A 4-exo-dig Cyclocarbopalladation/8π Electrocyclization Cascade: Expeditious Access to the Tricyclic Core Structures of the Ophiobolins and Aleurodiscal

摘要

The design and elaboration of complex molecules from simple starting materials in the minimum number of synthetic steps is one of the most challenging goals in organic synthesis today. Towards this end, transition-metal-catalyzed processes have become a powerful tool for the construction of sensitive functionalized polycyclic molecules under very mild conditions. A particularly attractive goal in this field is the development of new methodologies for synthesizing cyclooctanoid ring systems.] This substructure is present in over 100 different natural products, many of which exhibit exceptional and broad-ranging biological activity. One of the most notable examples is the diterperne paclitaxel (taxol). However, because of the high degree of ring strain, transannular interactions, and unfavorable entropic and enthalpic factors, the synthesis of compounds with eight-membered rings remains difficult. Several authors have reported elegant approaches to such systems based on transition-metal catalysis. The most recent reports described the formation of bicyclic structures by using a rhodium catalyst in a one-pot operation. However, none of these approaches involved the direct formation of a 5,8,5-tricyclic skeleton.