Synthesis of Nitrogen Heterocycles via Ring Expansion of 3-Oxetanone-derived Spirocycles

Carreira et al. have reported the synthesis of saturated nitrogen heterocycles via ring expansion of 3-oxetanone-derived spirocycles. According to their results, 3-oxetanone readily undergoes condensation with β-heteroatom-substituted amino compounds to form related spirocycles 3. Subsequent ring expansion of 3 proceeds by the treatment with In(OTf)₃ as a Lewis acid in the presence of TMSCN, affording the corresponding saturated nitrogen heterocycles 4 with excellent diastereoselectivity. This reaction is broad in scope and provides convenient access to valuable morpholines, thiomorpholines, and piperazines relevant to drug discovery.