.7, 123.3, 107.5, 48.5, 38.6, 31.9, 29.8, 29.6, 29.5, 29.3, 26.1, 24.5, 23.8, 22.7, 21.2, 14.1; HRMS (ESI) m/z calcd for C23H38NO (M + H)+ 344.2948, found 344.2949. 3-Dodecyl-1,3,7-trimethylindolin-2-one (3ca). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (50.7 mg, 74%): 1H NMR (CDCl3, 400 MHz) δ 6.99− 6.91 (m, 3H), 3.49 (s, 3H), 2.58 (s, 3H), 1.91−1.83 (m, 1H), 1.71− 1.63 (m, 1H), 1.31 (s, 3H), 1.29−1.14 (m, 18H), 1.00−0.76 (m, 5H); 13 C{1H} NMR (CDCl3, 100 MHz) δ 180.6, 141.1, 135.0, 131.3, 122.3, 120.4, 119.4, 47.7, 38.8, 31.9, 29.8, 29.6, 29.5, 29.4, 29.35, 29.33, 24.5, 24.3, 22.7, 19.1, 14.1; HRMS (ESI) m/z calcd for C23H38NO (M + H)+ 344.2948, found 344.2949. 3-Dodecyl-1,3,5,7-tetramethylindolin-2-one (3da). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (50.7 mg, 71%): 1H NMR (CDCl3, 400 MHz) δ 6.79−6.78 (m, 2H), 3.46 (s, 3H), 2.53 (s, 3H), 2.29 (s, 3H), 1.89− 1.81 (m, 1H), 1.68−1.60 (m, 1H), 1.29 (s, 3H), 1.27−1.14 (m, 18H), 0.99−0.76 (t, J = 6.8 Hz, 5H); 13C{1H} NMR (CDCl3, 100 MHz) δ 181.5, 138.6, 135.1, 131.7, 131.6, 121.1, 119.1, 47.8, 38.9, 31.9, 29.8, 29.63, 29.60, 29.4, 29.3, 24.5, 24.3, 22.7, 20.8, 18.9, 14.1; HRMS (ESI) m/z calcd for C24H40NO (M + H)+ 358.3104, found 358.3108. 3-Dodecyl-1,3,6-trimethylindolin-2-one and 3-Dodecyl-1,3,4-trimethylindolin-2-one (3ea and 3ea′). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (53.5 mg, 78%): 1H NMR (CDCl3, 400 MHz) δ 7.18−7.14 (m, 0.6H), 7.05−7.03 (m, 0.36H), 6.88−6.86 (m, 0.35H), 6.83−6.81 (m, 0.59H), 6.69−6.66 (m, 1H), 3.19 (d, 3H), 2.39 (s, 1.12H), 2.35 (s, 1.89H), 1.98−1.93 (m, 1H), 1.89−1.81 (m, 0.38H), 1.73−1.65 (m, 0.63H), 1.41 (s, 1.94H), 1.32 (s, 1.15H), 1.31−1.13 (m, 18H), 0.89−0.63 (m, 5H); 13C{1H} NMR (CDCl3, 100 MHz) δ 181.2, 180.9, 143.6, 143.4, 137.6, 134.1, 131.4, 130.8, 127.4, 124.9, 122.8, 122.2, 108.8, 105.6, 49.6, 48.2, 38.5, 36.4, 31.9, 29.8, 29.7, 29.6, 29.5, 29.34, 29.31, 26.2, 26.0, 24.9, 24.5, 23.9, 22.7, 22.4, 21.8, 18.1, 14.1; MS (EI) 343, 188, 175. 3-Dodecyl-6-methoxy-1,3-dimethylindolin-2-one and 3-Dodecyl4-methoxy-1,3-dimethylindolin-2-one (3fa and 3fa′). Flash column

Figure 2. Scope of acyl peroxides. Reaction conditions: 1a (0.2 mmol) and 2 (0.4 mmol) in PhH (2 mL) at 100 °C under N2 for 12 h.

