(3 + 3) Annulation of Nitroallylic Acetates with Stabilized Sulfur Ylides

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(3 + 3) Annulation of Nitroallylic Acetates with Stabilized Sulfur Ylides for the Synthesis of 2‑Aryl Terephthalates Lakshminarayana Satham and Irishi N. N. Namboothiri* Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400 076, India

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ABSTRACT: A novel (3 + 3) annulation approach has been developed for the synthesis of 2-aryl terephthalates from nitroallylic acetates and stabilized sulfur ylides. The 2-aryl terephthalates, which are also biaryls bearing a terephthalate moiety, are formed through a cascade of reactions such as a γ-selective SN2′ reaction, γ-selective intramolecular Michael addition, and two eliminations in the presence of Cs2CO3 in CH3CN at room temperature. The products are formal precursors of farnesyltransferase inhibitors and are also potential monomers in polymer chemistry.

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molecules, and functional materials.5 Such aromatics are conventionally synthesized via functional group modification on benzene skeleton involving diverse aromatic substitution and coupling strategies.6 These approaches, though widely employed, require precise positioning of appropriate functional groups or directing groups. Alternatively, different annulation modes are available in the synthetic chemist’s arsenal for the construction of an aromatic ring under a variety of metalcatalyzed and metal-free conditions.7 Among various annulation approaches, (3 + 3) annulation is an efficient cascade strategy for the quick construction of sixmembered carbo- and heterocycles from open chain compounds in a highly regioselective manner.8−10 Although, there are several reports on the synthesis of 2-aryl terephthalates by conventional modification of benzene skeleton and functional group interconversion (Scheme 1a− c),11 to the best of our knowledge, there are no reports on the synthesis of 2-aryl terepthalates via a (3 + 3) annulation. In recent years, the Morita−Baylis−Hillman and Rauhut− Currier adducts of nitroalkenes have been extensively exploited by us and others for the synthesis of numerous multifunctional and bioactive molecules via various annulation strategies.12 In particular, nitroallylic acetates/bromides emerged as efficient bielectrophilic 2/3-carbon components for the synthesis of various carbocycles and heterocycles via cascade SN2′ reaction−intramolecular 5-exo-trig or 6-endo-trig cyclization (Scheme 1d).10,13,14 While 6-endo-trig is the only cyclization pathway for the primary nitroallylic acetates/bromides (E = H),10,14 both 5-exo-trig and 6-endo-trig are in principle possible for the secondary nitroallylic acetates (E = CO2Et) in their reaction with various binucleophiles.10,13 In this context, synthesis of unsymmetrical terephthalates bearing a key aryl

arnesyltransferase (FTase) is a potential target for the treatment of cancer, malaria, and many other diseases due to its ability to activate the disease causing Ras protein, via post-translational farnesylation.1 Development of inhibitors of FTase is therefore an attractive objective.2 2-Aryl terephthalates (biaryl-1,4-diesters) are common precursors for many FTase inhibitors (Figure 1).3 Terephthalates are also key monomers in the synthesis of a wide variety of polymers and other materials.4 Functionalized aromatics, to which terephthalates belong, in general, are attractive building blocks in organic synthesis and are also integral parts of numerous natural products, bioactive

Figure 1. 2-Aryl terephthalates-formal synthons of farnesyltransferase (FTase) inhibitors (anticancer agents).3 © 2018 American Chemical Society

Received: May 8, 2018 Published: July 3, 2018 9471

DOI: 10.1021/acs.joc.8b00917 J. Org. Chem. 2018, 83, 9471−9477

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The Journal of Organic Chemistry

