Palladium-Catalyzed Regioselective Olefination of O-Acetyl

Jun 14, 2018 - A practical palladium-catalyzed ortho-olefination of O-acetyl cyanohydrins assisted by synergetic directing groups has been developed. ...
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Cite This: J. Org. Chem. 2018, 83, 8265−8271

Palladium-Catalyzed Regioselective Olefination of O‑Acetyl Cyanohydrins Qiu-Ju Liang,† Bing Jiang,† Yun-He Xu,*,† and Teck-Peng Loh*,†,‡ †

Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371

‡

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S Supporting Information *

ABSTRACT: A practical palladium-catalyzed ortho-olefination of O-acetyl cyanohydrins assisted by synergetic directing groups has been developed. Thus, a range of olefinated Oacetyl cyanohydrins were synthesized in moderate to good yields. The reaction occurs efficiently with high regioselectivity and with a satisfactory tolerance of functional groups.

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INTRODUCTION Transition-metal-catalyzed direct C−H functionalization reactions have made a great progress and become powerful methods for construction of new carbon−carbon and carbon− heteroatom bonds.1,2 During the past several decades, the application of various directing groups to enhance the reactivity of substrates and present a catalyst metal center to a specific site is the most prevalent and efficient strategy.3 Therefore, various directing groups have been continuously developed for Pd(II),4 Rh(III),5 Ru(II),6 and other7 catalytic systems. It is noteworthy that the majority of directing groups reported are not easily removable or convertible to other useful functionalities, which will greatly compromise the application of the reactions. Therefore, from the viewpoint of synthetic practicality, the easily accessible and convertible directing groups are highly desirable8 since they will provide an additional route to introduce diversity and complexity into the final products. Therefore, we fixed our attention on the cyanohydrins containing cyano and ester moieties that are ready for accessibility and potential diversity in transformation.9 A pioneering work of meta-selective C−H olefination based on the weak coordination between Pd(II) and the cyano group was reported by Yu’s group in 2012.10 In addition, many examples on transition-metal-catalyzed direct C−H functionalization assisted by different carbonyl groups were also reported.11 Inspired by these works, herein we would like to communicate the results on palladium-catalyzed orthoolefination of O-acetyl cyanohydrins (Scheme 1).

Scheme 1. Transitional-Metal-Catalyzed Olefination of Arenes Assisted by Cyano or Carbonyl Group

First, 10 mol % of Pd(PPh3)2Cl2 and 20 mol % of N-acetylwere used in the presence of 2.0 equiv of Ag2CO3 as oxidant, and the desired product 3a was obtained in 18% yield (Table 1, entry 1). Furthermore, various palladium catalysts like Pd(MeCN)4BF4, [Pd(C3H5)Cl]2, and Pd(OAc)2 were tested for this reaction. It was encouraging to find that Pd(OAc)2 could provide the desired product 3a in 62% yield in HFIP (hexafluoroisopropanol) solution (Table 1, entry 4). Because the oxidants commonly were critical for the coupling efficiency of the C−H activation reactions, subsequent optimization of different oxidants was conducted. Among various oxidants screened, Cu(OAc)2 and Ag2O were ineffective to promote the reaction. Silver acetate (AgOAc) did not give a better yield than Ag2CO3 (Table 1, entries 5−7). Other N-protected amino acid ligands were able to work in this L-glycine

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RESULTS AND DISCUSSION Initially, the coupling reaction of cyano(o-tolyl)methyl acetate 1a with ethyl acrylate 2a at 80 °C was chosen as the model reaction to optimize the reaction conditions, and the results are summarized in Table 1. According to the reaction conditions developed by Yu and co-workers, we commenced the study via ligand-accelerated C−H olefination strategy.12 © 2018 American Chemical Society

Received: April 19, 2018 Published: June 14, 2018 8265

DOI: 10.1021/acs.joc.8b00991 J. Org. Chem. 2018, 83, 8265−8271

Article

The Journal of Organic Chemistry Table 1. Optimization of Reaction Conditions of C−H Olefination of O-Acetyl Cyanohydrin 1aa,b

entry

catalyst

1

Pd(PPh3)2Cl2

2

Pd(MeCN)4BF4

3

[Pd (C3H5)Cl]2

4

Pd(OAc)2

5

Pd(OAc)2

6

Pd(OAc)2

7

Pd(OAc)2

8

Pd(OAc)2

9

Pd(OAc)2

10

Pd(OAc)2

11

Pd(OAc)2

12

Pd(OAc)2

13 14 15 16 17

Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2 Pd(OAc)2

ligand Ac-GlyOH Ac-GlyOH Ac-GlyOH Ac-GlyOH Ac-GlyOH Ac-GlyOH Ac-GlyOH Ac-IleOH Ac-PheOH Ac-LeuOH Ac-ValOH Ac-AlaOH L1 L2 L3 L4

oxidant

yield (%)

Scheme 2. Synergetic Effect of Directing Groups

selectivity o/ (m + p)

Ag2CO3

18

92:8

Ag2CO3

43

86:14

Ag2CO3

36

86:14

Ag2CO3

62 (63)c

90:10

AgOAc

48

72:28

Cu(OAc)2

trace

Ag2O

nr

Ag2CO3

19

77:23

Ag2CO3

37

85:15

Ag2CO3

28

75:25

Ag2CO3

25

77:23

Ag2CO3

35

88:12

Ag2CO3 Ag2CO3 Ag2CO3 Ag2CO3 Ag2CO3

18 14 42 16 nr

85:15 91:9 92:8 82:18

coupling reaction. This result possibly accounts for the enhanced positioning effect of double groups in the flexible O-acetyl cyanohydrins. With the optimized reaction conditions in hand, the scope of substrates 1 was investigated to react with ethyl acrylate (Table 2). Accordingly, a variety of O-acetyl cyanohydrins possessing electron-donating or withdrawing groups was employed. Table 2. Reaction Scope of Palladium-Catalyzed C−H Olefination of O-Acetyl Cyanohydrinsa,b,c

a Unless otherwise noted, the reaction was carried out with use of 1a (0.5 mmol), 2a (1.0 mmol), catalyst (0.05 mmol), ligand (0.10 mmol), and oxidant (2.0 equiv) in the indicated solvent (2 mL) at 80 °C after being stirred for 24 h under air. bThe yield was determined by 1H NMR using CH2Br2 as an internal standard. cThe isolated yield is in parentheses. a