Scheme 2. Mechanism Study

Scheme 3. Proposed Mechanism

produce radical intermediate C, which is oxidized by peroxide 2 to produce cation intermediate D. Finally, product 3 is generated by deprotonation of intermediate D. In conclusion, we have developed a metal-free radical decarboxylation/annulation of acrylamides with aliphatic acyl peroxides. Through the procedure, a series of linear alkylated oxindoles were obtained in moderate to good yields. It offers an alternative approach to the convenient and efficient generation of quaternary oxindoles using aliphatic acyl peroxides as a linear alkyl radical source. 5007

DOI: 10.1021/acs.joc.7b00663 J. Org. Chem. 2017, 82, 5005−5010

Note

The Journal of Organic Chemistry

NMR (CDCl3, 100 MHz) δ 181.9, 140.2, 139.2, 135.4, 130.6, 129.9, 127.8, 127.5, 125.3, 121.7, 121.5, 47.7, 38.9, 31.9, 30.1, 29.8, 29.64, 29.60, 29.3, 24.4, 24.1, 22.7, 14.1; HRMS (ESI) m/z calcd for C28H40NO (M + H)+ 406.3104, found 406.3106. 3-Dodecyl-1-ethyl-3-methylindolin-2-one (3ma). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (51.4 mg, 75%): 1H NMR (CDCl3, 400 MHz) δ 7.27−7.22 (m, 1H), 7.17−7.15 (m, 1H), 7.07−7.02 (m, 1H), 6.85 (d, J = 7.8 Hz, 1H), 3.85−3.78 (m, 1H), 3.75−3.66 (m, 1H), 1.92−1.84 (m, 1H), 1.74−1.67 (m, 1H), 1.33 (s, 3H), 1.27−1.13 (m, 21H), 1.00− 0.77 (m, 5H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.4, 142.4, 134.6, 127.5, 122.6, 122.1, 107.9, 48.3, 38.6, 34.4, 31.9, 29.7, 29.6, 29.57, 29.53, 29.34, 29.32, 24.4, 23.8, 22.7, 14.1, 12.7; HRMS (ESI) m/z calcd for C23H38NO (M + H)+ 344.2948, found 344.2949. 3-Dodecyl-3-methyl-1-phenylindolin-2-one (3na). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (67.2 mg, 86%): 1H NMR (CDCl3, 400 MHz) δ 7.53−7.49 (m, 2H), 7.41−7.37 (m, 3H), 7.25−7.16 (m, 2H), 7.11− 7.07 (m, 1H), 6.83 (d, J = 7.7 Hz, 1H), 2.03−1.96 (m, 1H), 1.84−1.76 (m, 1H), 1.46 (s, 3H), 1.29−1.17 (m, 18H), 0.98−0.77 (m, 5H); 13 C{1H} NMR (CDCl3, 100 MHz) δ 180.3, 143.3, 134.7, 134.1, 129.5, 127.9, 127.5, 126.6, 122.9, 122.8, 109.2, 48.5, 39.1, 31.9, 29.7, 29.6, 29.58, 29.56, 29.3, 24.5, 24.1, 22.7, 14.1; HRMS (ESI) m/z calcd for C27H38NO (M + H)+ 392.2948, found 392.2951. 1-Benzyl-3-dodecyl-3-methylindolin-2-one (3oa). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (62.4 mg, 77%): 1H NMR (CDCl3, 400 MHz) δ 7.32−7.22 (m, 5H), 7.17−7.11 (m, 2H), 7.04−7.00 (m, 1H), 6.71 (d, J = 7.7 Hz, 1H), 5.00−4.82 (q, 2H), 1.99−1.91 (m, 1H), 1.80−1.72 (m, 1H), 1.40 (s, 3H), 1.31−0.99 (m, 19H), 0.89−0.78 (m, 4H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.9, 142.4, 136.2, 134.3, 128.7, 127.5, 127.4, 127.3, 122.5, 122.4, 108.9, 48.5, 43.6, 38.6, 31.9, 29.7, 29.63, 29.60, 29.5, 29.3, 24.7, 24.2, 22.7, 14.1; HRMS (ESI) m/z calcd for C28H40NO (M + H)+ 406.3104, found 406.3108. 1-Dodecyl-1-methyl-5,6-dihydro-1H-pyrrolo[3,2,1-ij]quinolin2(4H)-one (3pa). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (51.8 mg, 69%): 1H NMR (CDCl3, 400 MHz) δ 7.01−6.99 (m, 2H), 6.96−6.92 (m, 1H), 3.71 (t, J = 5.8 Hz, 2H), 2.79 (t, J = 5.9 Hz, 2H), 2.03−1.97 (m, 2H), 1.88−1.81 (m, 1H), 1.75−1.68 (m, 1H), 1.34 (s, 3H), 1.30− 1.15 (m, 18H), 1.06−0.99 (m, 1H), 0.93−0.80 (m, 4H); 13C{1H} NMR (CDCl3, 100 MHz) δ 179.8, 139.1, 132.9, 126.4, 121.8, 120.4, 119.9, 49.8, 38.7, 38.3, 31.9, 29.8, 29.6, 29.5, 29.3, 24.7, 24.5, 23.4, 22.7, 21.3, 14.1; HRMS (ESI) m/z calcd for C24H38NO (M + H)+ 356.2948, found 356.2949. 3-Benzyl-3-dodecyl-1-methylindolin-2-one (3qa). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (60.7 mg, 75%): 1H NMR (CDCl3, 400 MHz) δ 7.19−7.11 (m, 2H), 7.05−6.98 (m, 4H), 6.82−6.79 (m, 2H), 6.57 (t, J = 7.7 Hz, 1H), 3.11 (d, J = 12.9 Hz, 2H), 2.99 (d, J = 12.9 Hz, 2H), 2.95 (s, 3H), 2.09−2.01 (m, 1H), 1.89−1.81 (m, 1H), 1.29−1.14 (m, 18H), 1.02−0.75 (m, 5H); 13C{1H} NMR (CDCl3, 100 MHz) δ 179.3, 143.9, 136.0, 131.4, 129.8, 127.6, 127.4, 126.3, 123.4, 121.9, 107.6, 54.8, 44.4, 37.1, 31.9, 29.8, 29.63, 29.62, 29.5, 29.35, 29.34, 25.7, 24.4, 22.7, 14.1; HRMS (ESI) m/z calcd for C28H40NO (M + H)+ 406.3104, found 406.3107. 1,3-Dimethyl-3-propylindolin-2-one (3ab).10 Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (28.8 mg, 71%): 1H NMR (CDCl3, 400 MHz) δ 7.29− 7.24 (m, 1H), 7.19−7.16 (m, 1H), 7.09−7.05 (m, 1H), 6.84 (d, J = 7.8 Hz, 1H), 3.21 (s, 3H), 1.92−1.84 (m, 1H), 1.75−1.67 (m, 1H), 1.36 (s, 3H), 1.06−1.92 (m, 1H), 0.89−0.82 (m, 1H), 0.78 (t, J = 7.0 Hz, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.9, 143.3, 134.3, 127.6, 122.5, 122.4, 107.8, 48.5, 40.8, 26.1, 23.7, 17.8, 14.1. 3-Butyl-1,3-dimethylindolin-2-one (3ac).10 Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (32.1 mg, 74%): 1H NMR (CDCl3, 400 MHz) δ 7.28− 7.24 (m, 1H), 7.16−7.15 (m, 1H), 7.08−7.04 (m, 1H), 6.84 (d, J = 7.8 Hz, 1H), 3.21 (s, 3H), 1.92−1.85 (m, 1H), 1.76−1.68 (m, 1H), 1.34 (s, 3H), 1.22−1.13 (m, 2H), 1.00−0.91 (m, 2H), 0.77 (t, J = 7.3 Hz,