(2.0 equiv) in CH3CN (3 mL) led to complete consumption of the starting materials in 1 h to afford the product 2-aryl terephthalate 3a in 56% yield (entry 1). Lowering or increasing the base loading (1 or 3 equiv) or changing the ratio of 2a and 1a (1:1 or 1:1.5) provided inferior results. Further changing the base to K2CO3, NaOH, or an amine base such as DBU resulted in longer reaction times and lower yields (entries 2− 4). Attempts to further improve the yield by screening other polar aprotic solvents such as THF, DMF, and acetone as well as a nonpolar solvent such as toluene proved futile (entries 5− 8). Subsequently, in order to minimize self-dimerization/ oligomerization/polymerization, sulfonium bromide 1a in CH3CN (1 mL) was added dropwise to a mixture of nitroallylic acetate 2a and Cs2CO3 (2.0 equiv) in CH3CN (2 mL) which furnished the product 3a in 57% yield in 15 min (entry 9), although performing this reaction at lower temperature (0 °C) did not lead to better results. Under the above optimized conditions (Table 1), we proceeded to investigate the substrate scope for the synthesis of substituted 2-aryl terephthalates 3 (Scheme 2). Thus, nitroallylic acetates 2d−2f, besides model substrate 2a, bearing strongly electron-donating aryl groups afforded the desired products 3a and 3d−3f in moderate yield (49−57%). Product 3b possessing the parent phenyl group and 3c with a weakly electron donating aryl group were also formed in respectable yields (43−46%). Lower yields were encountered in the case of terephthalates 3g−3h with weakly deactivating halogens (31− 41%), but pleasingly, terephthalate 3i containing a strongly deactivated aryl group was formed in good yield (55%). Terephthalates having heteroaryl groups 3j and 3k and a styrenyl group 3l were formed in moderate yields (32−41%). However, a fused aryl (naphthyl) containing terephthalate 3m was formed in good yield (52%). Attempted transformation of a β-alkyl bearing nitroallylic acetate 2n to the corresponding terephthalate 3n met with failure as a complex mixture was isolated. Having synthesized terephthalates 3a−m, decorated with two different ester groups and an aryl group, using a methyl ester bearing sulfonium bromide 1a, we employed sulfonium bromides 1b−c equipped with ethyl ester and cyano groups. Thus, terephthalate 3o bearing identical ester groups and an electron-rich aryl group was formed in 51% yield. Similarly, cyano group containing biaryls 3p and 3q were formed in very good yield (58−65%). The structure and regiochemistry of 2-aryl terephthalates 3 were determined by detailed analysis of their spectral data. In particular, 1H NMR analysis of a representative compound 3j with the help of the 1H−1H COSY spectrum showed strong coupling (ortho, J = 8.0 Hz) between two aryl protons which were assigned H1 and H2. The absence of further coupling for H1 and the presence of an additional weak meta-coupling (J = 1.6 Hz) for H2 (with H3) confirmed this assignment. The regiochemistry was further confirmed by 1H−1H NOESY analysis which showed the key NOE interaction between H3 and the furyl proton and no NOE interaction between the two ester alkyl groups. Finally, the structure and regiochemistry were unambiguously established by single crystal X-ray analysis (Figure 2). A plausible mechanism for the formation of 2-aryl terephthalate 3 via a (3 + 3) annulation is depicted in Scheme 3. Deprotonation of sulfonium bromide 1 results in a stabilized sulfur ylide I whose more probable γ-selective addition to nitroallylic acetate 2 via soft−soft interaction in an SN2′

Scheme 1. Approaches to 2-Aryl Terephthalates and Bielectrophilic Reactivity of Nitroallylic Acetate/Bromide

group and two different ester groups (biaryl-1,4-diesters) from nitroallylic acetates as the bielectrophiles and sulfonium ylides as the binucleophiles appeared appealing (Scheme 1e). A crotonate derived sulfonium bromide was identified as the key precursor to the sulfur ylide.15 As part of the optimization studies, nitroallylic acetate 2a was treated with sulfonium bromide 1a in the presence of different bases and solvents at room temperature (Table 1). At first, treatment of a 1:1.2 mixture of 2a and 1a with Cs2CO3 Table 1. Optimization of Reaction Conditions

entry

base

solvent

time/h

yield/%a

1 2 3 4 5 6 7 8 9 10

Cs2CO3 K2CO3 NaOH DBU Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3 Cs2CO3

