Diastereospecific approach to (±)-samin and 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane (furofuran) lignans using the Ireland–Claisen rearrangement of unsaturated oxamacrolides

Enolate Claisen rearrangement of the unsaturated oxamacrolide 28 leads specifically, after reduction, to the tetrahydro-3-furylmethanol 30, via a boat-like transition state 29. Initial attempts to obtain a macrolide related to 28 by O-alkylation of the model β-hydroxy ester 12 using acetimidate 13 were inefficient. Key steps in the successful preparation of the macrolide 28 are Michael addition of a mono-protected (Z)-but-2-ene-1,4-diol 23 to an α-sulfonyl cinnamate 26 and lactonization of the derived hydroxy acid 27c using Mukaiyama's reagent. Subsequent oxidative cleavage of the vinyl group in the tetrahydrofuran 30 gives (±)-samin 9, a precursor of both symmetrical and unsymmetrical furofuran lignans 8.