Asymmetric Cα‐Alkylation of Pipecolic Acid via Curtin‐Hammett Controlled Diastereoselective N‐Alkylation. Issue 7 (21st June 2019)

• Record Type: Journal Article
• Authors: Cho, Hyunkyung; Jung, Jaehyun; Kim, Jinju; Park, Soojun; Kim, Sanghee
• Is Part Of: Asian journal of organic chemistry. Volume 8:Issue 7(2019)
• Page Start: 1010
• Page End: 1016
• Publication Date: 2019-06-21
• Subjects: pipecolic acid -- nitrogen heterocycles -- chirality -- Curtin-Hammett principle -- bicyclic systems; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; 547.005
• DOI: 10.1002/ajoc.201900220
• Languages: English
• ISSNs: 2193-5807

Abstract

Abstract: 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. Abstract : Take an N ‐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.