CH3CN CH3CN CH3CN CH3CN THF DMF Acetone Toluene CH3CN CH3CN

1 24 1.5 20 24 10 min 3 30 15 min 7

56 46 50 26 44 −b −c 40 57d 45d,e

a

After silica-gel column chromatography. bComplex mixture. cTraces. Dropwise addition of sulfonium bromide 1a in CH3CN (1 mL). eAt 0 °C. d

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DOI: 10.1021/acs.joc.8b00917 J. Org. Chem. 2018, 83, 9471−9477

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The Journal of Organic Chemistry Scheme 2. Scope of the (3 + 3) Annulation for One-Pot Synthesis of 2-Aryl Terephthalatesa

Scheme 3. Plausible Reaction Mechanism

SN2 reaction involving α-selective addition of ylide I to nitroallylic acetate 2 via hard−hard interaction appeared less probable due to the tertiary nature of the electrophilic center bearing the acetate group and mild basic conditions. In conclusion, terephthalates bearing two different ester groups and an aryl group at position 2 (biaryl-1,4-diesters) have been synthesized in moderate to good yield through a novel (3 + 3) annulation of nitroallylic acetates with a crotonate derived sulfonium ylide. This annulation, involving a γ-selective SN2′ reaction and a γ-selective intramolecular Michael addition, is highly regioselective and offers formal precursors to farnesyltransferase inhibitors.16 General Experimental Details. The reagents and solvents were purchased from commercial sources and were used as received unless mentioned otherwise. The reactions were monitored by TLC. The melting points recorded are uncorrected. NMR spectra (1H, 1H decoupled 13C, 1H−1H COSY, and 1H−1H NOESY) were recorded with tetramethylsilane (TMS) as the internal standard. The coupling constants (J values) are given in Hz. High resolution mass spectra were recorded under ESI Q-TOF conditions. X-ray data were collected on a diffractometer equipped with graphite monochromated Mo Kα radiation. The structure was solved by direct methods shelxs97 and refined by full-matrix least-squares against F2 using shelxl97 software. Sulfonium bromides 115 and nitroallylic acetates 217 were prepared by literature methods. General Procedure for the Synthesis of 2-Aryl Terephthalates 3. To a stirred solution of MBH-acetate 2 (0.3 mmol, 1.0 equiv) in acetonitrile (2.0 mL) at rt were added Cs 2 CO 3 (0.6 mmol, 2.0 equiv) in one portion and subsequently sulfonium bromide 1 (0.36 mmol, 1.2 equiv) dropwise in acetonitrile (1.0 mL). Progress of the reaction was monitored by TLC analysis. After completion of reaction, the solvent was evaporated under reduced pressure, and the residue was treated with water (5 mL). The aqueous layer was extracted with ethyl acetate (3 × 5 mL). The combined organic layer was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography by eluting with 5−20% EtOAc−pet. ether (gradient elution) to afford pure product 3. 5-Ethyl 2-Methyl 4′-Methoxy-[1,1′-biphenyl]-2,5-dicarboxylate (3a). Pale yellow liquid; yield 51 mg, 57%; IR (neat, cm−1) 1724 (vs), 1610 (m); 1H NMR (CDCl3, 400 MHz) δ 1.33 (t, J = 7.2 Hz, 3H), 3.61 (s, 3H), 3.78 (s, 3H),

a

Yields after silica-gel column chromatography. No characterizable side products were observed in these reactions.

