Conia-ene reaction

In organic chemistry, the Conia-ene reaction is an intramolecular cyclization reaction between an enolizable carbonyl such as an ester or ketone and an alkyne or alkene, giving a cyclic product with a new carbon-carbon bond. As initially reported by J. M. Conia and P. Le Perchec, the Conia-ene reaction is a heteroatom analog of the ene reaction that uses an enol as the ene component. Like other pericyclic reactions, the original Conia-ene reaction required high temperatures to proceed, limiting its wider application. However, subsequent improvements, particularly in metal catalysis, have led to significant expansion of reaction scope. Consequently, various forms of the Conia-ene reaction have been employed in the synthesis of complex molecules and natural products. In the late 1960s, the laboratory of chemist Jean-Marie Conia investigated small carbocyclic molecules, specifically as products of ene-type reactions with carbonyls. These efforts culminated in a 1975 review paper titled “The Thermal Cyclisation of Unsaturated Carbonyl Compounds.” In its original manifestation, the Conia-ene reaction comprised the intramolecular cyclization of ε,ζ-unsaturated ketones or aldehydes to functionalized cyclopentanes upon intense heating. The proposed mechanism invoked a six-membered, ene reaction-like transition state in which the enol tautomer reacts concertedly with the pendant alkene. The same conditions were found to give six- and nine-membered rings with the appropriate substrates, although with lower yields and diastereoselectivity. In the case of γ,δ- and δ,ε-unsaturated ketones, equilibrium favored the linear product over the cyclopropane or cyclobutane. Alkynyl ketones were also found to cyclize under thermal conditions, giving a mixture of the conjugated and skipped cyclic enones. Two key drawbacks prevented wider implementation of the initial Conia-ene reaction. First, molecules with additional functional groups were often incompatible with the high temperatures required for conversion.