Synthesis of the Tetracyclic Core of Berkelic Acid Using Gold(I)-Catalyzed Hydroarylation and Oxidative Radical Cyclizations

Abstract

A synthetic approach to the tetracyclic core of berkelic acid is reported using gold(I)-catalyzed intramolecular hydroarylation and oxidative radical cyclizations to effect the key ring-forming steps. The carboxylic acid was introduced via a late-stage palladium-catalyzed carbonylation to afford the core tetracycle with the correct relative stereochemistry for the natural product.

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

“…An application of the formation of 2 H -chromenes by intramolecular hydroarylation is found in the synthesis of the tetracyclic core of berkelic acid ( 462 ) (Scheme 151 ). 406 …”

Total Synthesis and Structural Confirmation of the Antimalarial Naphthopyrone Lasionectrin

“…Because of the instability of iodide 17 , it was immediately protected as the acetate 18 . Attempts to effect carbonylation of the iodide to give ester 19 were unsuccessful using a variety of methods, with protodehalogenation predominantly occurring. Eventually, carbonylation was successfully achieved in a sealed tube at 120 °C under a carbon monoxide atmosphere in the presence of palladium acetate and triethylamine …”

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 …”

“…[15] The coumarin natural products Pimpinellin, Fraxetin and (AE)-Purpurasol could nicely be accessed by a similar 6-endo-dig hydroarylation reaction [16] as well as the tetracyclic core of Berkelic acid. [17] The akuammiline alkaloid (À)-Aspidophylline A was isolated from Malayan Kosia Singapurensis in 2007 and shows promising activity against human KB nasopharyngeal cancer cells. [18] to form tetracycle A, described by Wang and co-workers.…”