Figure 2. NMR analysis of 3j and X-ray structure of analog 3i.

fashion generates intermediate II. A second γ-selective Michael addition, this time in an intramolecular 6-endo-trig fashion, provides intermediate III, which upon two consecutive eliminations, namely of Me 2 S and HNO 2 , results in terephthalate 3. Formation of the same product via an initial 9473

DOI: 10.1021/acs.joc.8b00917 J. Org. Chem. 2018, 83, 9471−9477

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The Journal of Organic Chemistry

3.69 (s, 3H), 4.40 (q, J = 7.1 Hz, 2H), 7.20 (d, J = 8.2 Hz, 2H), 7.54 (d, J = 8.2 Hz, 2H), 7.88 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 0.8 Hz, 1H), 8.08 (dd, J = 8.1, 0.8 Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ 14.5, 52.5, 61.7, 122.2, 128.6, 130.1, 130.2, 131.5, 131.7, 133.2, 134.5, 139.5, 141.5, 165.7, 168.3; MS (ES+, Ar) m/z HRMS calcd for C17H1579BrNaO4 (MNa+, 100) 385.0046, found 385.0052. 5-Ethyl 2-Methyl 4′-Fluoro-[1,1′-biphenyl]-2,5-dicarboxylate (3h). White solid; yield 28 mg, 31%; mp 76−78 °C; IR (neat, cm−1) 1725 (vs), 1607 (s); 1H NMR (CDCl3, 400 MHz) δ 1.40 (t, J = 7.1 Hz, 3H), 3.68 (s, 3H), 4.41 (q, J = 7.1 Hz, 2H), 7.10 (t, J = 8.6 Hz, 2H), 7.29 (d, J = 8.6, 5.3 Hz, 2H), 7.86 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 1.6 Hz, 1H), 8.07 (dd, J = 8.0, 1.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 14.5, 52.4, 61.7, 115.4 (d, JC−F = 21.7 Hz), 128.4, 130.0, 130.2 (d, JC−F = 8.4 Hz), 131.8, 133.1, 134.8, 136.5 (d, JC−F = 3.6 Hz) 141.6, 162.7 (d, JC−F = 246.9 Hz), 165.8, 168.5; 19F NMR (CDCl3, 376 MHz) δ (ppm) −114.7; MS (ES+, Ar) m/z HRMS calcd for C17H15FNaO4 (MNa+, 100) 325.0847, found 325.0846. 5-Ethyl 2-Methyl 2′-Nitro-[1,1′-biphenyl]-2,5-dicarboxylate (3i). White solid; yield 55 mg, 55%; mp 115−117 °C; IR (neat, cm−1) 1722 (vs); 1H NMR (CDCl3, 500 MHz) δ 1.39 (t, J = 7.1 Hz, 3H), 3.68 (s, 3H), 4.40 (q, J = 7.1 Hz, 2H), 7.29 (dd, J = 7.6, 0.9 Hz, 1H), 7.56 (td, J = 7.6, 0.9 Hz, 1H), 7.66 (td, J = 7.6, 0.9 Hz, 1H), 7.90 (d, J = 0.4 Hz, 1H), 8.13− 8.14 (unresolved m, 2H), 8.16 (dd, J = 7.6, 0.9 Hz, 