Unless otherwise noted, the reactions were carried out with use of 1 (0.5 mmol), 2a (1.0 mmol), Pd(OAc)2 (0.05 mmol), Ac-Gly-OH (0.10 mmol), and Ag2CO3 (2.0 equiv) in HFIP (2 mL) at 80 °C after being stirred for 24 h under air. bIsolated yield. cThe reaction time is 48 h.

transformation but led to obvious decreased yields (Table 1, entries 8−16). Remarkably, the control experiment proved that the presence of N-protected amino acid as ligand in this coupling reaction was essential to improve the product’s yield (Table 1, entry 17). To explore the role of a possible directing group during this coupling process, plain benzyl acetate 1n and 2-phenylacetonitrile 1o were synthesized and subjected to reaction with ethyl acrylate under the optimized reaction conditions, respectively. The results showed that both substrates could couple with ethyl acrylate. Unfortunately, in both cases, a mixture of ortho-, meta- and para-olefinated products would be generated without apparently biased regioselectivity (Scheme 2, eqs 1 and 2). Based on these results, we concluded that acetoxy and cyano groups in the substrate play a synergetic directing role for controlling the regioselectivity in this

The results showed that the substrates bearing different substituents at the ortho-position of the directing group such as alkyl, methoxy, chloro, fluoro, and trifluoromethyl groups were all well tolerated to afford the corresponding monoolefinated products in 40−62% yields and with high regioselectivities (Table 2, 3a−e). When the acetoxy group in the substrate 1a was changed to a tert-butyloxy or benzoyloxy group, the desired products were both generated in good yields under the standard conditions (Table 2, 3f,g). For the cases of O-acetyl cyanohydrins without a substituent at the ortho-position of the directing group, a mixture of mono- and diolefinated products 8266

DOI: 10.1021/acs.joc.8b00991 J. Org. Chem. 2018, 83, 8265−8271

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The Journal of Organic Chemistry

cyanohydrins assisted by the synergetic directing effect of acetoxy and cyano functionalities. The current catalytic system was compatible with various functional groups, affording the ortho-olefinated products in acceptable yields and with good regioselectivities. This reaction provides an attractive and efficient approach for the synthesis of multifunctionalized arenes.

was obtained. Significantly, the site of substitution on the phenyl ring greatly affected the ratio of mono- and diolefinated products, possibly due to their steric differences (Table 2, 3h− l). Moreover, the only ortho-olefinated product 3m was obtained in 57% isolated yield when the more challenging trisubstituted arene 1m was tested in current reaction (Table 2, 3m). Next, the scope and limitation of the coupling partners were examined by employing cyano(o-tolyl)methyl acetate 1a as the substrate. As shown in Table 3, except for ethyl acrylate, other

