Lewis Acid Catalysed [4+2] Heterocycloadditions between Ketone Enol Ethers and β-Ethylenic α-Oxo Esters

Abstract

The [4+2] heterocycloaddition reaction between (E)-γ-substituted β-unsaturated α-oxo esters 1a−d and cyclic and acyclic ketone enol ethers 2a−l afforded heteroadducts 3−5 in high yields when either [Eu(fod)3] or SnCl4 were used as the catalyst. With methyl (E)-benzylidenepyruvate (1a), the two catalytic modes displayed divergent stereoselectivities. In the case of the heterocycloaddition of silyl enol ether 2h, X-ray investigations established the relative configurations of the bicyclic adducts 3h and 5h, each obtained as the major isomer with [Eu(fod)3] and with SnCl4, respectively. These assignments provided valuable information concerning the concerted vs. nonconcerted mechanism of these acid-catalysed reactions. With methyl (E)-tert-butoxymethylenepyruvate (1d), the scope of the reaction proved to be restricted to alkyl enol ethers as the dienophiles. In this case, the stereochemical process followed a different pathway, exemplified by the X-ray structure of the adduct 4q, obtained with total stereoselectivity from 1d and 1-methoxycyclohexene (2f) when SnCl4 was the catalyst.