Catalytic Asymmetric Tandem Reaction of Tertiary Enamides: Expeditious Synthesis of Pyrrolo[2,1-a]isoquinoline Alkaloid Derivatives.

Abstract

Reported is a new and efficient strategy for rapid construction of the chiral tetrahydropyrrolo[2,1-a]isoquinolin-3(2H)-one structure from unique tertiary enamide synthons. A Cu(OTf)2 /chiral Pybox complex catalyzes the intramolecular enantioselective addition of tertiary enamides to ketonic carbonyls with subsequent diastereoselective interception of the resulting acyliminium by tethered electron-rich aryl moiety. The tandem reaction produces diverse tetrahydropyrrolo[2,1-a]isoquinolin-3(2H)-one derivatives as the sole diastereoisomers in good to excellent yields with up to 98.5 % ee. The transformations of the resulting heterocycles into various hexahydropyrrolo[2,1-a]isoquinoline derivatives were also demonstrated. The cyclization products, which are difficult to obtain by other synthetic means, are structural motifs found in many bioactive alkaloids.