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EXPERIMENTAL SECTION

General Information. Unless otherwise noted, all reagents were purchased from commercial suppliers and used without further purification. 1H NMR and 13C NMR spectra were recorded at 25 °C on a Bruker Advance 400 M NMR spectrometers (CDCl3 as solvent). Chemical shifts for 1H NMR spectra are reported as δ in units of parts per million (ppm) downfield from SiMe4 (δ 0.0) and relative to the signal of SiMe4 (δ 0.00 singlet). Multiplicities are given as s (singlet); d (doublet); t (triplet); q (quartet); dd (doublet of doublets); dt (doublet of triplets); m (multiplets). Coupling constants are reported as J values in Hz. 13C NMR spectra are reported as δ in units of parts per million (ppm) downfield from SiMe4 (δ 0.0) and relative to the signal of chloroform-d (δ 77.26 triplet). High-resolution mass spectral analysis (HRMS) was performed on a Waters XEVO G2 Q-TOF (Waters Corp.). Flash chromatography was performed using 200− 300 mesh silica gel with the indicated solvent system. The following starting materials were purchased from chemical suppliers: 2a−e and 1o. These starting materials were synthesized following literature procedures: 1a, 1f−k,13 1b−e, 1l, 1m,14 and 1n.15 NMR data for 1a, 1b, and 1h−l can be found in the literature. Cyano(2-fluorophenyl)methyl acetate (1c). 5% EtOAc/hexane as an elution gradient to yield 1c (5 mmol scale 0.8886 g, 92%) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 7.63 (td, J = 7.5, 1.7 Hz, 1H), 7.50−7.43 (m, 1H), 7.25 (td, J = 7.6, 1.0 Hz, 1H), 7.14 (ddd, J = 9.6, 8.4, 1.0 Hz, 1H), 6.61 (s, 1H), 2.15 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.7, 160.1 (d, JC−F = 251.8 Hz), 132.6 (d, JC−F = 8.3 Hz), 129.6 (d, JC−F = 2.2 Hz), 124.9 (d, JC−F = 4.1 Hz), 119.3 (d, JC−F = 13.2 Hz), 116.2 (d, JC−F = 20.5 Hz), 115.4, 57.4 (d, JC−F = 4.8 Hz), 20.2; HRMS (ESI) m/z [M + Na]+ calcd for C10H8FNO2Na 216.0437, found 216.0440. Cyano(2-(trifluoromethyl)phenyl)methyl acetate (1d). 5% EtOAc/hexane as an elution gradient to yield 1d (5 mmol scale 0.9727 g, 80%) as a yellow solid: mp 46−47 °C; 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 7.8 Hz, 1H), 7.78−7.69 (m, 2H), 7.61 (t, J = 7.7 Hz, 1H), 6.69 (s, 1H), 2.18 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.4, 133.0, 130.7, 130.1, 129.8 (q, JC−F = 1.5 Hz), 128.3 (q, JC−F = 31.6 Hz), 126.8 (q, JC−F = 5.5 Hz), 123.5 (q, JC−F = 274.5 Hz), 115.5, 59.3 (q, JC−F = 2.8 Hz), 20.2; HRMS (ESI) m/z [M + Na]+ calcd for C11H8F3NO2Na 266.0405, found 266.0402. Cyano(2-methoxyphenyl)methyl Acetate (1e). 5% EtOAc/hexane as an elution gradient to yield 1e (5 mmol scale 0.7695 g, 75%) as a yellow solid: mp 57−58 °C; 1H NMR (400 MHz, CDCl3) δ 7.56 (dd, J = 7.6, 1.6 Hz, 1H), 7.42 (td, J = 8.3, 1.7 Hz, 1H), 7.03 (td, J = 7.6, 0.8 Hz, 1H), 6.94 (d, J = 8.3 Hz, 1H), 6.70 (s, 1H), 3.87 (s, 3H), 2.16 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.9, 156.7, 131.8, 128.7, 120.9, 119.9, 116.3, 111.1, 58.2, 55.7, 20.4; HRMS (ESI) m/z [M + Na]+ calcd for C11H11NO3Na 228.0637, found 228.0640. Cyano(o-tolyl)methyl Pivalate (1f). 2−5% EtOAc/hexane as an elution gradient to yield 1f (5 mmol scale 1.0293 g, 89%) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 7.55 (dd, J = 7.5, 1.2 Hz, 1H), 7.35 (td, J = 7.5, 1.4 Hz, 1H), 7.29 (d, J = 7.5 Hz, 1H), 7.24 (d, J = 6.3 Hz, 1H), 6.48 (s, 1H), 2.43 (s, 3H), 1.25 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 176.4, 136.6, 131.3, 130.3, 130.1, 128.3, 126.7, 116.1, 61.2, 38.9, 26.9, 18.8; HRMS (ESI) m/z [M + Na]+ calcd for C14H17NO2Na 254.1157, found 254.1159. Cyano(o-tolyl)methyl benzoate (1g). 5% EtOAc/hexane as an elution gradient to yield 1g (5 mmol scale 0.9674 g, 77%) as pale yellow solid: mp 45−46 °C; 1H NMR (400 MHz, CDCl3) δ 8.08− 8.05 (m, 2H), 7.66 (dd, J = 7.6, 1.3 Hz, 1H), 7.63−7.58 (m, 1H), 7.49−7.43 (m, 2H), 7.37 (td, J = 7.4, 1.5 Hz, 1H), 7.32 (dd, J = 7.5, 1.1 Hz, 1H), 7.30−7.25 (m, 1H), 6.76 (s, 1H), 2.49 (s, 3H); 13C

Table 3. Reactions of Palladium-Catalyzed C−H Olefination of 1a with Electron-Deficient Alkenesa,b

a Unless otherwise noted, the reactions were carried out with use of 1a (0.5 mmol), 2 (1.0 mmol), Pd(OAc)2 (0.05 mmol), Ac-Gly-OH (0.10 mmol), and Ag2CO3 (2.0 equiv) in HFIP (2 mL) at 80 °C after being stirred for 24 h under air. bIsolated yield.

readily available acrylates such as methyl acrylate and n-butyl acrylate also reacted smoothly with 1a and provided the corresponding products in 69% and 66% yields and with highly regioselectivities, respectively. When the compatibility of other vinyl derivatives such as ethyl vinylketone and vinylsulfonybenzene was tested for this reaction, the corresponding products were obtained in moderate yields, respectively. However, the product 4e was only isolated in 11% yield, probably due to the instability of acrolein under the strong oxidative condition. Furthermore, the derivation reactions of compound 3b were investigated. First, the acetyl protecting group could be selectively removed by using p-toluenesulfonic acid monohydrate in ethanol solution (Scheme 3, eq 1). In addition, the 2-acyloxy amide product 5b could be obtained in 98% yield via the Ritter reaction (Scheme 3, eq 2).

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CONCLUSION In summary, we have developed a novel method for Pdcatalyzed C−H bond olefination reaction of O-acetyl Scheme 3. Derivation of Compound 3b

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DOI: 10.1021/acs.joc.8b00991 J. Org. Chem. 2018, 83, 8265−8271

