Investigation of the chemoselectivity and efficiency of the benzannulation reaction of electron poor aryl Fischer carbene complexes: Synthetic studies toward (+)-olivin.

摘要

Due to the unpredictability and inefficiency that have plagued the benzannulation reaction, it is felt that the true synthetic potential of this reaction has not yet been realized. Since most of the natural product applications of this reaction involve the formation of highly oxygenated aromatic ring systems, it was viewed as desirable to attempt to optimize the benzannulation reaction to produce these types of phenol products. Unfortunately, historically, highly oxygenated phenols have been derived from very electron rich aryl carbene complexes that have been shown to produce complex product mixtures, and are among the most inefficient and poorest yielding reactions of all benzannulation systems. It was therefore decided to conduct a systematic study of the benzannulation of electron poor Fischer carbene complexes with simple alkynes.; This work, while the continuation of a long standing theme in the study of Fischer chromium carbene complex reactivity, has shown that electron withdrawing groups in the para position of aryl carbene complexes increase the chemoselectivity for phenol formation. This work has also demonstrated that the presence of substituents in the ortho position of aryl carbene complexes are detrimental to phenol formation and the overall mass balance of the reaction regardless of the electronic nature of the ortho substituent. And finally, this work uncovered in a systematic way that larger alkyl groups on the oxygen heteroatom stabilizing substituent of the carbene carbon give rise to increased yields of the desired phenol product.; Another important aspect of this work is the progress that has been made toward the synthesis of (+)-olivin. At the outset of this work, the synthesis was at a very undeveloped stage. The lengthy, workman-like synthesis of the crucial alkyne, while capable of producing material for the convergent step, was not up to par with the previous synthetic efforts of other groups. This work has effectively eradicated any doubt about the first half of the synthesis leading up to the convergent step, and has given a boost to the overall state of the synthesis by significantly shortening what will be the longest linear sequence.