1H); Confirmed by 1H−1H COSY experiment; 13C NMR (CDCl3, 125 MHz) δ 14.4, 52.5, 61.8, 124.4, 128.8, 129.1, 130.7, 131.0, 131.6, 132.4, 133.1, 133.8, 136.6, 140.4, 148.1, 165.5, 166.2; MS (ES+, Ar) m/z HRMS calcd for C17H15NNaO6 (MNa+, 100) 352.0792, found 352.0788. Selected X-ray data: C17H15NO6, M 329.30, triclinic, space group P1̅ , a = 9.6495(3) Å, b = 15.4042(4) Å, c = 15.4078(9) Å, α = 107.095(2)°, β = 99.206(2)°, γ = 98.222(2)°, V = 3092.28(15) Å3, Dc = 1.415 mg/m3, Z = 8, F(000) = 1376, λ = 0.71073 Å, μ = 0.109 mm−1, total/unique reflections = 41061/10826 [R(int) = 0.0327], θ range = 2.18° to 25.00°, Final R [I > 2σ(I)]: R1 = 0.0537, wR2 = 0.1593, R (all data): R1 = 0.0816, wR2 = 0.1930. 4-Ethyl 1-Methyl 2-(Furan-2-yl)terephthalate (3j). Pale yellow liquid; yield 33 mg, 41%; IR (neat, cm−1) 1722 (vs); 1H NMR (CDCl3, 400 MHz) δ 1.41 (t, J = 7.1 Hz, 3H), 3.86 (s, 3H), 4.41 (q, J = 7.1 Hz, 2H), 6.49 (dd, J = 3.4, 1.9 Hz, 1H), 6.66 (d, J = 3.4 Hz, 1H), 7.50 (d, J = 1.9 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.99 (dd, J = 8.0, 1.6 Hz, 1H), 8.28 (d, J = 1.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 14.4, 52.7, 61.6, 108.9, 111.9, 128.4, 129.1, 129.3, 130.0, 132.8, 133.7, 143.3, 151.6, 165.7, 169.2; MS (ES+, Ar) m/z HRMS calcd for C15H14NaO5 (MNa+, 100) 297.0733, found 297.0740. Confirmed by 1 H−1H COSY and NOESY experiments. 4-Ethyl 1-Methyl 2-(Thiophen-2-yl)terephthalate (3k). Pale yellow liquid; yield 31 mg, 36%; IR (neat, cm−1) 1724 (vs); 1H NMR (CDCl3, 500 MHz) δ 1.41 (t, J = 7.1 Hz, 3H), 3.76 (s, 3H), 4.41 (q, J = 7.1 Hz, 2H), 7.07−7.09 (m, 2H), 7.38 (dd, J = 3.9, 2.2 Hz, 1H), 7.75 (d, J = 8.1 Hz, 1H), 8.04 (dd, J = 8.1, 1.3 Hz, 1H), 8.15 (d, J = 1.3 Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ 14.5, 52.7, 61.7, 126.6, 127.0, 127.6, 128.8, 129.5, 132.2, 132.8, 134.4, 135.7, 141.1, 165.7, 168.8; MS (ES+, Ar) m/z HRMS calcd for C15H14NaO4S (MNa+, 100) 313.0505, found 313.0507. 4-Ethyl 1-Methyl (E)-2-Styrylterephthalate (3l). Light yellow solid; yield 30 mg, 32%; mp 83−85 °C; IR (neat, cm−1) 1722 (vs); 1H NMR (CDCl3, 500 MHz) δ 1.44 (t, J =