Article

The Journal of Organic Chemistry NMR (101 MHz, CDCl3) δ 164.6, 136.8, 134.1, 131.4, 130.5, 130.1, 123.0, 128.7, 128.6, 128.1, 126.8, 116.1, 61.7, 19.0; HRMS (ESI) m/z [M + Na]+ calcd for C16H13NO2Na 274.0844, found 274.0843. Cyano(5-fluoro-2-methylphenyl)methyl Acetate (1m). 5% EtOAc/hexane as an elution gradient to yield 1m (5 mmol scale 0.7356 g, 71%) as pale yellow oil: 1H NMR (400 MHz, CDCl3) δ 7.28 (dd, J = 9.1, 2.7 Hz, 1H), 7.21 (dd, J = 8.5, 5.6 Hz, 1H), 7.05 (td, J = 8.3, 2.7 Hz, 1H), 6.46 (s, 1H), 2.39 (s, 3H), 2.19 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.7, 161.2 (d, JC−F = 264.0 Hz), 132.8 (d, JC−F = 7.73 Hz), 132.0 (d, JC−F = 3.53 Hz), 131.5 (d, JC−F = 7.38 Hz), 117.2 (d, JC−F = 20.77 Hz), 115.5, 115.1 (d, JC−F = 23.35 Hz), 60.3 (d, JC−F = 1.81 Hz), 20.3, 18.1; HRMS (ESI) m/z [M + Na]+ calcd for C11H10FNO2Na 230.0593, found 230.0600. General Procedure for the Synthesis of the Coupling Product 3 or 4. A 25 mL sealed tube was charged with 1 (0.5 mmol), coupling partner 2 (1.0 mmol), Pd(OAc)2 (11.3 mg, 0.05 mmol), Ac-Gly-OH (11.7 mg, 0.10 mmol), Ag2CO3 (275.8 mg, 1.0 mmol), and HFIP (2.0 mL). The vial was stirred at 80 °C for 24 h. The mixture was then cooled to room temperature, diluted with EtOAc (5 mL), filtered through a Celite pad, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane (10%−15% gradient) to afford the desired olefinated product 3 or 4. Ethyl (E)-3-(2-(acetoxy(cyano)methyl)-3-methylphenyl)acrylate (3a): yield (90.5 mg, 63%) as a pale yellow solid: mp 69−70 °C. 1 H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 15.6 Hz, 1H), 7.43 (d, J = 7.6 Hz, 1H), 7.35 (t, J = 7.7 Hz, 1H), 7.31−7.25 (m, 1H), 6.87 (s, 1H), 6.33 (d, J = 15.6 Hz, 1H), 4.29 (q, J = 7.1 Hz, 2H), 2.58 (s, 3H), 2.15 (s, 3H), 1.35 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 168.6, 166.1, 141.3, 138.3, 135.6, 132.8, 130.6, 128.6, 126.3, 123.1, 115.6, 60.8, 58.0, 20.3, 20.0, 14.3; HRMS (ESI) m/z [M + Na]+ calcd for C16H17NO4Na 310.1055, found 310.1055. Ethyl (E)-3-(2-(acetoxy(cyano)methyl)-3-chlorophenyl)acrylate (3b): yield (96.9 mg, 63%) as a pale yellow solid; mp 55−56 °C; 1 H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 15.7 Hz, 1H), 7.53 (dd, J = 7.7, 1.2 Hz, 1H), 7.49 (dd, J = 8.1, 1.4 Hz, 1H), 7.42 (t, J = 7.9 Hz, 1H), 7.14 (s, 1H), 6.38 (d, J = 15.7 Hz, 1H), 4.30 (q, J = 7.1 Hz, 2H), 2.17 (s, 3H), 1.35 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 168.3, 165.7, 140.0, 137.6, 135.1, 131.7, 131.2, 127.8, 127.0, 123.8, 114.9, 60.9, 58.1, 20.2, 14.2; HRMS (ESI) m/z [M + Na]+ calcd for C15H14ClNO4Na 330.0509, found 330.0506. Ethyl (E)-3-(2-(acetoxy(cyano)methyl)-3-fluorophenyl)acrylate (3c): yield (87.4 mg, 60%) as a pale yellow solid; mp 68−69 °C; 1 H NMR (400 MHz, CDCl3) δ 8.15 (d, J = 15.7 Hz, 1H), 7.52−7.42 (m, 2H), 7.20 (td, J = 8.7, 7.9 Hz, 1H), 6.87 (d, J = 1.7 Hz, 1H), 6.42 (d, J = 15.7 Hz, 1H), 4.30 (q, J = 7.1 Hz, 2H), 2.17 (s, 3H), 1.36 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 168.4, 165.7, 160.7 (d, JC−F = 253.1 Hz), 139.0 (d, JC−F = 3.0 Hz), 136.9 (d, JC−F = 1.8 Hz), 132.5 (d, JC−F = 9.5 Hz), 124.1, 123.8 (d, JC−F = 3.4 Hz), 118.1 (d, JC−F = 12.6 Hz), 117.2 (d, JC−F = 22.4 Hz), 115.0, 61.0, 54.4 (d, JC−F = 7.4 Hz), 20.3, 14.2; HRMS (ESI) m/z [M + Na]+ calcd for C15H14FNO4Na 314.0804, found 314.0812. Ethyl (E)-3-(2-(acetoxy(cyano)methyl)-3-(trifluoromethyl)phenyl)acrylate (3d): yield (92.1 mg, 54%) as a yellow solid: mp 51−52 °C; 1H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 15.7 Hz, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.69 (d, J = 7.8 Hz, 1H), 7.54 (t, J = 7.9 Hz, 1H), 6.77 (s, 1H), 6.34 (d, J = 15.7 Hz, 1H), 4.21 (q, J = 7.1 Hz, 2H), 2.08 (s, 3H), 1.26 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 168.1, 165.6, 140.0, 137.9, 132.4, 130.9, 129.5 (q, JC−F = 30.9 Hz), 128.0, 127.4 (q, JC−F = 31.1 Hz), 124.0, 123.3 (q, JC−F = 274.6 Hz), 114.7, 60.9, 57.1 (q, JC−F = 3.5 Hz), 20.1, 14.2; HRMS (ESI) m/z [M + Na]+ calcd for C16H14F3NO4Na 364.0773, found 364.0775. Ethyl (E)-3-(2-(acetoxy(cyano)methyl)-3-methoxyphenyl)acrylate (3e): yield (60.7 mg, 40%) as a pale yellow solid; mp 56− 57 °C; 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 15.7 Hz, 1H), 7.43 (t, J = 8.1 Hz, 1H), 7.22 (d, J = 7.8 Hz, 1H), 7.09 (s, 1H), 6.99 (d, J = 8.3 Hz, 1H), 6.37 (d, J = 15.7 Hz, 1H), 4.29 (q, J = 7.1 Hz, 2H), 3.92 (d, J = 2.1 Hz, 3H), 2.14 (s, 3H), 1.35 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 168.7, 166.0, 157.4, 140.6, 136.5, 131.8, 122.8,

