The Preparation and Evaluation of Electron Poor Benzylidene Fischer Carbene Complexes: Studies Toward the Total Synthesis of (+)-Olivin

The continued exploration into the fate of the benzannulation reaction is put forth using the electronic nature of substituents on the aryl ring of benzylidene Fischer carbene complexes as a handle to predict, using σ-para values as a guide, the outcome of the reaction based on the accepted mechanism. The design of this work focuses on evaluation of the synthetic utility of the benzannulation reaction and the means by which this reaction may be improved to be a better synthetic tool in the preparation of complex natural products as this is illustrated in our ongoing total synthesis of (+)-olivin which uses the benzannulation reaction as the key convergent synthetic step. To accomplish these tasks, the preparation of several electron poor benzylidene Fischer carbene complexes was carried out and their reaction with simple alkyne substrates studied. While much is known about the preparation of electron rich benzylidene Fischer carbene complexes, little is known about the preparation of their electron poor counterparts. Thus efforts toward developing useful preparative methods of these elusive targets has also been studied. While the use of both carbon and oxygen based aryl substituents has been explored, to date the preparation of benzylidene carbene complexes containing oxygen based aryl substituents has been exploited to a greater degree since these systems carry more immediate synthetic importance. This is so because the skeletal core of many of the natural products that have been targeted with the benzannulation reaction including (+)-olivin contain a highly oxygenated polycyclic aromatic core. The enhancement in efficiency of the benzannulation reaction using this synthetic methodology is demonstrated by the successful completion of the convergent synthetic step in the total synthesis of (+)-olivin.