Exploration of Ligand Effects, Substrate Effects and Reactor Effects on Macrocyclization via Ring-Closing Metathesis: A Rational Approach to Efficient Cyclization

THESIS
Exploration of Ligand Effects, Substrate Effects and Reactor Effects on Macrocyclization via Ring-Closing Metathesis: A Rational Approach to Efficient Cyclization 
Monfette, Sebastien, Ph.D., UNIVERSITY OF OTTAWA , 2011
Abstract:
Olefin metathesis is credited with having transformed the way chemists think about the manipulation of C=C bonds, the success-story of which culminated in the highest of accolades to Schrock, Grubbs and Chauvin in 2005. It is, however, difficult to reconcile the groundbreaking effect that olefin metathesis had on organic synthesis, with its limited industrial applications.
Nearly twenty years following the publication of the first well-defined Ru metathesis catalyst, the RCM reaction remains largely confined to the research setting. The low turnover numbers achieved by the Grubbs catalyst is the chief limiting factor preventing industrial uptake. Clearly, more efficient catalysts and reaction methodologies are needed to render RCM industrially viable. This thesis describes various approaches towards this goal.
As macrocyclic targets are highly prized in the industry, a mechanistic investigation of their formation by the Grubbs and pseudohalide catalysts was performed. This study revealed that different reaction pathways are operative for different catalysts. While the first-generation catalyst effects RCM macrocyclization by the traditional, direct path, the second-generation catalysts afford macrocyclic products through a concentration dependent oligomerization-backbiting pathway.
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