120.1, 118.7, 116.0, 112.5, 60.7, 56.3, 55.0, 20.4, 14.3; HRMS (ESI) m/z [M + Na]+ calcd for C16H17NO5Na 326.1004, found 326.1008. Ethyl (E)-3-(2-(cyano(pivaloyloxy)methyl)-3-methylphenyl)acrylate (3f): yield (97.2 mg, 59%) as a yellow oil; 1H NMR (400 MHz, CDCl3) δ 8.31 (d, J = 15.7 Hz, 1H), 7.46 (d, J = 7.6 Hz, 1H), 7.35 (t, J = 7.7 Hz, 1H), 7.26 (d, J = 7.1 Hz, 1H), 6.83 (s, 1H), 6.35 (d, J = 15.7 Hz, 1H), 4.29 (q, J = 7.1 Hz, 2H), 2.58 (s, 3H), 1.34 (t, J = 7.1 Hz, 3H), 1.22 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 176.1, 166.0, 141.3, 138.0, 135.4, 132.8, 130.5, 128.9, 126.2, 122.6, 115.7, 60.7, 58.1, 38.9, 26.8, 19.9, 14.3; HRMS (ESI) m/z [M + Na]+ calcd for C19H23NO4Na 352.1525, found 352.1522. (E)-Cyano(2-(3-ethoxy-3-oxoprop-1-en-1-yl)-6-methylphenyl)methyl benzoate (3g): yield (106.6 mg, 61%) as a yellow oil; 1H NMR (400 MHz, CDCl3) δ 8.45 (d, J = 15.6 Hz, 1H), 8.08−8.02 (m, 2H), 7.62−7.55 (m, 1H), 7.43 (t, J = 7.8 Hz, 3H), 7.34 (t, J = 7.7 Hz, 1H), 7.27 (d, J = 7.4 Hz, 1H), 7.15 (s, 1H), 6.35 (d, J = 15.6 Hz, 1H), 4.31 (qd, J = 7.1, 1.2 Hz, 2H), 2.66 (s, 3H), 1.35 (t, J = 7.1 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 166.1, 164.1, 141.5, 138.2, 135.6, 134.2, 132.8, 130.7, 130.1, 128.9, 128.7, 127.9, 126.3, 122.9, 115.7, 60.8, 58.5, 20.1, 14.3; HRMS (ESI) m/z [M + Na]+ calcd for C21H19NO4Na 372.1212, found 372.1213. Ethyl (E)-3-(2-(acetoxy(cyano)methyl)phenyl)acrylate (3h): yield (57.4 mg, 42%) as a yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 15.7 Hz, 1H), 7.71−7.60 (m, 2H), 7.54−7.45 (m, 2H), 6.61 (s, 1H), 6.39 (d, J = 15.7 Hz, 1H), 4.29 (q, J = 7.1 Hz, 2H), 2.17 (s, 3H), 1.35 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 168.6, 165.9, 139.2, 134.0, 130.9, 130.4, 130.1, 129.2, 127.8, 123.1, 115.6, 60.9, 60.64 20.3, 14.3; HRMS (ESI) m/z [M + Na]+ calcd for C15H15NO4Na 296.0899, found 296.0903. Diethyl 3,3′-(2-(acetoxy(cyano)methyl)-1,3-phenylene)(2E,2′E)diacrylate (3h′): yield (33.4 mg, 18%) as a yellow solid: mp 63−64 °C; 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 15.6 Hz, 2H), 7.59 (d, J = 7.7 Hz, 2H), 7.53−7.47 (m, 1H), 6.85 (s, 1H), 6.36 (d, J = 15.7 Hz, 2H), 4.30 (q, J = 7.1 Hz, 4H), 2.16 (s, 3H), 1.36 (t, J = 7.1 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 168.4, 165.8, 140.3, 136.1, 131.1, 129.5, 128.4, 124.3, 115.2, 61.0, 57.8, 20.3, 14.3; HRMS (ESI) m/z [M + Na]+ calcd for C20H21NO6Na 394.1266, found 394.1270. Ethyl (E)-3-(2-(cyano(pivaloyloxy)methyl)phenyl)acrylate (3i): yield (60.0 mg, 38%) as a yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 15.7 Hz, 1H), 7.66 (dt, J = 6.0, 3.7 Hz, 2H), 7.52−7.45 (m, 2H), 6.56 (s, 1H), 6.40 (d, J = 15.7 Hz, 1H), 4.28 (q, J = 7.1 Hz, 2H), 1.34 (t, J = 7.1 Hz, 3H), 1.24 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 176.1, 165.9, 139.4, 134.0, 130.8, 130.4, 130.3, 129.1, 127.8, 122.7, 115.6, 61.1, 60.8, 38.9, 26.8, 14.3; HRMS (ESI) m/z [M + Na]+ calcd for C18H21NO4Na 338.1368, found 338.1369. Diethyl 3,3′-(2-(cyano(pivaloyloxy)methyl)-1,3-phenylene)(2E,2′E)-diacrylate (3i′): yield (51.7 mg, 25%) as pale yellow solid; mp 58−59 °C; 1H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 15.7 Hz, 2H), 7.59 (d, J = 7.6 Hz, 2H), 7.52−7.46 (m, 1H), 6.80 (s, 1H), 6.36 (d, J = 15.7 Hz, 2H), 4.30 (q, J = 7.1 Hz, 4H), 1.38−1.32 (m, 6H), 1.22 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 175.8, 165.7, 140.3, 136.0, 130.9, 129.4, 128.8, 124.2, 115.3, 60.9, 58.1, 38.9, 26.8, 14.3; HRMS (ESI) m/z [M + Na]+ calcd for C23H27NO6Na 436.1736, found 436.1739. Ethyl (E)-3-(2-(acetoxy(cyano)methyl)-4-methylphenyl)acrylate (3j): yield (84.8 mg, 59%) as a yellow solid; mp 45−46 °C; 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 15.7 Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.39 (s, 1H), 7.22−7.19 (m, 1H), 6.51 (s, 1H), 6.27 (d, J = 15.6 Hz, 1H), 4.19 (q, J = 7.1 Hz, 2H), 2.33 (s, 3H), 2.08 (s, 3H), 1.25 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 168.7, 166.2, 141.1, 139.2, 131.6, 131.0, 130.0, 129.9, 127.7, 121.8, 115.7, 60.8, 60.6, 21.3, 20.3, 14.2; HRMS (ESI) m/z [M + Na]+ calcd for C16H17NO4Na 310.1055, found 310.1058. Diethyl 3,3′-(2-(acetoxy(cyano)methyl)-4-methyl-1,3phenylene)(2E,2′E)-diacrylate (3j′): yield (28.9 mg, 15%) as a yellow solid; mp 89−90 °C; 1H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 15.6 Hz, 1H), 7.88 (d, J = 16.3 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 6.75 (s, 1H), 6.36 (d, J = 15.6 Hz, 1H), 6.03 (d, J = 16.3 Hz, 1H), 4.34−4.26 (m, 4H), 2.32 (s, 3H), 2.13 (s, 3H), 1.36 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 168.2, 166.1, 165.2, 141.2, 8268

