Catalytic Enantioselective [3 + 2] Cycloaddition of α‑Keto Ester Enolates and Nitrile Oxides

An
enantioselective [3 + 2] cycloaddition reaction between nitrile
oxides and transiently generated enolates of α-keto esters has
been developed. The catalyst system was found to be compatible with
in situ nitrile oxide-generation conditions. A versatile array of
nitrile oxides and α-keto esters could participate in the cycloaddition,
providing novel 5-hydroxy-2-isoxazolines in high chemical yield with
high levels of diastereo- and enantioselectivity. Notably, the optimal
reaction conditions circumvented concurrent reactions via O-imidoylation
and hetero-[3 + 2] pathways.