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An efficient asymmetric synthetic approach for the synthesis of Cα‐substituted pipecolic acid has been investigated through utilizing an N‐fused bicyclic system. Despite the fluxionality of the pipecolic imidazolidinone, N‐alkylation proceeded in high yield with excellent selectivity. The subsequent [2,3]‐Stevens rearrangement afforded Cα‐substituted pipecolic acid derivatives successfully. The computational study revealed that the diastereoselectivity during N‐alkylation is governed by Curtin‐Hammett kinetics. Take anN‐Fused Bicycle! Asymmetric synthesis of Cα‐substituted pipecolic acid derivatives has been accomplished by employing a nitrogen fused bicyclic system. A N‐alkylation between the bicyclic compound and allylic bromide gave the corresponding ammonium salt selectively based on the Curtin‐Hammett principle. After performing the subsequent [2,3]‐Stevens rearrangement, we could obtain the enantioselective α‐substituted pipecolic acids.

The first asymmetric synthesis and configurational elucidation of (−)-cephalezomine G was achieved. The highly functionalized Cα-substituted proline derivative was prepared from d-proline as the only chiral source via a C → N → C chirality transfer method consisting of stereoselective N-allylation and [2,3]-Stevens rearrangement. The azaspiranic tetracyclic backbone was constructed using ring-closing metathesis and the Friedel–Crafts reaction. Two contiguous hydroxyl groups were introduced in the later stages.

An efficient strategy for the asymmetric synthesis of Cα-tetrasubstituted proline derivatives from proline has been established. A nitrogen-fused bicyclic system was devised to control the stereodynamics of proline. Through N-quaternizations with allylic electrophiles followed by [2,3]-rearrangements, the bicyclic proline system delivered enantioenriched Cα-tetrasubstituted prolines. This strategy was applied to the concise total synthesis of (−)-amathaspiramide F.