Cascade Pd(ii)-catalyzed Wacker lactonization–Heck reaction: rapid assembly of spiranoid lactones

Abstract

An unprecedented Pd-catalyzed cascade Wacker-Heck lactonization-cyclization sequence is reported. The process provides a facile approach to bi- and tricyclic spiranoid lactones in good yields. The reaction shows general substrate scope and a broad functional group tolerability. In addition, a rare 4-exo trig Heck-type cyclization is demonstrated.

Recent Developments in Pd0‐Catalyzed Alkene‐Carboheterofunctionalization Reactions

“…An unprecedented cascade Wacker-type lactonization/Heck reactiono fc ompound 124 was recently described that provided access to av ariety of angular tricyclich eterocycles( 125; Scheme 44). [54] This transformation was achieved by using as imple catalysts ystem that consisted of palladium(II) acetate and silver acetate with DMSO as the solvent. The desired products were obtained in generally good yield.…”

Palladium‐Catalyzed Double Cyclization Processes Leading to Polycyclic Heterocycles: Recent Advances

“…Synthesis of spiranoid lactones starting from carboxylic acids bearing two double bonds in suitable positions …”

“…A particularly interesting example of application of this concept was recently described by Tsvelikhovsky and co-workers. [32] It concern the formation of spiranoid lactones starting from carboxylic acids bearing two double bonds in suitable positions for the occurrence of a double cyclization. Specifically, the initial intramolecular nucleophilic attack of the carboxylic group to first double bond coordinated to Pd(II) was followed by intramolecular 5-exo-trig carbopalladation (by insertion of the second double bond) and -H elimination, with formation of the final product and Pd(0).…”

“…The latter was then reoxidized back to Pd(II) by the action of AgOAc, used as external oxidant (Scheme 29). [32] In a similar way, tricyclic spiroethers were synthesized starting from the corresponding dienols, as exemplified in Scheme 30. [33] Scheme 29.…”

“…Synthesis of spiranoid lactones starting from carboxylic acids bearing two double bonds in suitable positions. [32] Scheme 30. Synthesis of tricyclic spiroethers dienols with double bonds in suitable positions.…”