Synthesis of Allylbenzene Derivatives through sp³ C–H Bond Functionalization of Toluene Derivatives

Abstract

An sp³ C–H bond-transformation reaction of toluene substrates to afford the corresponding allylbenzene derivatives is described. Optimum conditions were identified as involving the use of tetrabutylammonium iodide and tert-butyl hydroperoxide at 80 °C.

Keywords

C–H activation - methylarenes - C–C bond formation - alkyl arylalkenoates - alkynes

• References and Notes

• 1 Godula K. Sames D. Science 2006; 312: 67
• 2 Izawa Y. Pun D. Stahl SS. Science 2011; 333: 209
• 3 Wang D.-H. Engle KM. Shi B.-F. Yu J.-Q. Science 2010; 327: 315
• 4 Ren Z. Mo F. Dong G. J. Am. Chem. Soc. 2012; 134: 16991
• 5 Zhang S.-Y. Zhang F.-M. Tu Y.-Q. Chem. Soc. Rev. 2011; 40: 1937
• 6 Wasa M. Engle KM. Yu J.-Q. J. Am. Chem. Soc. 2009; 131: 9886
• 7 Hartwig JF. J. Am. Chem. Soc. 2016; 138: 2
• 8 Quinn RK. Könst ZA. Michalak SA. Schmidt Y. Szklarski AR. Flores AR. Nam S. Horne DA. Vanderwal CD. Alexanian EJ. J. Am. Chem. Soc. 2016; 138: 696
• 9 Davidson JM. Triggs C. Chem. Ind. (London) 1966; 457
• 10 Bryant DR. McKeon JE. Ream BC. J. Org. Chem. 1968; 33: 4123
• 11 Varma RS. Naicker KP. Green Chem. 1999; 1: 247
• 12 Wang S. Qian Q. Gong H. Org. Lett. 2012; 14: 3352
• 13 Ueda M. Nishimura K. Kashima R. Ryu I. Synlett 2012; 23: 1085
• 14 Dunet G. Knochel P. Synlett 2007; 1383
• 15 Jia C. Piao D. Oyamada J. Lu W. Kitamura T. Fujiwara Y. Science 2000; 287: 1992
• 16 Liu H. Shi G. Pan S. Jiang Y. Zhang Y. Org. Lett. 2013; 15: 4098
• 17 Feng J. Liang S. Chen S.-Y. Zhang J. Fu S.-S. Yua XQ. Adv. Synth. Catal. 2012; 354: 1287
• 18 Sakamoto R. Inada T. Selvakumar S. Moteki SA. Maruoka K. Chem. Commun. (Cambridge) 2016; 52: 3758
• 19 Khalaj M. Ghazanfarpour-Darjani M. RSC Adv. 2015; 5: 80698
• 20 Ghazanfarpour-Darjani M. Babapour-Kooshalshahi M. Mousavi-Safavi SM. Akbari-Neyestani J. Khalaj M. Synlett 2016; 27: 259
• 21 Khalaj M. Ghazanfarpour-Darjani M. Talei Bavil Olyai MR. Faraji Shamami S. J. Sulfur Chem. 2016; 37: 211
• 22 Alkyl Arylalkenoates 3a–l; General Procedure A sample tube was charged with TBAI (74 mg, 20 mol%), 70% aq TBHP (2.0 mmol), and the appropriate alkyne 2 (1.0 mmol), and the mixture was stirred for 15 min at 25 °C. The appropriate toluene derivative 1 (1.5 mL) was added and the mixture was stirred under vacuum at 80 °C for 14 h. The crude mixture was then concentrated in vacuo, and the reaction was quenched by addition of sat. aq Na₂S₂O₃ (3.0 mL). The mixture was extracted with EtOAc (3 × 5 mL), and the combined organic phases were dried (MgSO₄), filtered, and concentrated in vacuo. The crude product was purified by column chromatography [silica gel, hexane–EtOAc (8:1)]. Dimethyl 2-Benzylfumarate (3a) Colorless oil; yield: 0.17 g (84%). IR (KBr): 3035, 2928, 1728, 1715, 1311, 1108 cm^–1; ¹H NMR (500.1 MHz, CDCl₃): δ = 3.57 (s, 2 H), 3.78 (s, 3 H), 3.89 (s, 3 H), 6.38 (s, 1 H), 7.23 (d, ³ J = 7.0 Hz, 2 H), 7.28–7.332 (m, 3 H). ¹³C NMR (125.7 MHz, CDCl₃): δ = 45.6 (CH₂), 53.3 (OCH₃), 54.7 (OCH₃), 127.7 (CH), 128.7 (2 CH), 129.3 (2 CH), 131.9 (CH), 136.1 (C), 147.7 (C), 165.5 (C=O), 167.0 (C=O). MS: m/z (%) = 234 (M⁺, 3), 219 (21), 188 (47), 116 (71), 91 (100). Anal. Calcd for C₁₃H₁₄O₄ (234.25): C, 66.66; H, 6.02. Found: C, 66.95; H, 6.41. Dimethyl 2-(4-Chlorobenzyl)fumarate (3b) Colorless oil; yield: 0.23 g (86%). IR (KBr): 3014, 2971, 1735, 1721, 1316, 1135 cm^–1. ¹H NMR (500.1 MHz, CDCl₃): δ = 3.46 (s, 2 H), 3.75 (s, 3 H), 3.85 (s, 3 H), 6.42 (s, 1 H), 7.32 (app d, ³ J = 7.1 Hz, 2 H), 7.45 (app d, ³ J = 7.1 Hz, 2 H). ¹³C NMR (125.7 MHz, CDCl₃): δ = 48.6 (CH₂), 53.3 (OCH₃), 54.3 (OCH₃), 128.6 (2 CH), 129.0 (2 CH), 133.8 (CH), 134.0 (C), 135.6 (C), 147.3 (C), 165.4 (C=O), 167.1 (C=O). MS: m/z (%) = 268 (M⁺, 1), 253 (10), 209 (29), 143 (57), 125 (100), 88 (38). Anal. Calcd for C₁₃H₁₃ClO₄ (268.69): C, 58.11; H, 4.88; Cl, 13.19. Found: C, 58.49; H, 5.19; Cl, 13.54. Dimethyl 2-[(1-Naphthyl)methyl]fumarate (3h) Pale-yellow oil; yield: 0.24 g (86%). IR (KBr): 3043, 2978, 1728, 1716, 1361, 1182 cm^–1. ¹H NMR (500.1 MHz, CDCl₃): δ = 3.76 (s, 3 H), 3.89 (s, 3 H), 4.11 (s, 2 H), 6.43 (s, 1 H), 7.06 (d, ³ J = 6.6 Hz, 1 H), 7.25–7.34 (m, 3 H), 7.78 (d, ³ J = 7.0 Hz, 1 H), 7.86 (d, ³ J = 7.1 Hz, 1 H) 7.95 (t, ³ J = 6.7 Hz, 1 H). ¹³C NMR (125.7 MHz, CDCl₃): δ = 39.2 (CH₂), 51.4 (OCH₃), 57.4 (OCH₃), 127.7 (CH), 127.8 (CH), 128.3 (CH), 128.7 (CH), 128.9 (C), 129.1 (C), 129.2 (CH), 129.4 (CH), 129.6 (CH), 130.4 (C), 131.1 (CH), 149.2 (C), 165.1 (C=O), 169.4 (C=O). MS: m/z (%) = 284 (M⁺, 2), 269 (12), 238 (41), 166 (46), 143 (69), 141 (100). Anal. Calcd for C₁₇H₁₆O₄ (284.31): C, 71.82; H, 5.67. Found: C, 72.34; H, 5.98. Dimethyl 1H-Indene-2,3-dicarboxylate (4) A mixture of fumarate 3c (1.0 mmol), Pd₂dba₃ (0.05 mmol), tris(2-furyl)phosphine (0.15 mmol), and Cs₂CO₃ (3.0 mmol) in 1,4-dioxane (3.0 mL) was stirred for 30 min at 25 °C. The reaction vessel was evacuated and back-flushed with N₂ (3×), and the mixture was stirred at 90 °C for 18 h. The mixture was then diluted with EtOAc (5.0 mL), sat. aq NH₄Cl (5.0 mL) was added, and the resulting mixture was stirred for an additional 30 min. The two layers were separated, and the aqueous layer was extracted with EtOAc (3 × 5 mL). The organic layers were combined, dried (MgSO₄), filtered, and concentrated in vacuo. The residue was purified by flash column chromatography [silica gel, hexane–EtOAc (5:1)] to give a yellow oil; yield: 0.21 g (89%). IR (KBr): 3028, 2957, 1735, 1728, 1371, 1107 cm^–1. ¹H NMR (500.1 MHz, CDCl₃): δ = 3.57 (s, 3 H), 3.71 (s, 3 H), 4.11 (s, 2 H), 7.11 (d, ³ J = 6.7 Hz, 1 H), 7.23–7.34 (m, 2 H), 7.57 (d, ³ J = 7.1 Hz, 1 H). ¹³C NMR (125.7 MHz, CDCl₃): δ = 46.2 (CH₂), 53.0 (OCH₃), 53.6 (OCH₃), 125.3 (CH), 125.9 (CH), 126.5 (CH), 129.1 (CH), 130.3 (C), 133.5 (C), 142.3 (C), 147.8 (C), 165.5 (C=O), 167.1 (C=O). MS: m/z (%) = 232 (M⁺, 4), 173 (16), 114 (37), 91 (100), 77 (61). Anal. Calcd for C₁₃H₁₂O₄ (232.24): C, 67.23; H, 5.21. Found: C, 67.89; H, 5.76.