Intramolecular Palladium-Catalyzed Oxidative Coupling on Thiophene and Furan Rings: Determinant Role of the Electronic Availability of the Heterocycle

Abstract

The cyclization of N-allyl-N-carbetoxy-substituted aminothiophenes and furans was performed by intramolecular Pd(II)-catalyzed oxidative coupling. The process involves a nucleophilic attack of a heteroaromatic carbon to the internal carbon of the π-olefin complex through a 5-exo-trig ring-formation. Better conditions required PdCl₂(MeCN)₂ as catalyst, CuCl₂ as co-catalyst and an environmentally friendly reoxidant such as O₂ to promote the catalytic cycle.

coupling - cyclizations - furans - fused ring systems - palladium

References and Notes

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Experimental Procedure
A mixture of PdCl₂(MeCN)₂ (39 mg, 0.15 mmol) and CuCl₂ (20 mg, 0.15 mmol) in DMF (13 mL) was stirred at r.t. for 30 min under oxygen atmosphere. After addition of a solution of 5a (225 mg, 1 mmol) in DMF (13 mL), the mixture was heated at 100 °C for 2 h under an O₂ atmosphere. The mixture was washed with brine and extracted with Et₂O (2 × 20 mL). The organic layer was dried over Na₂SO₄ and the solvent removed under reduced pressure. The residue was chromatographed on a silica gel column with light PE-EtOAc (10:1) as eluent to give 6a.
Data for 6-Carbethoxy-2,4-dimethyl-6 H -thieno[2,3- b ]pyrrole (6a) Oil. IR (nujol): 1635 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.45 (3 H, t, J = 7.2 Hz), 2.20 (3 H, s), 2.53 (3 H, s), 4.45 (2 H, q, J = 7.2 Hz), 6.65 (1 H, s), 7.11 (1 H, s). ¹³C NMR (100 MHz, CDCl₃): δ = 11.4 (q), 14.7 (q), 16.3 (q), 63.8 (t), 114.7 (d), 117.7 (s), 120.3 (d), 133 (s), 136.6 (s), 150.1 (s), 162.9 (s). MS: m/z 223 [M⁺]. Anal. Calcd for C₁₁H₁₃NO₂S: C, 59.17; H, 5.87; N, 6.27. Found C, 59.01; H, 6.06; N, 6.41.

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<A NAME="RD40707ST-13">13</A>

6-Carbethoxy-4-methyl-2-phenyl-6 H -furo[2,3- b ]pyrrole (8e)
Oil. IR (nujol): 1635 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.50 (3 H, t, J = 7.1 Hz), 2.19 (3 H, s), 4.50 (2 H, q, J = 7.1 Hz), 6.77 (1 H, s), 6.79 (1 H, br s), 7.24-7.26 (1 H, m), 7.40 (2 H, dd, J = 7.8, 7.5 Hz), 7.70 (2 H, d, J = 7.5 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 12.0 (q), 14.8 (q), 63.8 (t), 100.2 (d), 115.0 (s), 115.4 (s), 116.0 (d), 123.6 (d), 127.3 (d), 129.1 (d), 131.7 (s), 147.4 (s), 149.4 (s), 154.5 (s). MS: m/z = 269 [M⁺]. Anal. Calcd for C₁₆H₁₅NO₃: C, 71.36; H, 5.61; N, 5.20. Found C, 71.32; H, 5.80; N, 5.05.

<A NAME="RD40707ST-14">14</A> Beccalli EM. Broggini G. Martinelli M. Sottocornola S. Synthesis  2008,  136