Rules for ring closure: application to intramolecular aldol condensations in polyketonic substrates

Abstract

An extension of the nomenclature for classifying ring closures to include intramolecular reactions of enolate anions is described, and the rules governing such cyclizations are enumerated. The syntheses of the polyketonic substrates 4-acetyl-2,6-heptanedione ( 11), 4-acetyl-4-methyl-2,7-octanedione ( 24), and 3-acetyl-3-methyl-1,6-diphenyl-1,6-heptanedione ( 33) were carried out, and their base-induced intramolecular aldol condensations studied. With each substrate a favored 6-(enolendo)-exo-trig cyclization to produce cyclohexenone products was the only ring forming reaction observed, this process predominating in all instances over competing disfavored 5-(enolendo)-exo-trig closures, and also over other competing favored cyclizations. The identity of the cyclization product 12 derived from 11 was confirmed by aromatizing 12 to 17, and alternately synthesizing 17 from 3-bromo-5-methylphenol.