DOI: 10.1021/acs.joc.8b00991 J. Org. Chem. 2018, 83, 8265−8271

Article

The Journal of Organic Chemistry

C13H13NO2Na 238.0844, found 238.0848. A mixture of meta- and para-olef inated products, meta/para = 40:20: 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 16.0 Hz, 1H), 7.53 (t, J = 9.1 Hz, 1H), 7.48 (s, 1H), 7.44−7.37 (m, 1H), 7.37−7.31 (m, 1H), 6.47 (d, J = 16.0 Hz, 0.6H), 6.45 (d, J = 16.0 Hz, 0.4H), 4.27 (q, J = 7.1 Hz, 2H), 3.78 (s, 2H), 1.34 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 166.7, 166.7, 143.4, 143.4, 135.5, 134.4, 131.8, 130.7, 129.7, 129.5, 128.7, 128.5, 127.7, 127.4, 119.5, 119.2, 117.43, 117.4, 60.7, 60.6, 23.5, 14.3; HRMS (ESI) m/z [M + Na]+ calcd for C13H13NO2Na 238.0844, found 238.0845. Methyl (E)-3-(2-(acetoxy(cyano)methyl)-3-methylphenyl)acrylate (4a): yield (94.3 mg, 69%) as a yellow oil; 1H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 15.7 Hz, 1H), 7.42 (d, J = 7.6 Hz, 1H), 7.36 (t, J = 7.7 Hz, 1H), 7.30−7.26 (m, 1H), 6.87 (s, 1H), 6.33 (d, J = 15.6 Hz, 1H), 3.83 (s, 3H), 2.58 (s, 3H), 2.15 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.6, 166.5, 141.5, 138.3, 135.6, 132.9, 130.7, 128.6, 126.3, 122.6, 115.6, 57.9, 51.9, 20.3, 20.0; HRMS (ESI) m/z [M + Na]+ calcd for C15H15NO4Na 296.0899, found 296.0900. Butyl (E)-3-(2-(acetoxy(cyano)methyl)-3-methylphenyl)acrylate (4b): yield (104.1 mg, 66%) as a yellow oil; 1H NMR (400 MHz, CDCl3) δ 8.26 (d, J = 15.6 Hz, 1H), 7.44 (d, J = 7.6 Hz, 1H), 7.35 (t, J = 7.7 Hz, 1H), 7.27 (d, J = 7.8 Hz, 1H), 6.87 (s, 1H), 6.34 (d, J = 15.6 Hz, 1H), 4.24 (t, J = 6.6 Hz, 2H), 2.58 (s, 3H), 2.15 (s, 3H), 1.76−1.66 (m, 2H), 1.46 (tq, J = 14.6, 7.3 Hz, 2H), 0.97 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 168.5, 166.1, 141.2, 138.3, 135.6, 132.8, 130.6, 128.6, 126.2, 123.0, 115.6, 64.6, 57.9, 30.7, 20.3, 20.0, 19.2, 13.7; HRMS (ESI) m/z [M + Na]+ calcd for C18H21NO4Na 338.1368, found 338.1370. (E)-Cyano(2-methyl-6-(3-oxopent-1-en-1-yl)phenyl)methyl acetate (4c): yield (65.1 mg, 48%) as a yellow oil; 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 15.9 Hz, 1H), 7.46 (d, J = 7.6 Hz, 1H), 7.37 (t, J = 7.7 Hz, 1H), 7.28 (d, J = 8.0 Hz, 1H), 6.90 (s, 1H), 6.60 (d, J = 15.9 Hz, 1H), 2.77 (q, J = 7.3 Hz, 2H), 2.58 (s, 3H), 2.16 (s, 3H), 1.20 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 200.6, 168.5, 139.0, 138.3, 135.9, 132.9, 130.7, 130.7, 128.8, 126.2, 115.7, 57.9, 33.6, 20.3, 20.0, 8.1; HRMS (ESI) m/z [M + Na]+ calcd for C16H17NO3Na 294.1106, found 294.1105. (E)-Cyano(2-methyl-6-(2-(phenylsulfonyl)vinyl)phenyl)methyl acetate (4d): yield (76.4 mg, 43%) as a foamy yellow solid: 1H NMR (400 MHz, chloroform-d) δ 8.30 (d, J = 15.1 Hz, 1H), 8.04−8.00 (m, 2H), 7.66−7.61 (m, 1H), 7.59−7.54 (m, 2H), 7.39−7.27 (m, 3H), 6.85 (s, 1H), 6.81 (d, J = 15.1 Hz, 1H), 2.55 (s, 3H), 2.16 (s, 3H); 13 C NMR (101 MHz, chloroform-d) δ 168.5, 139.9, 139.4, 138.3, 133.7, 133.6, 131.7, 130.8, 129.4, 129.2, 128.0, 127.7, 126.7, 115.6, 57.7, 20.4, 20.0; HRMS (ESI) m/z [M + H]+ calcd for C19H18NO4S 356.0956, found 356.0952. (E)-Cyano(2-methyl-6-(3-oxoprop-1-en-1-yl)phenyl)methyl acetate (4e): yield (13.4 mg, 11%) as a yellow solid; mp 75−76 °C; 1 H NMR (400 MHz, CDCl3) δ 9.81 (d, J = 7.7 Hz, 1H), 8.12 (d, J = 15.6 Hz, 1H), 7.50 (d, J = 7.6 Hz, 1H), 7.41 (t, J = 7.7 Hz, 1H), 7.34 (d, J = 7.4 Hz, 1H), 6.94 (s, 1H), 6.65 (dd, J = 15.6, 7.7 Hz, 1H), 2.60 (s, 3H), 2.16 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 193.3, 168.5, 148.8, 138.5, 134.9, 133.7, 132.3, 130.9, 128.9, 126.4, 115.6, 57.7, 20.35, 20.0; HRMS (ESI) m/z [M + Na]+ calcd for C14H13NO3Na 266.0793, found 266.0793. General Procedure for the Synthesis of Product 5a.16 To a solution of 3b (92.3 mg, 0.3 mmol) in ethanol (1.5 mL) was added ptoluenesulfonic acid monohydrate (57.1 mg, 0.3 mmol), and the mixture was stirred at room temperature for 2 days. The solvent was evaporated in vacuo, and the residue was purified by column chromatography on silica gel, eluting with EtOAc/hexane (20%−30% gradient) to afford the desired product 5a. Ethyl (E)-3-(3-chloro-2-(cyano(hydroxy)methyl)phenyl)acrylate (5a): yield (68.5 mg, 86%) as a yellow oil; 1H NMR (400 MHz, chloroform-d) δ 8.33 (d, J = 15.8 Hz, 1H), 7.51 (dd, J = 7.9, 1.3 Hz, 1H), 7.46 (dd, J = 8.1, 1.4 Hz, 1H), 7.41−7.34 (m, 1H), 6.37 (d, J = 15.8 Hz, 1H), 6.28 (s, 1H), 4.29 (q, J = 7.2 Hz, 2H), 4.18 (s, 1H), 1.35 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, chloroform-d) δ 166.5, 140.8, 137.1, 134.2, 131.2, 131.0, 127.1, 123.4, 117.7, 61.2, 58.7, 14.2;