chromatography on silica gel (petroleum ether/ethyl acetate 5/1) gave a colorless oil (57.4 mg, 80%): 1H NMR (CDCl3, 400 MHz) δ 7.26− 7.19 (m, 0.73H), 7.05−7.03 (m, 0.34H), 6.62−6.60 (m, 0.62H), 6.57− 6.54 (m, 0.33H), 6.51−6.49 (m, 0.56H), 6.43−6.42 (m, 0.3H), 3.83 (d, 3H), 3.18 (s, 3H), 2.10−2.02 (m, 0.72H), 1.88−1.79 (m, 1H), 1.71−1.63 (m, 0.4H), 1.40 (s, 2.09H), 1.31 (s, 1.14H), 1.30−1.13 (m, 18H), 0.87−0.67 (m, 5H); 13C{1H} NMR (CDCl3, 100 MHz) δ 181.5, 181.3, 159.8, 156.0, 144.6, 144.5, 128.7, 126.3, 122.9, 119.4, 106.1, 105.7, 101.3, 95.9, 55.5, 55.3, 49.2, 47.9, 38.6, 36.1, 31.9, 29.8, 29.7, 29.64, 29.60, 29.58, 29.57, 29.55, 29.4, 29.3, 26.3, 26.1, 24.9, 24.5, 23.9, 22.7, 22.0, 14.1; MS (EI) 359, 191, 176. 3-Dodecyl-5-isopropyl-1,3-dimethylindolin-2-one (3ga). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (56.4 mg, 76%): 1H NMR (CDCl3, 400 MHz) δ 7.11 (d, J = 7.9 Hz, 1H), 7.02 (s, 1H), 6.75 (d, J = 7.9 Hz, 1H), 3.19 (s, 3H), 2.94−2.87 (m, 1H), 1.89−1.82 (m, 1H), 1.74−1.67 (m, 1H), 1.34 (s, 3H), 1.26−1.14 (m, 24H), 1.01−0.79 (m, 5H); 13 C{1H} NMR (CDCl3, 100 MHz) δ 180.9, 143.3, 141.2, 134.4, 125.1, 120.8, 107.5, 48.6, 38.5, 33.9, 31.9, 29.7, 29.6, 29.57, 29.53, 29.3, 29.2, 26.1, 24.4, 24.36, 24.34, 23.8, 22.7, 14.1; HRMS (ESI) m/z calcd for C25H42NO (M + H)+ 372.3261, found 372.3263. 3-Dodecyl-5-fluoro-1,3-dimethylindolin-2-one (3ha). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/ 1) gave a colorless oil (49.9 mg, 72%): 1H NMR (CDCl3, 400 MHz) δ 6.98−6.93 (m, 1H), 6.92−6.89 (m, 1H), 6.76−6.73 (m, 1H), 3.19 (s, 3H), 1.92−1.85 (m, 1H), 1.72−1.65 (m, 1H), 1.34 (s, 3H), 1.29−1.14 (m, 18H), 0.99−0.77 (m, 5H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.5, 159.9 (d, J = 238.8 Hz), 139.2, 136.1 (d, J = 7.7 Hz), 113.7 (d, J = 23.4 Hz), 110.7 (d, J = 24.3 Hz), 108.2 (d, J = 8.1 Hz), 48.9 (d, J = 1.7 Hz), 38.5, 31.9, 29.7, 29.6, 29.56, 29.54, 29.33, 29.31, 26.2, 24.4, 23.7, 22.7, 14.1; HRMS (ESI) m/z calcd for C22H35FNO (M + H)+ 348.2697, found 348.2694. 5-Bromo-3-dodecyl-1,3-dimethylindolin-2-one (3ia). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/ 1) gave a colorless oil (61.0 mg, 75%): 1H NMR (CDCl3, 400 MHz) δ 7.38 (d, J = 8.2 Hz, 1H), 7.26 (s, 1H), 6.71(d, J = 8.2 Hz, 1H), 3.19 (s, 3H), 1.92−1.84 (m, 1H), 1.72−1.64 (m, 1H), 1.33 (s, 3H), 1.29−1.14 (m, 18H), 0.98−0.78 (m, 5H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.2, 142.4, 136.5, 130.4, 125.8, 115.2, 109.3, 48.7, 38.5, 31.9, 29.7, 29.6, 29.57, 29.56, 29.34, 29.30, 26.2, 24.4, 23.7, 22.7, 14.1; HRMS (ESI) m/z calcd for C22H35BrNO (M + H)+ 408.1897, found 408.1892. 3-Dodecyl-1,3-dimethyl-5-(trifluoromethyl)indolin-2-one (3ja). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (54.8 mg, 69%): 1H NMR (CDCl3, 400 MHz) δ 7.55 (d, J = 8.1 Hz, 1H), 7.38 (s, 1H), 6.90 (d, J = 8.1 Hz, 1H), 3.24 (s, 3H), 1.95−1.87 (m, 1H), 1.78−1.70 (m, 1H), 1.37 (s, 3H), 1.30−1.14 (m, 18H), 0.99−0.77 (m, 5H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.7, 146.3, 134.9, 125.5 (q, JC−F = 3.9 Hz), 124.7 (q, JC−F = 32.3 Hz), 124.5 (q, JC−F = 270 Hz), 119.4 (q, JC−F = 3.5 Hz), 107.5, 48.5, 38.4, 31.9, 29.61, 29.60, 29.54, 29.50, 29.3, 29.2, 26.3, 24.4, 23.6, 22.7, 14.1; HRMS (ESI) m/z calcd for C23H35F3NO (M + H)+ 398.2665, found 398.2668. Ehyl 3-Dodecyl-1,3-dimethyl-2-oxoindoline-5-carboxylate (3ka). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 5/1) gave a colorless oil (50.5 mg, 63%): 1H NMR (CDCl3, 400 MHz) δ 8.04−8.01 (m, 1H), 7.84−7.83 (m, 1H), 6.86 (d, J = 8.2 Hz, 1H), 4.41−4.35 (q, 2H), 3.24 (s, 3H), 1.95−1.87 (m, 1H), 1.80− 1.72 (m, 1H), 1.41 (t, J = 7.2 Hz, 3H), 1.37(s, 3H), 1.30−1.13 (m, 18H), 0.97−0.85 (m, 5H); 13C{1H} NMR (CDCl3, 100 MHz) δ 181.2, 166.6, 147.4, 134.2, 130.4, 124.7, 123.7, 107.3, 60.9, 48.4, 38.5, 31.9, 29.69, 29.61, 29.60, 29.5, 29.33, 29.32, 29.30, 24.5, 23.7, 22.7, 14.4, 14.1; HRMS (ESI) m/z calcd for C25H40NO3 (M + H)+ 402.3003, found 402.3007. 3-Dodecyl-1,3-dimethyl-7-phenylindolin-2-one (3la). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/ 1) gave a colorless oil (61.6 mg, 76%): 1H NMR (CDCl3, 400 MHz) δ 7.42−7.34 (m, 1H), 7.17−7.14 (m, 1H), 7.09−7.04 (m, 1H), 2.72 (s, 3H), 1.95−1.87 (m, 1H), 1.78−1.70 (m, 1H), 1.38 (s, 3H), 1.29−1.17 (m, 18H), 1.03−0.96 (m, 2H), 0.87 (t, J = 6.8 Hz, 3H); 13C{1H} 5008