4.33 (q, J = 7.2 Hz, 2H), 6.94 (d, J = 8.7 Hz, 2H), 7.25 (d, J = 8.7 Hz, 2H), 7.79 (d, J = 7.9 Hz, 1H), 8.03 (dd, J = 7.9, 1.7 Hz, 1H), 8.05 (d, J = 1.7 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 14.4, 52.4, 55.4, 61.6, 113.9, 127.9, 129.6, 129.8, 131.8, 132.7, 132.8, 134.9, 142.1, 159.4, 165.9, 169.0; MS (ES+, Ar) m/z HRMS calcd for C18H18NaO5 (MNa+, 100) 337.1046, found 337.1047. 5-Ethyl 2-Methyl[1,1′-biphenyl]-2,5-dicarboxylate (3b). Pale yellow liquid; yield 37 mg, 43%; IR (neat, cm−1) 1724 (vs); 1H NMR (CDCl3, 500 MHz) δ 1.41 (t, J = 7.1 Hz, 3H), 3.65 (s, 3H), 4.41 (q, J = 7.1 Hz, 2H), 7.32−7.35 (m, 2H), 7.36−7.44 (m, 3H), 7.85 (d, J = 8.5 Hz, 1H), 8.05−8.08 (m, 2H); 13C NMR (CDCl3, 125 MHz) δ 14.5, 52.4, 61.6, 127.8, 128.3, 128.4, 128.5, 129.9, 131.8, 133.0, 134.9, 140.5, 142.6, 165.9, 168.8; MS (ES+, Ar) m/z HRMS calcd for C17H16NaO4 (MNa+, 100) 307.0941, found 307.0943. 5-Ethyl 2-Methyl 4′-Methyl-[1,1′-biphenyl]-2,5-dicarboxylate (3c). Pale yellow liquid; yield 41 mg, 46%; IR (neat, cm−1) 1720 (vs); 1H NMR (CDCl3, 500 MHz) δ 1.40 (t, J = 7.2 Hz, 3H), 2.40 (s, 3H), 3.69 (s, 3H), 4.40 (q, J = 7.2 Hz, 2H), 7.22−7.24 (unresolved m, 4H), 7.83 (dd, J = 7.9, 0.6 Hz, 1H), 8.04 (dd, J = 7.9, 1.7 Hz, 1H), 8.06 (d, J = 1.7 Hz, 1H); 13 C NMR (CDCl3, 125 MHz) δ 14.4, 21.4, 52.4, 61.6, 128.0, 128.3, 129.1, 129.8, 131.8, 132.8, 134.9, 137.5, 137.6, 142.5, 165.9, 168.9; MS (ES+, Ar) m/z HRMS calcd for C18H18NaO4 (MNa+, 100) 321.1097, found 321.1099. 5-Ethyl 2-Methyl 3′-Methoxy-[1,1′-biphenyl]-2,5-dicarboxylate (3d). Pale yellow liquid; yield 49 mg, 52%; IR (neat, cm−1) 1724 (vs), 1601 (s); 1H NMR (CDCl3, 400 MHz) δ 1.40 (t, J = 7.1 Hz, 3H), 3.67 (s, 3H), 3.83 (s, 3H), 4.40 (q, J = 7.1 Hz, 2H), 6.88−6.94 (m, 3H), 7.31 (t, J = 7.9 Hz, 1H), 7.82 (d, J = 8.5 Hz, 1H), 8.06 (dd, J = 8.5, 1.7 Hz, 1H), 8.07 (d, J = 1.7 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 14.5, 52.4, 55.5, 61.6, 113.4, 114.0, 121.0, 128.4, 129.4, 129.7, 131.7, 132.9, 135.1, 141.8, 142.3, 159.6, 165.9, 168.8; MS (ES+, Ar) m/z HRMS calcd for C18H18NaO5 (MNa+, 100) 337.1046, found 337.1048. 5-Ethyl 2-Methyl 2′,4′-Dimethoxy-[1,1′-biphenyl]-2,5-dicarboxylate (3e). Yellow viscous liquid; yield 50 mg, 49%; IR (neat, cm−1) 1726 (vs), 1611 (vs); 1H NMR (CDCl3, 400 MHz) δ 1.38 (t, J = 7.2 Hz, 3H), 3.69 (s, 6H), 3.85 (s, 3H), 4.39 (q, J = 7.2 Hz, 2H), 6.48 (d, J = 2.3 Hz, 1H), 6.59 (dd, J = 8.3, 2.3 Hz, 1H), 7.22 (d, J = 8.3 Hz, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.99 (d, J = 1.7 Hz, 1H), 8.01 (dd, J = 7.9, 1.7 Hz, 1H); 13 C NMR (CDCl3, 100 MHz) δ 14.4, 52.0, 55.3, 55.5, 61.4, 98.4, 104.6, 122.5, 127.8, 129.4, 130.6, 132.6, 133.1, 135.7, 138.7, 157.1, 161.0, 166.0, 168.4; MS (ES+, Ar) m/z HRMS calcd for C19H20NaO 6 (MNa +, 100) 367.1152, found 367.1160. 5-Ethyl 2-Methyl 3′,4′-Dimethoxy-[1,1′-biphenyl]-2,5-dicarboxylate (3f). Yellow viscous liquid; yield 50 mg, 49%; IR (neat, cm−1) 1720 (vs); 1H NMR (CDCl3, 400 MHz) δ 1.39 (t, J = 7.1 Hz, 3H), 3.68 (s, 3H), 3.89 (s, 3H), 3.91 (s, 3H), 4.40 (q, J = 7.1 Hz, 2H), 6.86 (s, 1H), 6.89, 6.91 (ABq, J = 8.3 Hz, 2H), 7.78 (d, J = 8.1 Hz, 1H), 8.02 (dd, J = 8.1, 1.3 Hz, 1H), 8.05 (d, J = 1.3 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 14.4, 52.5, 56.0, 56.1, 61.6, 111.1, 111.8, 120.9, 127.9, 129.6, 131.6, 132.8, 133.0, 135.2, 142.0, 148.9, 149.0, 165.9, 169.2; MS (ES+, Ar) m/z HRMS calcd for C19H20NaO6 (MNa+, 100) 367.1152, found 367.1163. 5-Ethyl 2-Methyl 4′-Bromo-[1,1′-biphenyl]-2,5-dicarboxylate (3g). Semisolid; yield 45 mg, 41%; IR (neat, cm−1) 1726 (vs); 1H NMR (CDCl3, 500 MHz) δ 1.40 (t, J = 7.1 Hz, 3H), 9474

