2-acetonyl-2,4-di(hydroxy)tetrahydropyrans versus ?-pyrones: A chemodivergent issue for the condensation of acetylacetone dianion equivalents with a,ß-disubstituted ß-hydroxyaldehydes leading to potential new synthons for spiroketals

Abstract : In order to develop a new route to ketal or spiroketal subunits present in numerous natural products, condensation of acetylacetone bis(silyl)enol ether 2-Si or acetylacetone lithium dianion 2-Li with various anti a,ß-disubstituted ß-hydroxy aldehydes 11 was studied. It has been shown that under Lewis acid-promoted Mukaiyama conditions it is possible to realize such condensation reactions without formation of the well-known Danishefsky ?-pyrones 8. The required 2-acetonyl-2,4-dihydroxytetrahydropyrans 1 for further synthetic purposes were prepared in good to high yields from the intermediate acyclic aldol adduct 7. Particularly crucial are i) the deprotection conditions of the O-silyl protected acyclic intermediate 7 with tetrabutylammonium fluoride in dimethylformamide, and ii) the subsequent montmorillonite K10-promoted protection of the hemiketal 1 hydroxy group. The parameters governing the stereoselectivity of the initial condensation reaction have been studied. Under apparent Felkin or anti-Felkin/Cram-chelate conditions, syn, anti-adducts are obtained with high selectivity from acetylacetone bis(silyl) enol ether 2-Si. Partial modulation of the stereoselectivity can be achieved through condensation of the acetylacetone lithium dianion 2-Li with aldehydes bearing bulky O-silyl protecting groups which allows a preferential access to the anti, anti triads.