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

Abstract

Synthesis of β-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-2yne-1,5-diols and Michael acceptors as an efficient route for the synthesis of βhydroxyenones with excellent yields and high regioselectivity. The β-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.

Gold(I)-Catalyzed Synthesis of Heterocycles via Allene Oxide from Propargylic Alcohols

“…Initially, a series of N-protected 5-aminopent-2-yn-1-ols were prepared following the available literature process. , With these starting materials in hand, efforts were initiated to establish the generation of pyrrole ( 2a ) from the available propargyl alcohol ( 1a ) (Table ). In this way, substrate 1a was subjected to various conditions.…”

“…The title compound was isolated as a light yellow liquid [literature procedure: eluent petroleum ether:EtOAc, 217 mg, 1.135 mmol, 83%;].…”

“…1-Phenylhex-3-yne-1,5-diol (1ae). 17 The title compound was isolated as a light yellow liquid [literature procedure: 17 eluent petroleum ether:EtOAc, 217 mg, 1.135 mmol, 83%;]. Synthesis of N-Protected 2,5-Disubstituted-1H-pyrroles (2).…”