Carbocyclization of Heterosubstituted Alkynes via the Memory of Chirality: Access to Cα-Substituted Proline Derivatives.

Abstract

An efficient strategy for the asymmetric synthesis of Cα-substituted proline derivatives from acyclic α-amino acids has been established. The 5-exo-dig asymmetric cyclization of α-amino ester enolates onto heterosubstituted alkynes provided a product with excellent enantioselectivity via the memory of chirality concept. Density functional theory calculations indicated that a heteroatom is crucial for the success of the asymmetric cyclization because a more stabilized vinyl carbanion is produced. This new method has the potential to enable the rapid asymmetric construction of bioactive molecules containing the pyrrolidine skeleton.