Explorations in polyene chemistry

Abstract

Conjugated polyenes are an important class of organic molecules that have found applications in chemistry, medicine, and materials science. The ability of π-bond rich polyenes to rapidly generate structural complexity through domino pericyclic reactions renders them powerful reagents for synthesis. This thesis, which is submitted in publication format, describes the application of through-conjugated and cross-conjugated polyenes in step-economic natural product synthesis. The first synthesis of a family of all-(Z)-polyene hydrocarbons is also presented.

Chapter One details the first synthesis of natural products to feature (Z,Z,Z,Z)-tetraenes in domino 8π-6π electrocyclizations. The ten-step synthesis centred on the unprecedented four-fold cis-selective partial reduction of a conjugated tetrayne. Our studies suggest that the kingianins form in nature through redox-catalyzed formal Diels–Alder dimerizations rather than thermal concerted [4+2]-cycloadditions.

Chapter Two presents the first unified strategy for the synthesis of structurally distinct kingianin, endiandric acid, and kingianic acid natural products. Five natural products were prepared from a common tetrayne intermediate. The point of divergence involved the unconventional terminal alkylation of a conjugated tetrayne. Evidence for redox-catalysis in the biosynthesis of kingianic acid E was also obtained.

Chapter Three describes an unprecedented synthesis of unsubstituted all-(Z)-polyene hydrocarbons. The synthetic campaign allowed the structure and reactivity of all-(Z)-polyenes higher than octatetraene to be examined for the first time.

Finally, Chapter Four outlines the shortest synthesis of a pseudopterosin natural product reported to date. The tricyclic framework was forged using a triple Diels–Alder reaction sequence of an axially chiral cross-conjugated 1,1-divinylallene.