DOI: 10.1021/acs.joc.7b00663 J. Org. Chem. 2017, 82, 5005−5010

Note

The Journal of Organic Chemistry 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.9, 143.3, 134.4, 127.6, 122.5, 122.4, 107.8, 48.4, 38.8, 26.6, 26.1, 23.8, 22.9, 13.8. 1,3-Dimethyl-3-pentylindolin-2-one (3ad).11 Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (34.6 mg, 75%): 1H NMR (CDCl3, 400 MHz) δ 7.28− 7.24 (m, 1H), 7.18−7.15 (m, 1H), 7.08−7.04 (m, 1H), 6.84 (d, J = 7.8 Hz, 1H), 3.21 (s, 3H), 1.92−1.84 (m, 1H), 1.75−1.68 (m, 1H), 1.34 (s, 3H), 1.19−1.10 (m, 4H), 1.03−0.93 (m, 1H), 0.85−0.80 (m, 1H), 0.77 (t, J = 6.9 Hz, 3H); 13C{1H}NMR (CDCl3, 100 MHz) δ 180.9, 143.3, 134.3, 127.6, 122.5, 122.4, 107.8, 48.5, 38.5, 31.9, 26.1, 24.1, 23.8, 22.3, 13.9. 3-Hexyl-1,3-dimethylindolin-2-one (3ae).7 Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (35.8 mg, 73%): 1H NMR (CDCl3, 400 MHz) δ 7.28− 7.24 (m, 1H), 7.18−7.15 (m, 1H), 7.08−7.04 (m, 1H), 6.84 (d, J = 7.7 Hz, 1H), 3.21 (s, 3H), 1.92−1.84 (m, 1H), 1.76−1.68 (m, 1H), 1.34 (s, 3H), 1.21−1.09 (m, 6H), 1.02−0.84 (m, 2H), 0.80 (t, J = 6.9 Hz, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.9, 143.3, 134.3, 127.6, 122.5, 122.4, 107.8, 48.5, 38.5, 31.5, 29.4, 26.1, 24.4, 23.8, 22.5, 14.0. 3-Heptyl-1,3-dimethylindolin-2-one (3af). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (39.3 mg, 76%): 1H NMR (CDCl3, 400 MHz) δ 7.28− 7.24 (m, 1H), 7.17−7.15 (m, 1H), 7.08−7.04 (m, 1H), 6.84 (d, J = 7.8 Hz, 1H), 3.21 (s, 3H), 1.92−1.84 (m, 1H), 1.75−1.68 (m, 1H), 1.34 (s, 3H), 1.22−1.14 (m, 8H), 1.02−0.85 (m, 2H), 0.82 (t, J = 6.9 Hz, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.9, 143.3, 134.3, 127.6, 122.5, 122.4, 107.8, 48.5, 38.5, 31.8, 29.7, 28.9, 26.1, 24.5, 23.8, 22.6, 14.0; HRMS (ESI) m/z calcd for C17H26NO (M + H)+ 260.2009, found 260.2007. 1,3-Dimethyl-3-octylindolin-2-one (3ag).7 Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (40.9 mg, 75%): 1H NMR (CDCl3, 400 MHz) δ 7.28− 7.24 (m, 1H), 7.16 (d, J = 6.7 Hz, 1H), 7.08−7.04 (m, 1H), 6.83 (d, J = 7.7 Hz, 1H), 3.21 (s, 3H), 1.92−1.84 (m, 1H), 1.75−1.68 (m, 1H), 1.34 (s, 3H), 1.26−1.14 (m, 10H), 1.00−0.78 (m, 5H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.9, 143.3, 134.3, 127.6, 122.5, 122.4, 107.8, 48.5, 38.5, 31.8, 29.7, 29.3, 29.2, 26.1, 24.5, 23.8, 22.6, 14.1. 1,3-Dimethyl-3-nonylindolin-2-one (3ah). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (48.8 mg, 85%): 1H NMR (CDCl3, 400 MHz) δ 7.28− 7.24 (m, 1H), 7.17−7.15 (m, 1H), 7.08−7.04 (m, 1H), 6.83 (d, J = 7.8 Hz, 1H), 3.21 (s, 3H), 1.92−1.84 (m, 1H), 1.75−1.68 (m, 1H), 1.34 (s, 3H), 1.26−1.14 (m, 12H), 1.00−0.76 (m, 5H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.9, 143.3, 134.3, 127.6, 122.5, 122.4, 107.8, 48.5, 38.6, 31.8, 29.7, 29.5, 29.3, 29.2, 26.1, 24.5, 23.8, 22.6, 14.1; HRMS (ESI) m/z calcd for C19H30NO (M + H)+ 288.2322, found 288.2321. 3-Decyl-1,3-dimethylindolin-2-one (3ai). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (48.2 mg, 80%): 1H NMR (CDCl3, 400 MHz) δ 7.28− 7.23 (m, 1H), 7.16 (d, J = 6.8 Hz, 1H), 7.08−7.04 (m, 1H), 6.83 (d, J = 7.8 Hz, 1H), 3.21 (s, 3H), 1.91−1.84 (m, 1H), 1.75−1.67 (m, 1H), 1.34 (s, 3H), 1.27−1.14 (m, 14H), 1.00−0.78 (m, 5H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.9, 143.3, 134.3, 127.5, 122.5, 122.4, 107.8, 48.5, 38.6, 31.9, 29.8, 29.6, 29.5, 29.3, 29.2, 26.1, 24.5, 23.8, 22.7, 14.1; HRMS (ESI) m/z calcd for C20H32NO (M + H)+ 302.2478, found 302.2479. 1,3-Dimethyl-3-tetradecylindolin-2-one (3aj). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (56.4 mg, 79%): 1H NMR (CDCl3, 400 MHz) δ 7.28− 7.23 (m, 1H), 7.17−7.15 (m, 1H), 7.08−7.04 (m, 1H), 6.83 (d, J = 7.7 Hz, 1H), 3.21 (s, 3H), 1.91−1.84 (m, 1H), 1.75−1.67 (m, 1H), 1.34 (s, 3H), 1.29−1.13 (m, 22H), 0.99−0.77 (m, 5H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.9, 143.3, 134.4, 127.5, 122.5, 122.4, 107.8, 48.5, 38.5, 31.9, 29.8, 29.7, 29.67, 29.65, 29.61, 29.57, 29.56, 29.4, 29.3, 26.1, 24.5, 23.8, 22.7, 14.1; HRMS (ESI) m/z calcd for C24H40NO (M + H)+ 358.3104, found 358.3106. 3-Hexadecyl-1,3-dimethylindolin-2-one (3ak). Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/1) gave a colorless oil (63.9 mg, 83%): 1H NMR (CDCl3, 400 MHz) δ

