Multi-bond forming processes : making and using dendralenes

Abstract

The theme of the research presented herein is the recognition and understanding of multi-bond forming processes and their utility in organic synthesis, and the development and application of such reactions to synthesise dendralenes and demonstrate their significant potential in complex molecule synthesis. Multi-bond forming processes are reactions or sequences thereof that construct two or more covalent bonds in a single synthetic operation. They are being increasingly embraced in modern synthesis. Chapter One is a review that classifies, contrasts and analyses different kinds of multi-bond forming process, highlighting their evolution and application in today's most sophisticated syntheses, and presenting an outlook for what the future may hold as the science of synthesis continues to develop. Chapter Two reports the application of multi-bond forming processes in the synthesis of conjugated frameworks, including butadienes, dendralenes, allenyl alcohols, benzofulvenes, and indenes. The development of a robust and highly functional group-tolerant palladium(0)-catalysed cross-coupling reaction allows access to these functional molecules with exceptional step economy. Furthermore, this new technology uses readily available and stable propargylic diols as substrates, obviating the classical need for conversion into reactive halogens or pseudohalogens. Chapter Three showcases the utility of conjugated hydrocarbons in rapid and efficient complex molecule synthesis. Dendralenes are subjected to enantioselective organocatalytic Diels-Alder reactions. The products of domino double-Diels-Alder reactions are found to have significantly enhanced enantiopurity compared to products of a single Diels-Alder reaction, by virtue of the Horeau effect. Until this point, the potential of dendralenes in catalytic enantioselective synthesis had remained untapped. The newly developed organocascade generates no less than four carbon-carbon bonds, and lays the platform for the very efficient synthesis of enantiopure, complex polycyclic frameworks from simple achiral, acyclic hydrocarbons.