Construction of 1,3-Oxazolidines through a Three-Component [3+2] Cycloaddition of Tetrahydroisoquinolines, Aldehydes, and Ethyl Ketomalonate

A chemoselective and diastereoselective
synthesis of fused oxazolidines
was achieved by a three-component cascade reaction of tetrahydroisoquinolines
(THIQs), α,β-unsaturated aldehydes, and diethyl 2-oxomalonate.
Probably due to the reactivity difference between the aldehyde and
the ketone, the reaction proceeded through the condensation of THIQs
with α,β-unsaturated aldehydes and 1,3-dipolar cycloaddition
of the generated azomethine ylide intermediate with 2-oxomalonate.
The key features are easily available starting materials, mild reaction
conditions, broad substrate scope, and high chemo- and diastereoselectivity.