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.

Synthesis of Pandamarilactone-1

“…In this context, we reported two general methods for butenolide spiro-N,O-acetal formation from ω-aminoalkylfurans. 8 In the first, oxidation with MCPBA generates the hydroxybutenolide; in the second, 1 O 2 generates the analogous methoxybutenolide. In both methods, subsequent addition of H 2 SO 4 was required in order to complete spiro-N,O-acetalization and only sulfonyl protecting groups were compatible with this overall process.…”

“…Following strategically similar lines, we projected a synthesis of pan­damari­lactone-1 from symmetrical di­(furyl­alkyl)­amine 3 (Scheme ), the oxidation of which would allow spirocyclization and elimination to complete the route. In this context, we reported two general methods for butenolide spiro- N , O -acetal formation from ω-amino­alkyl­furans . In the first, oxidation with MCPBA generates the hy­droxy­butenolide; in the second, 1 O 2 generates the analogous methoxy­butenolide.…”