2-Acetonyl-2,4-di(hydroxy)tetrahydropyrans versus gamma-pyrones: A chemodivergent issue for the condensation of acetylacetone dianion equivalents with alpha,beta-disubstituted beta-hydroxyaldehydes leading to potential new synthons for spiroketals

In order to develop a new route to ketal or spiroketal subunits present in numerous natural products, condensation of acetylacetonebis(silyl)enol ethe r 2-Si or acetylacetone lithium dianion 2-Li with various anti alpha,beta - disubstituted beta -hydroxy aldehydes 11 was studied. It has been shown tha t under Lewis acid-promoted Mukaiyama conditions it is possible to realize such condensation reactions without formation of the well-known Danishefsky gamma -pyrones 8. The required 2-acetonyl-2,4-dihydroxytetrahydropyrans 1 for further synthetic purposes were prepared in good to high yields from th e intermediate acyclic aldol adduct 7. Particularly crucial are i) the depr otection conditions of the O-silyl protected acyclic intermediate 7 with te trabutylammonium. fluoride in dimethylformamide, and ii) the subsequent mon tmorillonite K10-promoted protection of the hemiketal 1 hydroxy group. The parameters governing the stereo selectivity of the initial condensation rea ction have been studied. Under apparent Felkin or anti-Felkin/Cram-chelate conditions, syn, anti-adducts are obtained with high selectivity from acety lacetone bis(silyl) enol ether 2-Si. Partial modulation of the stereoselect ivity can be achieved through condensation of the acetylacetone lithium dia nion 2-Li with aldehydes bearing bulky O-silyl protecting groups which allo ws a preferential access to the anti, anti triads.