Conformational preferences of oxy-substituents in butenolide–tetrahydropyran spiroacetals and butenolide–piperidine spiro-N,O-acetals

Abstract

We describe the synthesis of a series of oxy-substituted butenolide spiroacetals and spiro-N,O-acetals by oxidative spirocyclisation of 2-[(4-hydroxy or 4-sulfonamido)butyl]furans. The axial–equatorial preference of each oxy-substituent is investigated (NMR) by an acid-catalysed thermodynamic relay of configuration between the spiro- and oxy-centres. The axial site is preferred for most oxy-substituents at synthetically useful levels. The potential origins of this preference are discussed in terms of a stabilising gauche effect combined with the influence of solvation. These results have relevance to the synthesis of bis(acetylenic)enol ether spiroacetals including AL-1 and related compounds.