140.7, 138.9, 136.6, 133.4, 132.4, 128.04, 128.0, 127.8, 122.2, 115.5, 61.1, 60.8, 58.9, 20.8, 20.3, 14.3, 14.2; HRMS (ESI) m/z [M + Na]+ calcd for C21H23NO6Na 408.1423, found 408.1432. Ethyl (E)-3-(2-(acetoxy(cyano)methyl)-5-methylphenyl)acrylate (3k): yield (28.7 mg, 20%) as a yellow solid; mp 62−63 °C; 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 15.7 Hz, 1H), 7.56 (d, J = 7.9 Hz, 1H), 7.45−7.42 (m, 1H), 7.31−7.27 (m, 1H), 6.57 (s, 1H), 6.38 (d, J = 15.7 Hz, 1H), 4.28 (q, J = 7.1 Hz, 2H), 2.40 (s, 3H), 2.16 (s, 3H), 1.34 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 168.7, 166.0, 141.2, 139.4, 133.8, 131.1, 129.3, 128.4, 127.4, 122.7, 115.8, 60.8, 60.5, 21.2, 20.3, 14.2; HRMS (ESI) m/z [M + Na]+ calcd for C16H17NO4Na 310.1055, found 310.1057. Diethyl 3,3′-(2-(acetoxy(cyano)methyl)-5-methyl-1,3phenylene)(2E,2′E)-diacrylate (3k′): yield (104.1 mg, 54%) as a yellow solid; mp 91−92 °C; 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 15.7 Hz, 2H), 7.40 (s, 2H), 6.81 (s, 1H), 6.35 (d, J = 15.6 Hz, 2H), 4.30 (q, J = 7.1 Hz, 4H), 2.41 (s, 3H), 2.15 (s, 3H), 1.36 (t, J = 7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 168.4, 165.8, 141.3, 140.5, 136.0, 130.1, 125.8, 124.0, 115.3, 60.9, 57.7, 21.2, 20.3, 14.3; HRMS (ESI) m/z [M + Na]+ calcd for C21H23NO6Na 408.1423, found 408.1424. Ethyl (E)-3-(2-(acetoxy(cyano)methyl)-5-chlorophenyl)acrylate (3l): yield (73.9 mg, 48%) as a yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 15.7 Hz, 1H), 7.64−7.59 (m, 2H), 7.45 (dd, J = 8.3, 2.2 Hz, 1H), 6.56 (s, 1H), 6.40 (d, J = 15.7 Hz, 1H), 4.29 (q, J = 7.1 Hz, 2H), 2.17 (s, 3H), 1.35 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 168.5, 165.5, 137.9, 137.1, 135.7, 130.6, 130.3, 128.6, 127.8, 124.3, 115.3, 61.0, 60.1, 20.29, 14.2; HRMS (ESI) m/z [M + Na]+ calcd for C15H14ClNO4Na 330.0509, found 330.0506. Diethyl 3,3′-(2-(acetoxy(cyano)methyl)-5-chloro-1,3-phenylene)(2E,2′E)-diacrylate (3l′): yield (54.8 mg, 27%) as a yellow solid; mp 76−77 °C; 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 15.6 Hz, 2H), 7.56 (s, 2H), 6.79 (s, 1H), 6.37 (d, J = 15.6 Hz, 2H), 4.31 (q, J = 7.1 Hz, 4H), 2.16 (s, 3H), 1.36 (t, J = 7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 168.3, 165.4, 139.1, 137.9, 137.3, 129.1, 126.9, 125.4, 114.8, 61.1, 57.4, 20.3, 14.2; HRMS (ESI) m/z [M + Na]+ calcd for C20H20ClNO6Na 428.0877, found 428.0876. Ethyl (E)-3-(2-(acetoxy(cyano)methyl)-6-fluoro-3-methylphenyl)acrylate (3m): yield (87.0 mg, 57%) as a yellow solid; mp 77−78 °C; 1 H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 16.1 Hz, 1H), 7.30−7.19 (m, 1H), 7.13 (t, J = 9.2 Hz, 1H), 6.80 (s, 1H), 6.43 (d, J = 16.2 Hz, 1H), 4.30 (q, J = 7.1 Hz, 2H), 2.55 (s, 3H), 2.16 (s, 3H), 1.36 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 168.4, 165.9, 159.3 (d, JC−F = 251.3 Hz), 134.5, 134.1 (d, JC−F = 3.7 Hz), 133.3 (d, JC−F = 8.8 Hz), 129.9, 127.5 (d, JC−F = 9.6 Hz), 123.6 (d, JC−F = 13.8 Hz), 118.0 (d, JC−F = 23.0 Hz), 115.2, 60.9, 58.1 (d, JC−F = 3.0 Hz), 20.3, 19.6, 14.26; HRMS (ESI) m/z [M + Na]+ calcd for C16H16FNO4Na 328.0961, found 328.0965. 3n (a mixture of ortho-, meta-, and para-olefinated products o/ (m + p) = 50:50): yield (45.3 mg, 26%) as a yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 15.8 Hz, 0.5H), 7.68 (d, J = 16.0 Hz, 0.3H), 7.68 (d, J = 16.0 Hz, 0.2H), 7.64−7.57 (m, 0.5H), 7.55−7.46 (m, 1H), 7.44−7.31 (m, 2.5H), 6.46 (d, J = 16.0 Hz, 0.3H), 6.44 (d, J = 16.1 Hz, 0.2H), 6.40 (d, J = 15.8 Hz, 0.5H), 5.24 (s, 1H), 5.12 (s, 1H), 4.35−4.23 (m, 2H), 2.16−2.06 (m, 3H), 1.38−1.32 (m, 3H); 13 C NMR (101 MHz, CDCl3) δ 170.8, 170.7, 166.9, 166.9, 166.6, 166.6, 144.0, 143.9, 141.0, 138.1, 136.8, 134.9, 134.7, 134.4, 134.0, 130.2, 130.0, 129.9, 129.1, 129.0, 128.6, 128.2, 127.8, 127.7, 126.9, 120.9, 118.9, 118.7, 65.8, 65.7, 63.9, 60.6, 60.6, 21.0, 20.9, 14.3; HRMS (ESI) m/z [M + Na]+ calcd for C14H16O4Na 271.0946, found 271.0948. 3o (a mixture of ortho-, meta-, and para-olefinated products o/ (m+p) = 40:60): yield (58.1 mg, 54%) as a yellow oil. Ethyl (E)-3-(2(cyanomethyl)phenyl)acrylate (ortho-olef inated product): 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 15.7 Hz, 1H), 7.60 (dd, J = 7.5, 1.3 Hz, 1H), 7.50 (d, J = 7.3 Hz, 1H), 7.42 (td, J = 7.5, 1.6 Hz, 1H), 7.40−7.35 (m, 1H), 6.40 (d, J = 15.7 Hz, 1H), 4.28 (q, J = 7.1 Hz, 2H), 3.86 (s, 2H), 1.35 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 166.3, 139.7, 133.3, 130.6, 129.3, 128.9, 128.8, 127.4, 122.1, 117.1, 60.8, 21.7, 14.3; HRMS (ESI) m/z [M + Na]+ calcd for 8269

