2-ALKOXY-3-OXOALKYL-TETRAHYDROPYRANS AND 2-ALKOXY-3-OXOALKYL-TETRAHYDROFURANS - VERSATILE INTERMEDIATES IN HETEROCYCLIC SYNTHESIS

A new Lewis acid-catalysed Michael-type addition of heterocyclic enol ethers to hemiacetal vinylogues 1 or to enones in the presence of a hydroxylic compound is described. The 1,5-keto acetals 3 so obtained have been studied with a view to synthetic applications. Acidic hydrolysis of compounds 3 leads in most cases to annulation products 9 in a stereocontrolled manner. Organometallic addition, hydride reduction or reductive amination of 1,5-keto acetals 3 afford, in good yields, the hydroxy acetals 12 (and cyclisation products 13) and amino acetals 18, respectively. Acidic treatment of these compounds gave access to oxa- and aza-annulation products 13, 17 and 19 by an efficient kinetically controlled heterocyclisation process. These products can be obtained with high cis-junction selectivities as established by NMR spectroscopy and confirmed by equilibration studies.