The total synthesis of (±)-indolizidines 235B and 235B′

Abstract

The total synthesis of racemic indolizidines 235B 1 and 235B′2 is described, in which the key step is the intramolecular thermal cycloaddition of the (Z)-N-alkenylnitrones 10b and 10a, respectively. Cyclisation of the isoxazolidines 12, followed by reductive N–O bond cleavage, epimerisation of the resulting axial hydroxymethyl side chain to the equatorial configuration, and further reduction to a methyl group gave the target molecules. Intramolecular cyclisation of the related nitrone 18, a potential precursor to the solenopsins, was less regioselective, affording a 6:1 mixture of the adducts 19 and 20, which indicates a dependence on the nature of the substituent α to nitrogen.