Sc(OTf) ₃ -Catalyzed Diastereoselective [3 + 3] Cycloaddition of Chiral Bicyclo[1.1.0]butanyl Imides and Nitrones

A chiral-auxiliary-induced asymmetric synthesis of 2-oxa-3-azabicyclo[3.1.1]heptanes is described. This approach employs a new class of chiral bicyclo[1.1.0]butanes incorporating an (S)-4-benzyl-2-oxazolidinone auxiliary as the key chiral controller. The Sc(OTf)3-catalyzed [3 + 3] cycloaddition of nitrones proceeds smoothly in up to 98% yield with moderate to excellent diastereoselectivities (up to >20:1 dr) across 49 examples. The DFT calculation results are consistent with favorable nucleophilic attack on the Re face of the nitrone, leading to the generation of the S-configured chiral center. The calculated activation energy of the key transition state is 3.8 kcal/mol, in agreement with the excellent diastereoselectivity.