Conformationally Restricted Carbocyclic γ-Amino Acids: Synthesis of Diastereomeric 3-Amino-5-arylcyclopentane 1-Carboxylic Acids

Abstract

A Trost Pd-catalyzed [3+2] cycloaddition between a p-benzyloxy cinnamate bearing an Evans auxiliary and 1-trimethylsilyl-2-acetoxymethylpropene is disclosed leading to, after functional group manipulation, previously unreported diastereoisomeric 3-amino-5-arylcyclopentane 1-carboxylic acids via the corresponding 3-hydroxy and 3-azido precursors. The availability of these conformationally restricted cyclic amino acids may find utility in the context of CNS-active compounds related to GABA, or as peripheral units of bioactive pharmaceuticals. An expedient alternative 4-step synthesis of 3S-amino-5S-p-hydroxyphenyl-1S-cyclopentane carboxylic acid methyl ester was achieved starting with the (–)-Vince lactam and utilizing a regio- and diastereoselective Pd-catalyzed hydroarylation reaction.

Key words

GABA - γ- amino acid - [3+2] cycloaddition - Vince lactam - hydroarylation - conformational restriction

Publication History

Received: 09 May 2023

Accepted after revision: 10 July 2023

Article published online:
04 September 2023

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