Directing effect of Amide Function in Diastereoselective Reactions of Cyclopropenes and Cyclopropanes

Abstract

This thesis describes stereoselective directed reactions of cyclopropenes leading to the synthesis of a variety of densely substituted cyclopropanes as well as cyclopropyl containing bicyclic scaffolds. This thesis contains four chapters detailing the background, development, scope and limitations of the featured methodologies.First chapter presents a literature review on directed reactions of small cycles covering carbometalations and related reactions of cyclopropenes and cyclobutenes as well as directed C-H functionalizations of saturated three and four membered rings. Chapter two describes strain-release driven, carboxamide-directed addition of aryloxides across the double bond of cyclopropenes providing diastereomerically pure cyclopropyl aryl ethers. Facial selectivity of this transformation is controlled by strong coordination of the amide functionality to potassium cation, which serves as an efficient delivery vehicle for the aryloxide nucleophile. Chapter three describes a new cyclopropene-based linchpin for an expeditious synthesis of medium-sized heterocyclic compounds. The featured approach utilizes the directing ability of an amide functionality for Cu-catalyzed diastereoselective additions to cyclopropene double bonds, followed by an intramolecular stereoselective ring-closing metathesis facilitated by the rigid cyclopropane core. It was shown that ring sizes 7−10 can be routinely assembled using this approach, but the method fails for larger cycles (11- to 13- membered rings). Chapter four showcases previously unknown directed stereoselective hydrogenation of cyclopropenes in the presence of heterogeneous catalysts. The facial selectivity of the reaction is governed by the strong chelating effect of the carboxamide function to afford cis-hydrogenation. Additionally, directed site selective hydrogenolysis of cyclopropanes was demonstrated. It was shown that platinum-based catalyst facilitate cleavage of distant C2–C3 bond, while proximal C1–C2 bond is cleaved in the presence of palladium-based catalyst.