DOI: 10.1021/acs.joc.8b00991 J. Org. Chem. 2018, 83, 8265−8271

Article

The Journal of Organic Chemistry HRMS (ESI) m/z [M + Na]+ calcd for C13H12ClNO3Na 288.0403, found 288.0405. Synthesis of Product 5b. Ethyl (E)-3-(2-(1-Acetoxy-2-(tertbutylamino)-2-oxoethyl)-3-chlorophenyl)acrylate (5b). Product 5b was synthesized according to the reported method.17 20% EtOAc/ hexane as an elution gradient to yield 5b (112.3 mg, 98%) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 15.7 Hz, 1H), 7.42 (dd, J = 7.9, 4.1 Hz, 2H), 7.30−7.24 (m, 1H), 6.73 (s, 1H), 6.29 (d, J = 15.7 Hz, 1H), 6.18 (s, 1H), 4.34−4.21 (m, 2H), 2.16−2.10 (m, 3H), 1.38 (s, 9H), 1.36−1.31 (m, 3H); 13C NMR (101 MHz, CDCl3) δ 168.6, 166.3, 166.1, 142.0, 137.2, 136.0, 132.9, 131.1, 130.0, 126.4, 122.2, 71.3, 60.6, 51.9, 28.4, 20.8, 14.3; HRMS (ESI) m/z [M + Na]+ calcd for C19H24ClNO5Na 404.1241, found 404.1243.

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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.8b00991. 1 H and 13C NMR spectra for all compounds (PDF)

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AUTHOR INFORMATION

Corresponding Authors

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

Yun-He Xu: 0000-0001-8817-0626 Teck-Peng Loh: 0000-0002-2936-337X Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We gratefully acknowledge the funding support of the National Natural Science Foundation of China (21672198), the State Key Program of National Natural Science Foundation of China (21432009), the Fundamental Research Funds for the Central Universities (WK2060190082), and the Collaborative Innovation Center of Chemistry for Energy Materials (2011-iChEM) for financial support.

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REFERENCES

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DOI: 10.1021/acs.joc.8b00991 J. Org. Chem. 2018, 83, 8265−8271

Article

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DOI: 10.1021/acs.joc.8b00991 J. Org. Chem. 2018, 83, 8265−8271