[3,3]-rearrangements of phosphonium ylides and dipole-induced dipole interactions for molecular recognition in DNA.

Abstract

Phosphonate esters have far-reaching applications as synthetic building blocks for bioactive natural products and as precursors to alpha-aminophosphonic acids. While they are important synthetic intermediates, methods for the preparation of phosphonate esters bearing multiple substituents at the alpha position are relatively limited. The [3,3]-sigmatropic rearrangement of phosphonium ylides, a new reaction manifold, was developed and explored as a method for synthesizing phosphonate esters with diverse and complex structure. The phosphonium ylides were prepared by reacting an allylic alcohol with an activated phosphorus (III) species followed by addition of a diazo compound and an transition metal catalyst. Heating the ylides induces a [3,3]-sigmatropic rearrangement to form a new carbon-carbon bond. Chapter II introduces the reaction and discusses the mechanism which was elucidated through various methods including <super> 31</super>P NMR experiments, crossover experiments, and a modeling study. The scope of the phosphonium ylide rearrangement was investigated by surveying a range of allylic alcohols with various substitution patterns and functional groups as well as numerous diazo compounds. Chapter III discusses the diversity of viable reagents for the rearrangement and the numerous phosphonate esters that can be generated using this new method. In addition, subsequent transformations of the rearrangement products were explored such as Homer-Wadsworth-Emmons olefinations to yield a variety of nonsymmetrical, skipped dienes and electrophilic amination reactions to yield alpha-aminophosphonic acid derivatives. The development of novel base pairs for DNA has provided methods for expanding the genetic code as well as for studying the details of protein-nucleic acid interactions. A molecular recognition element commonly used in crystal engineering, the dipole-induced dipole interaction, was incorporated into a novel base pair for DNA. Chapter I presents the molecular recognition motif, the nitro&middot;&middot;halogen interaction, and how it has proven useful in directing supramolecular assemblies. Chapter IV discusses how the nitro&middot;&middot;halogen contact was incorporated onto non-natural nucleobases and into oligonucleotides. Thermal denaturation experiments were performed to evaluate the stability and specificity of the interaction in the context of DNA.