Regioselective Synthesis of Substituted Imidate N-[1-Methyleneisobenzofuran-3(1H)-ylidene]benzenamines via Palladium-Catalyzed Tandem Heteroannulation of o-(1-Alkynyl)benzamides with Iodobenzene

Abstract

A variety of substituted imidate N-[1-methyleneisobenzofuran-3(1H)-ylidene]benzenamines have been prepared in good to excellent yields by the palladium-catalyzed tandem heteroannulation of o-(1-alkynyl)benzamides with iodobenzene. The products obtained from this process were unusual substituted N-[isobenzo­furan-3(1H)-ylidene]benzenamines. The tandem cyclization of readily available o-(1-alkynyl)benzamides and aryl iodides provided a powerful tool for the preparation of functionally substituted N-[isobenzofuran-3(1H)-ylidene]benzenamine compounds.

Keywords

isobenzofuran - o-(1-alkynyl)benzamide - iodobenzene - tandem - palladium catalysis

References and Notes

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General Procedure for the Preparation of N -[Isobenzo-furan-1 (3 H )-ylidene]benzenamine Compounds To a solution of o-(1-alkynyl)benzamides 1 (0.50 mmol) in MeCN (3.0 mL) was added 2,6-lutidine (1.00 mmol). The mixture was stirred for 10 min and Pd(PPh₃)₄ (5 mol%) and organic halides (0.60 mmol) were added. The resulting mixture was then heated under an argon atmosphere at refluxing temperature. When the reaction was considered complete, as determined by TLC analysis, the reaction mixture was cooled to r.t., quenched with a sat. aq solution of NH₄Cl, and extracted with EtOAc. The combined organic extracts were washed with H₂O and sat. brine. The organic layers were dried over Na₂SO₄ and filtered. The solvents were evaporated under reduced pressure. The residue was purified by chromatography on silica gel to afford the corresponding N-[1-(diphenylmethylene)isobenzofuran-3 (1H)-ylidene]benzenamine. Thus, starting with 1a (149 mg, 0.5 mmol) and iodobenzene 2a (122 mg, 0.6mmol), a yellowish solid product 4aa (273 mg, 73%) was isolated; mp 173-175 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 6.24 (d, J = 8.0 Hz, 1 H), 7.14-7.29 (m, 5 H), 7.35-7.41 (m, 5 H), 7.48-7.52 (m, 7 H), 8.00 (d, J = 7.6 Hz, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 120.77, 123.27, 123.42, 124.02, 124.76, 127.50, 127.86, 128.38, 128.59, 129.24, 129.26, 129.86, 130.66, 130.82, 131.68, 136.67, 137.80, 137.90, 145.64, 145.77, 153.98. IR (neat): 3052, 2923, 1681, 1013, 755, 693 cm^-¹. Anal. Calcd for C₂₇H₁₉NO: C, 86.84; H, 5.13; N, 3.75; O, 4.28. Found: C, 86.70; H, 5.06; N, 3.73; O, 4.35.

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The atomic coordinates for 4ac have been deposited at the Cambridge Crystallographic Data Centre (deposition number: CCDC 800275). The coordinates can be obtained on request from the Director Cambridge Crystallographic Data Centre. Postal Address: 12 Union Road, Cambridge CB2 1EZ, UK; Email: [e-mail]; fax: [phone]; tel.: [phone].