A stereospecific synthesis of advanced precursors of the dictyol diterpenes using the alicyclic Claisen rearrangement

Abstract

Claisen rearrangements of the O-silyl enolates derived from macrolides (15a) and (15b) proceed stereospecifically to give the perhydroazulenes (23a) and (24), which contain appropriate functionality for further elaboration to members of the dictyol group of diterpenes [e.g., dictyol C (1)]. The rearrangements proceed via a boat conformation (Scheme 1), as expected from previous model studies, in which the cyclopentyl residue is readily accommodated in a favourable trans-diequatorial position. The key trans-2,3-disubstituted cyclopentanone (11a) was prepared by a conjugate addition–trapping sequence from the dithiane (10), cyclopent-2-enone, and ethyl iodoacetate. Subsequent manipulation of the protecting groups then gave the hydroxy esters (12a) and (14a), which were directly lactonised to give the macrolides (15a) and (15b)via the corresponding lithium alkoxides.