Abstract:
The acyl-Claisen rearrangement is a powerful [3,3]-sigmatropic rearrangement of an allylic amine and an acyl chloride derived ketene. The α,β-substituted-γ,δ-olefinic amide 32 derived from this rearrangement has been demonstrated to be a powerful scaffold for elaboration via a number of routes. This thesis describes the extension of acyl-Claisen rearrangement methodology to produce di-aromatic amides where previously only mono-aromatic amides had been produced. A screen of Lewis acids was carried out in an attempt to optimise rearrangement conditions and a variety of aromatic substrates of varying substitution were utilised. Elaboration of diaromatic amides was then carried out to produce novel tetraphenyl-tetrahydrofuran 109c and progress was made towards the synthesis of resveratrol dimer tricuspidatol A 109b. Finally the synthesis of magnosalicin 112 was completed via mono-aromatic amide 32m. The acyl-Claisen rearrangement methodology was further extended in an attempt to produce an asymmetric variant. Preparation of 3-substituted morpholines 181a-g from amino alcohols was carried out and subsequent allylation of these morpholines provided chiral substrates for the acyl-Claisen rearrangement. Rearrangement of many of these chiral allylic morpholines 182a-h/183a-h proved successful and analysis of the pseudoenantiomeric amides produced was carried out by chiral HPLC. Diastereoselectivity ranged from 50:50 to 92:8, although yields also varied widely (14 – 98%). Choosing the most robust rearrangement from this series we carried out a screen of acyl chlorides, establishing a wide range of suitable substituents.
