Studies toward Augmented Carbene/Alkyne Cascade Reactions and Ruthenium Catalysts for Propargylic Substition

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2015-12

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Abstract

This thesis presents three main projects. The first project presents synthetic strategies toward augmented cascade reactions. The second part discusses the synthesis of a ruthenium catalyst and its application for propargylic substitution. The third part describes an improvement of a Robinson annulation for the synthesis of aplykurodinone 1. Alkyne/cascade reactions are highly effective processes in organic chemistry, and they can provide complex molecules in a single synthetic method. Our approach is based on a rhodium-catalyzed diazo-decomposition of readily available starting materials. Then the reaction goes through metal-carbene and alkyne insertion, and finally C-H insertion or alkyl migration. Because of ring-strain and steric effects, a cyclic syn-alkynyl diazoacetate approach underwent direct C-H insertion. A linear di-alkynyl diazoacetate approach underwent a gold-catalyzed cascade reaction to generate a polycyclic product. Substituted alkynes are widely used for organic polymers and pharmaceuticals. Furthermore, propargylic substitution is an important transformation of substituted alkynes. Based on reported metal-catalyzed propargylic substitutions, we designed and synthesized various ruthenium tris(pyrazoly)borate complexes to test propargylation. When studying ruthenium-catalyzed reactions, we discovered that the inorganic salt (NaPF6) has catalytic activities toward propargylic substitution. Aplykurodinone 1 was isolated from the skin of sea slugs belonging to the Aplysiidea family and might be part of the animals defense mechanism. We developed a synthetic route toward aplykurodinone 1. A challenging transformation in our synthetic route used a Robinson annulation to form the bicyclic core struture of aplykurodinone 1. We modified the Robinson annulation to perform this reaction consistently and efficiently.

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Keywords

Cascade reactions, Propargylic substitution

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