Assembly of 3-Substituted Isocoumarins via a CuI-Catalyzed Domino Coupling/Addition/Deacylation Process

Abstract

An efficient strategy for the synthesis of a variety of 3-substituted isocoumarins has been developed. The reaction proceeded from o-halobenzoic acids and 1,3-diketones via a copper(I)-catalyzed domino reaction in DMF under the action of K(3)PO(4) at 90-120 °C without a ligand to afford the corresponding 3-substituted isocoumarin derivatives in good to excellent yields. o-Halobenzoic acids could be o-iodobenzoic acid, o-bromobenzoic acid, and o-chlorobenzoic acid derivatives. 1,3-Diketones could be alkyl- and aryl-substituted 1,3-diketones.

Simple Method for sp2–sp3 and sp3–sp3 Carbon–Carbon Bond Activation in 2-Substituted 1,3-Diketones

“…Colorless oil; yield: 0.186 g (77% 13 C NMR (100 MHz, CDCl 3 ): δ = 26. 6, 33.2, 34.9, 53.4, 126.3, 128.4, 128.5, 139.8, 201.5 5, 46.6, 127.1, 128.5, 128.6, 128.8, 128.8, 129.4, 130.2, 133.7, 192.8 22.6, 27.5, 29.1, 29.2, 29.3, 31.8, 33.5, 47.3, 128.8, 128.8, 133.6, 134.5, 193 …”

“…21-7.32 (m, 6 H). 13 C NMR (100 MHz, CDCl 3 ): δ = 50. 73,117.3,125.7,126.9,127.7,128.7,129.2,130.2,132.2,141.6,152.0.…”

“…12-7.14 (m, 4 H), 7.27-7.37 (m, 7 H), 7.77 (d, J = 2.8 Hz, 1 H), 8.07 (dd, J = 8.9, 2.8 Hz, 1 H). 13 C NMR (100 MHz, CDCl 3 ): δ = 50. 6, 116.1, 124.4, 126.5, 127.3, 128.9, 129.2, 131.5, 141.0, 141.7, 159 ,4.95;N,4.59.…”

“…1 H NMR (400 MHz, CDCl 3 ): δ = 1.55 (d, J = 7.1 Hz, 3 H), 3.78 (s, 3 H), 3.99 (q, J = 7.1 Hz, 1 H), 5.01 (s, 1 H), 5.07 (s, 1 H), 6.66 (dd, J = 7.9, 2.0 Hz, 1 H), 6.69 (d, J = 2.0 Hz, 1 H), 6.77 (d, J = 7.9 Hz, 1 H), 6.80-6.84 (m, 2 H), 7.10-7.13 (m, 2 H). 13 C NMR (100 MHz, CDCl 3 ): δ = 22.1, 43.2, 55.2, 113.7, 114.7, 115.1, 119.9, 128.4, 138.7, 140.2, 141.4, 143.2, 157.7 …”

“…10 Additionally, a copper-catalyzed arylation of 1,3-diketones with aryl halides to give α-aryl ketones was reported by Lei and co-workers in 2010. 11 Later, a method for the synthesis of isocoumarins through copper iodide-catalyzed tandem acylation and cyclization was developed by Fan,12 Xi, 13 and Yao, 14 and their respective co-workers. Wang and co-workers recently reported syntheses of amides, α-keto amides, and 1H-pyrrol-3(2H)-ones from amines and 1,3-diketones, in which the cleavage of C-C bonds was mediated by peroxides.…”