Stereoselective Synthesis of Oxacycles via Ruthenium-Catalyzed Atom-Economic Coupling of Propargyl Alcohols and Michael Acceptors

Synthesis of beta-hydroxyenones and its application toward development of tetrahydro-4H-pyran-4-one in an atom-economic fashion is limited. This manuscript describes a ruthenium-catalyzed atom-economic coupling of pent-2-yne-1,5-diols and Michael acceptors as an efficient route for the synthesis of beta-hydroxyenones with excellent yields and high regioselectivity. The beta-hydroxyenones further undergo a 6-endo trig cyclization under acid-catalyzed conditions to deliver the tetrahydro-4H-pyran-4-ones with high diastereoselectivity. An intramolecular aldol condensation under mild basic conditions and palladium-catalyzed oxidative aromatization was developed for the synthesis of hexahydro-6H-isochromen-6-ones and isochromanols, respectively, from highly substituted tetrahydro-4H-pyran-4-ones with excellent yield and diastereoselectivity. Overall, this work demonstrates the synthetic potential toward the synthesis of oxacycles like tetrahydro-4H-pyran-4-ones, hexahydro-6H-isochromen-6-ones, and isochromanols via an atom-economic catalysis.

Automated summary

The manuscript describes a ruthenium-catalyzed atom-economic coupling method for the synthesis of beta-hydroxyenones, which can further lead to the high-yield and high diastereoselective synthesis of tetrahydro-4H-pyran-4-ones. Through intramolecular aldol condensation and palladium-catalyzed oxidative aromatization, hexahydro-6H-isochromen-6-ones and isochromanols can be synthesized from highly substituted tetrahydro-4H-pyran-4-ones with excellent yield and diastereoselectivity.