2-Acetonyl-2,4-di(hydroxy)tetrahydropyrans versus γ-Pyrones: A Chemodivergent Issue for the Condensation of Acetylacetone Dianion Equivalents with α,β-Disubstituted β-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 α,β-disubstituted β-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 γ-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.

Key words

silyl enols ethers - dianions - aldol reactions - cyclizations - chemoselectivity - diastereoselectivity - spiro compounds

References

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1

Current address: Vivien Henryon, Rhône-Poulenc industrialisation, 24 Avenue Jean Jaurès, 69153 Décines-Charpieu, France. E-mail: [e-mail].

2

Current address: Jean-Pierre Férézou, Far-Manguinhos, Instituto Oswaldo Cruz, Rua Sizenando Nabuco, 100 Manguinhos, CEP 21041-250 Rio de Janeiro/RJ, Brazil, E-Mail: [e-mail].

13

See Ref. [7] .

26

See Ref. [20] This condensation reaction, performed in the presence of TiCl₂(OPr-i)₂ led to an excellent Felkin syn-selectivity (>95:5).