Thermal and metal-catalyzed cyclization of 1-substituted 3,5-dien-1-ynes via a [1,7]-hydrogen shift: Development of a tandem aldol condensation- dehydration and aromatization catalysis between 3-en-1-yn-5-al units and cyclic ketones

Abstract

This work investigates the feasibility of thermal and catalytic cyclization of 6,6-disubstituted 3,5-dien-1-ynes via a 1,7-hydrogen shift. Our strategy began with an understanding of a structural correlation of 3,5-dien-1-ynes with their thermal cyclization efficiency. Thermal cyclization proceeded only with 3,5-dien-1-ynes bearing an electron-withdrawing C(1)-phenyl or C(6)-carbonyl substituent, but the efficiencies were generally low (20-40% yields). On the basis of this structure-activity relationship, we conclude that such a [1,7]-hydrogen shift is characterized by a "protonic" hydrogen shift, which should be catalyzed by π-alkyne activators. We prepared various 6,6-disubstituted 3,5-dien-1-ynes bearing either a phenyl or a carbonyl group, and we found their thermal cyclizations to be greatly enhanced by RuCl 3, PtCl2, and TpRuPPh3(CH3CN) 2PF6 catalysts to confirm our hypothesis: the C(7)-H acidity of 3,5-dien-1-ynes is crucial for thermal cyclization. To achieve the atom economy, we have developed a tandem aldol condensation-dehydration and aromatization catalysis between cycloalkanones and special 3-en-1-yn-5-als using the weakly acidic catalyst CpRu(PPh3)2Cl, which provided complex 1-indanones and α-tetralones with yields exceeding 65% in most cases. The deuterium-labeling experiments reveal two operable pathways for the metal-catalyzed [1,7]-hydrogen shift of 3,5-dien-1-ynes. Formation of α-tetralones d4-56 arises from a concerted [1,7]-hydrogen shift, whereas benzene derivative d4-9 proceeds through a proton dissociation and reprotonation process. © 2006 American Chemical Society.