sp3-sp2 Suzuki-Miyaura Cross-Coupling of Primary Organoborons Containing Saturated Heterocycles and Aryl Halide Electrophiles

This thesis describes the development of methodology for the Pd-catalysed sp2-sp3 Suzuki-Miyaura cross-coupling (SMCC) of saturated heterocyclic primary organoborons. The aim of the work undertaken is to provide a robust arylation procedure that could be readily applied to synthetic routes in medicinal chemistry programmes.

Chapter 1 introduces a selection of biologically active compounds that contain the alkyl-aryl motif associated with this type of SMCC reaction. It then explores the range of primary organoboron reagents that have been applied previously in primary sp2-sp3 SMCC reactions and discusses the current limitations of these methods. Previous work in the O’Brien group on primary sp2-sp3 SMCC of saturated heterocycles is also detailed. Chapter 2 is concerned with the synthesis of five different saturated heterocyclic primary organoboron reagents from commercially available reagents.

Chapter 3 provides an evaluation of three 3-substituted organoboron derivatives and subsequent evaluation of their performance in SMCC reactions. The chapter also details a development of the scope of aryl halides that can be effectively cross-coupled with each of the organoboron compounds. Alongside this, a brief evaluation of a mechanistic aspect of the SMCC reaction is discussed using an enantiomerically pure 2-substituted pyrrolidine organoboron reagent.