Short and convenient synthesis of two natural phthalides by a copper(I) catalysed Sonogashira/oxacyclisation copper(I) process

Recent advances and perspectives in copper-catalyzed Sonogashira coupling reactions

“…Sonogashira coupling has also been used for the total synthesis of naturally occurring phthalides (AE)-herbaric acid and (AE)-(4-methoxybenzyl)-5,7-dimethoxyphthalide from terminal alkynes and 2-iodobenzoic acid derivatives via 5-exodig cyclisation with high stereo-, regio-and chemoselectivities (Scheme 35). 55…”

Preparation of 3‐Alkylidenephthalides: Recent Advances

“…A mechanistic rationale was proposed to explain the regioselec- In 2014, Petrignet et al reported the total regioselective synthesis of two natural phthalide products isolated from Australian liverwort Frullania falciloba, [33] (�)-herbaric acid and (�)-(4-methoxybenzyl)-5,7-dimethoxyphthalide starting from 2iodo-4,6-dimethoxybenzoic acid (Scheme 27). [34] The key step of the sequence included a copper-catalyzed tandem crosscoupling and oxacylization reaction of terminal alkynes and 2iodo-4,6-dimethoxybenzoic acid via 5-exo-dig cyclisation with high stereo-, regio-and chemoselectivity. The reaction proceeded in the presence of the CuI catalyst (20 mol%) and K 2 CO 3 (2.0 equiv) in DMF at 80 °C with 4-methoxyphenylacetylene or 3,3-diethoxyprop-1-yne to yields phthalides in a very regioselective manner.…”

Copper-catalyzed deacetonative Sonogashira coupling

“…16 This approach proved useful and sometimes even indispensable in performing macrocyclizations, 17 the domino construction of a plethora of various heterocycles, 18 assembly of stable organic radicals 19 and supramolecular architectures, 20 and the preparation of natural products and their derivatives ( e.g. carbohydrates, 21 steroids, 22 core structure of terpenoid brownin F, 23 antibiotic anisomycin, 24 rosuvastatin analogs, 25 alkaloids isocryptolepine 26 and lennoxamine, 27 bioactive benzofurans, 28 butenolides, 29 and phthalides 30 ).…”