The development of a novel double allylboration reaction: Synthesis of 1,5-diols and progress towards the synthesis of amphidinol 3.

Abstract

As an extension of our program in acyclic stereochemistry and allylboration methodology, a novel double allylboration reaction was developed. The reaction combines a double allylboration reagent and two different aldehydes to produce either (<italic>E</italic>)-1,5-<italic>anti</italic>- or (<italic>Z</italic>)-1,5-<italic> syn</italic>-diols with an internal olefin. The relative stereochemistry of the diols and the geometry of the olefin formed during the reaction are dependent on the substitution pattern of the double allylboration reagent. The methodology is compatible with simple or highly functionalized aldehydes and is capable of quickly building molecular complexity from simple starting materials. The (<italic>Z</italic>)-1,5-<italic>syn</italic>-diol products were used to develop a synthesis of <italic>trans</italic>-2,6-disubstituted 5,6-dihydro-2<italic> H</italic>-pyrans. The pyrans were formed by selective silyl protection of the allylic alcohol of the 1,5-diol and mesylation of the homoallylic alcohol moiety. Deprotection of the silyl-protected alcohol followed by formation of a tributylstannyl ether and heating afforded the desired dihydropyrans. The 1,5-diols could also be cyclized to dihydropyrans through a direct cyclodehydration reaction with phosphonium salts, but the enantioselectivities obtained in the reactions were low. The newly developed 1,5-diol methodology was applied to the synthesis of the natural product amphidinol 3. Amphidinol 3 contains three repeating 1,5-diol units and two tetrahydropyran rings. The C1--C25 fragment of amphidinol was synthesized using the 1,5-diol methodology. A dihydropyran which could serve as a precursor to the tetrahydropyranyl units in AM3 was also synthesized from a 1,5-diol. However, the synthetic route to the dihydropyran was not efficient because of mismatched double allylborations using chiral aldehydes.