Re-evaluation of P-Chiral, N-Phosphoryl Sulfonamide Brønsted Acids in the Asymmetric Synthesis of 1,2,3,4-Tetrahydroquinoline-2-carboxylate Esters via Biomimetic Transfer Hydrogenation

Abstract

AbstractEnantioenriched heterocyclic and rigidified bioisosteres of amino acids are valuable building blocks in drug discovery, particularly in the design of peptidomimetic drugs. The rigidified bioisostere of phenylalanine, 1,2,3,4-tetrahydroquinoline-2-carboxylic acid, is found in several biologically active compounds. However, only a small number of successful methodologies have been reported for its asymmetric synthesis. To develop an environmentally benign and metal-free organocatalytic process for the preparation of this compound, a number of novel P-chiral, N-phosphoryl sulfonamide Brønsted acids were synthesized and evaluated in a biomimetic transfer hydrogenation reaction of quinoline-2-carboxylates to give the (R)-1,2,3,4-tetrahydroquinoline-2-carboxylates.