Investigation into Higher Dendralenes

Abstract

As synthetic organic chemists, one of our most important desires is to synthesize complex target molecules efficiently in the shortest time and lowest step count, with cheap starting materials. One of the classes of fundamental hydrocarbons, dendralenes, acyclic cross-conjugated alkenes, have great potential to build up complex polycyclic carbon frameworks rapidly due to having the ability to participate in diene-transmissive Diels–Alder sequences. These π-bond rich hydrocarbons are therefore attracting a growing interest. The goals of the research presented in this thesis are not only to investigate possible synthetic applications of dendralenes but also to understand in a broad sense how fundamental aspects of structure impacts upon chemical stability and reactivity. A detailed literature survey can achieve two goals: it forms the basis of a future research program and can also improve current knowledge. Chapter One of this thesis is a review of the synthesis of dendralenes, organized on the basis of which key carbon-carbon bond is formed during their synthesis. Categorization of previously reported syntheses, including interpretations of these publications in terms of synthetic strategies and tactics are presented accordingly. The work detailed in Chapter Two describes the first syntheses of the parent (unsubstituted) higher dendralenes, specifically [9]dendralene to [12]dendralene, and an investigation into the spectroscopic properties and chemical reactivity of the first ten members of this family ([3]dendralene to [12]dendralene). These studies reveal the first documented case of diminishing alternation in behavior in a series of related chemical structures. This dampening oscillatory effect in both spectroscopic measurements and chemical reactivity is traced to conformational preferences, through a comprehensive series of computational studies performed by a collaborator. Previous studies showed that the Diels–Alder reaction between parent [4]dendralene and an excess quantity of the electron deficient dienophile N-methylmaleimide (NMM) at room temperature produces five different products. Two of these products contain a hydrophenanthrene carbon skeleton, which is the backbone of many different medicinal drugs. It was postulated that substituents on the [4]dendralene framework might XI XII influence the outcome of this very powerful reaction, thereby promoting its application in efficient synthesis. The work presented in Chapter Three describes the first synthesis of the five possible mono-substituted [4]dendralenes, which required the development of new methods in conjugated alkene synthesis. The reactivity of these hydrocarbons towards the dienophile N-methylmaleimide was performed, in order to document the influence of the role of substituent on the selectivity of the Diels–Alder sequence. Conclusions are made, on the basis of these findings, regarding the application of dendralenes in the synthesis of biologically active natural products and their analogues. The research described in Chapter Four is also directed towards making dendralenes more useful in target synthesis. In this chapter we report the synthesis of 2-halo[4]dendralenes, and efforts to control chemoselectivity, site selectivity and enantioselectivity in their Diels–Alder reactions towards certain dienophiles.