Three-step assembly of 4-aminotetrahydropyran-2-ones from isoxazoline-2-oxides

摘要

Tetrahydropyran-2-ones with a 4-amino function connected to a tertiary carbon atom – a widely naturally occurring fragment – are constructed by a three step protocol from easily available isoxazoline 2-oxides. In the first stage, the carbon skeleton of the target product is formed upon a C,C-coupling of a silyl ketene acetal with a nitronate function, under silyl triflate catalysis. The key step of the assembly consists of the oxidative cleavage of an endocyclic N–O bond of intermediate cyclic nitroso acetals with m CPBA, accompanied with lactone ring closure, and gives rise to β-nitro-δ-lactones in 63–85% yields. The latter are reduced with amalgamated aluminium, to furnish the target scaffold.