Total Syntheses of the Coumarin-Containing Natural Products Pimpinellin and Fraxetin Using Au(I)-Catalyzed Intramolecular Hydroarylation (IMHA) Chemistry

Abstract

The title natural products (1 and 2, respectively) have been synthesized by Au(I)-catalyzed intramolecular hydroarylation (IMHA) of the relevant aryl propiolate esters (e.g., 13), which were themselves formed by reaction of the corresponding phenols with either 3-(trimethylsilyl)propiolic acid or propiolic acid and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride or dicyclohexylcarbodiimide. (±)-Purpurasol (3) was readily derived from fraxetin (2) by established procedures.

Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular Complexity

“…The cyclization of aryl propiolates gives coumarin derivatives, including the natural products pimpinellin ( 464 ), fraxetin, and purpurasol (Scheme 152 ). 407 …”

Gold‐Catalyzed Hydrofunctionalizations and Spiroketalizations of Alkynes as Key Steps in Total Synthesis

“…The generally observed high selectivity for the 6‐ endo over the 5‐exo pathway in these transformations is also observed in the case of internal alkynes as in the total synthesis of (−)‐Cryptopleurine . The coumarin natural products Pimpinellin, Fraxetin and (±)‐Purpurasol could nicely be accessed by a similar 6‐ endo ‐ dig hydroarylation reaction as well as the tetracyclic core of Berkelic acid …”

Metal-Catalyzed Routes for the Synthesis of Furocoumarins and Coumestans

“…Very recently, Banwell and coworkers have reported the total synthesis of pimpinellin 59, a naturally occurring angelicin derivative with remarkable inhibiting properties of the trichothecene toxin biosynthetic pathway [113] and some nitric oxide synthase enzymes [114], starting from readily available vanillin 57 (Scheme 25) [115]. In the last step of the process, the pyrone ring of 59 was generated by intramolecular hydroarylation of the 4-benzofuranyl alkynoate 58, a reaction that was effectively catalyzed by the cationic gold(I)-phosphine complex 60 under mild conditions.…”