DOI: 10.1021/acs.joc.8b00917 J. Org. Chem. 2018, 83, 9471−9477

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7.2 Hz, 3H), 3.95 (s, 3H), 4.44 (q, J = 7.2 Hz, 2H), 7.13 (d, J = 16.2 Hz, 1H), 7.29 (t, J = 7.4 Hz, 1H), 7.38 (t, J = 7.4 Hz, 2H), 7.57 (d, J = 7.4 Hz, 2H), 7.94 (d, J = 16.2 Hz, 1H), 7.95−7.97 (m, 2H), 8.39 (s, 1H); 13C NMR (CDCl3, 125 MHz) δ 14.5, 52.6, 61.7, 126.5, 127.2, 127.8, 128.2, 128.3, 128.9, 130.9, 132.3, 132.8, 133.7, 137.3, 139.4, 166.0, 167.5; MS (ES+, Ar) m/z HRMS calcd for C19H18NaO4 (MNa+, 100) 333.1097, found 333.1098. 4-Ethyl 1-Methyl 2-(Naphthalen-1-yl)terephthalate (3m). Colorless liquid; yield 54 mg, 52%; IR (neat, cm−1) 1721 (vs); 1 H NMR (CDCl3, 500 MHz) δ 1.39 (t, J = 7.2 Hz, 3H), 3.40 (s, 3H), 4.41 (q, J = 7.2 Hz, 2H), 7.36 (d, J = 7.0 Hz, 1H), 7.38−7.41 (m, 1H), 7.45−7.50 (m, 2H), 7.52−7.55 (m, 1H), 7.91 (t, J = 8.5 Hz, 2H), 8.09 (d, J = 8.2 Hz, 1H), 8.12 (d, J = 1.6 Hz, 1H), 8.20 (dd, J = 8.2, 1.6 Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ 14.4, 52.2, 61.6, 125.3, 125.4, 125.9, 126.3, 126.4, 128.1, 128.4, 128.7, 130.2, 132.0, 132.9, 133.3, 133.4, 135.6, 138.7, 141.5, 165.8, 167.5; MS (ES+, Ar) m/z HRMS calcd for C21H18NaO4 (MNa+, 100) 357.1097, found 357.1095. Diethyl 4′-Methoxy-[1,1′-biphenyl]-2,5-dicarboxylate (3o).18 Pale yellow liquid; yield 60 mg, 51%; IR (neat, cm−1) 1722 (vs), 1610 (m); 1H NMR (CDCl3, 400 MHz) δ 1.07 (t, J = 7.1 Hz, 3H), 1.40 (t, J = 7.1 Hz, 3H), 3.84 (s, 3H), 4.14 (q, J = 7.1 Hz, 2H), 4.40 (q, J = 7.1 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 8.8 Hz, 2H), 7.81 (dd, J = 7.7, 0.9 Hz, 1H), 8.03 (dd, J = 7.7, 1.7 Hz, 1H), 8.04 (dd, J = 1.7, 0.9 Hz, 1H); 13 C NMR (CDCl3, 125 MHz) δ 14.0, 14.5, 55.5, 61.5, 61.6, 113.9, 127.9, 129.7 (× 2), 131.8, 132.7, 133.0, 135.5, 142.1, 159.5, 166.0, 168.7; MS (ES+, Ar) m/z HRMS calcd for C19H20NaO5 (MNa+, 100) 351.1203, found 351.1204. Ethyl 6-Cyano-4′-methoxy-[1,1′-biphenyl]-3-carboxylate (3p). White crystalline solid; yield 55 mg, 65%; mp 99−101 °C; IR (neat, cm−1) 2236 (w), 1719 (vs); 1H NMR (CDCl3, 500 MHz) δ 1.41 (t, J = 7.2 Hz, 3H), 3.88 (s, 3H), 4.42 (q, J = 7.2 Hz, 2H), 7.04 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 8.8 Hz, 2H), 7.81 (d, J = 8.1 Hz, 1H), 8.04 (dd, J = 8.1, 1.5 Hz, 1H), 8.16 (d, J = 1.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz) δ 14.4, 55.6, 62.0, 114.5, 114.9, 118.5, 127.8, 129.8, 130.2, 130.9, 134.0, 134.4, 145.6, 160.5, 165.3; MS (ES+, Ar) m/z HRMS calcd for C17H15NNaO3 (MNa+, 55) 304.0944, found 304.0947. Ethyl 4-Cyano-3-(naphthalen-1-yl)benzoate (3q).3e Light yellow solid; yield 60 mg, 58%; mp 92−94 °C; IR (neat, cm−1) 2229 (m), 1722 (vs); 1H NMR (CDCl3, 400 MHz, 50 °C) δ 1.40 (t, J = 7.1 Hz, 3H), 4.42 (q, J = 7.2 Hz, 2H), 7.45−7.51 (m, 3H), 7.54 (t, J = 8.2 Hz, 1H), 7.59 (t, J = 8.2 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.95 (d, J = 8.2 Hz, 1H), 7.98 (d, J = 8.2 Hz, 1H), 8.19−8.23 (m, 2H); Confirmed by 1H−1H COSY experiment; 13C NMR (CDCl3, 100 MHz) δ 14.4, 62.0, 117.4, 117.5, 125.1, 125.3, 126.5, 127.0, 127.8, 128.8, 128.9, 129.8, 131.4, 132.4, 133.4, 133.9, 134.1, 135.2, 144.9, 165.2; MS (ES+, Ar) m/z HRMS calcd for C20H15NNaO2 (MNa+, 100) 324.0995, found 324.0995.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Irishi N. N. Namboothiri: 0000-0002-8945-3932 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS I.N.N.N. thanks SERB-DST India (Grant No. EMR/2014/ 000395) for financial assistance, and L.S. thanks CSIR India, for a senior research fellowship. The authors thank Ms. Sreevani and Mr. Madhusudhan, Department of Chemistry, IIT Bombay, for help with X-ray data.

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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.8b00917. Copies of NMR spectra for all the new compounds; Xray data for 3i (PDF) Crystallographic data for 3i (CIF) 9475

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