7.28−7.23 (m, 1H), 7.17−7.15 (m, 1H), 7.08−7.04 (m, 1H), 6.83 (d, J = 7.7 Hz, 1H), 3.21 (s, 3H), 1.92−1.84 (m, 1H), 1.75−1.67 (m, 1H), 1.34 (s, 3H), 1.30−1.14 (m, 26H), 0.99−0.78 (m, 5H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.9, 143.3, 134.3, 127.5, 122.5, 122.4, 107.8, 48.4, 38.5, 31.9, 29.8, 29.7, 29.67, 29.62, 29.58, 29.56, 29.4, 29.3, 26.1, 24.4, 23.8, 22.7, 14.1; HRMS (ESI) m/z calcd for C26H44NO (M + H)+ 386.3417, found 386.3420. 1,3-Dimethyl-3-(3-phenylpropyl)indolin-2-one (3al).7 Flash column chromatography on silica gel (petroleum ether/ethyl acetate 10/ 1) gave a colorless oil (49.6 mg, 89%): 1H NMR (CDCl3, 400 MHz) δ 7.26−7.19 (m, 3H), 7.15−7.11 (m, 2H), 7.06−7.02 (m, 3H), 6.82 (d, J = 7.8 Hz, 1H), 3.19 (s, 3H), 2.56−2.40 (m, 2H), 1.99−1.92 (m, 1H), 1.81−1.74 (m, 1H), 1.38−1.25 (m, 4H), 1.20−1.09 (m, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 180.7, 143.3, 141.9, 134.0, 128.4, 128.2, 127.7, 125.7, 122.5, 107.9, 48.4, 38.2, 35.9, 26.4, 26.1, 23.9.

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b00663. Mechanism study, 1H and 13C NMR spectra of compounds 3aa−3qa and 3ab−3al (PDF)

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AUTHOR INFORMATION

Corresponding Authors

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

Jin-Tao Yu: 0000-0002-0264-9407 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the National Natural Science Foundation of China (21602086 and 21672028), the Natural Science Foundation for Colleges and Universities of Jiangsu Province (16KJB150002), and Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology (BM2012110) for financial support.

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REFERENCES

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DOI: 10.1021/acs.joc.7b00663 J. Org. Chem. 2017, 82, 5005−5010