Tandem 1,3-Dipolar Cycloaddition/Rearrangement of Nitronates with Cyclooctyne for the Diastereoselective Synthesis of Spiroaziridine Derivatives

The 1,3-dipolar cycloaddition of cyclic nitronates (5,6-dihydro-4<i>H</i>-1,2-oxazine <i>N</i>-oxides) with cyclooctyne affords oxazine-annulated spiroaziridine derivatives in mild conditions with high yields and diastereoselectivity via consecutive strain-promoted [3 + 2]-cycloaddition/ring contraction. Isoxazoline <i>N</i>-oxides and silyl nitronates also react smoothly, albeit with a lower diastereoselectivity. DFT calculations reveal key features, such as half-boat conformation of the oxazine ring during cycloaddition, and control of the stereoselectivity during ring contraction by an anomeric effect in the O-N-O moiety.