Trimethylsilyl triflate catalysed Diels-Alder reaction of TMS ethers of conjugated dienols with cyclic enones: Evidence for an endo transition state, and first application to synthesis of enantiopure octalins

Abstract

The AlCl 3 catalysed ‘ionic’ Diels-Alder (DA) reaction of 6-methyl-2-cyclohexenones with 3,5-hexadien-1-ol in dichloromethane gives a trans-fused octalin hemiacetal with a β-equatorial methyl group and an axial hydroxyl. In contrast, trimethylsilyl triflate (TMSOTf, 5 mol%) at −20 °C in acetonitrile catalyses the DA reaction to give the trans-fused adduct acetal, whose controlled hydrolysis gives the hemiacetal with an α-axial methyl group. The adduct is thereby differentiated from the AlCl 3 DA adduct, and may be converted into the latter by treatment with p-toluenesulfonic acid in aqueous THF or by AlCl 3 in dichloromethane. In similar fashion, TMSOTf provides full acetal adducts from 2-cyclohexenone, 2-cycloheptenone and methyl vinyl ketone. The optically active enone acetal derived from (1 R,2 R)-1,2-diphenyl-1,2-ethanediol and 2-cyclohexenone gives a racemic acetal adduct derived from the TMS ether of hexadienol. The TMS ether of a mixture enriched in the 3 E-isomer of (2 R,5 E)-2-methyl-3,5-heptadien-1-ol in acetonitrile containing TMSOTf (10 mol%) at −20 °C with 6-methyl-2-cyclohexenone gives the trans-fused acetal adduct, hydrolysis which provides the corresponding octalin hemiacetal as a single enantiomer. Similarly, the mixture enriched in the 3 E-isomer of (2 S,5 E)-2-methyl-3,5-heptadienol TMS ether is converted by way of the octalin acetal into the octalin hemiacetal, enantiomeric with the foregoing product. The reactions are thereby shown to proceed via endo transition states.