Organocatalytic Asymmetric Formal [3 + 2] Cycloaddition with in Situ-Generated N-Carbamoyl Nitrones

A novel organocatalytic formal [3 + 2] cycloaddition reaction with in situ generation of N-carbamoyl nitrones is presented. For the first time, N-Boc- and N-Cbz-protected isoxazolidines have been directly obtained as single diastereoisomers in generally high yields and enantiomeric excesses using mild reaction conditions and inexpensive, readily available Cinchona alkaloid quaternary ammonium salts as catalysts. Synthetic manipulations of the products provided highly valuable building blocks such as free isoxazolidines, a N-Boc-1,3-aminoalcohol, and a free delta-lactam. This report represents a pioneering work in the use of N-carbamoyl nitrones as electron-poor 1,3-dipoles and glutaconates as new dipolarophiles in asymmetric catalysis.