Enantioselective Total Synthesis of (−)-α-Kainic Acid

Abstract

An enantioselective total synthesis of (-)-alpha-kainic acid is described. Key steps are an Ir-catalyzed allylic amination with a propargylic amine to provide an enyne and a diastereoselective intramolecular Pauson-Khand reaction. Subsequent steps involve a Baeyer-Villiger reaction, reduction of the resulting lactone, and direct Jones oxidation of a silyl ether.

Sequential Two‐Step Stereoselective Amination of Allylic Alcohols through the Combination of Laccases and Amine Transaminases

“…The chemical preparation of allylic amines has traditionally attracted great attention, due to the presence of this motif in numerous biologically active and natural products . In addition, their versatility in chemical synthesis has been widely demonstrated by their multiple applications for the preparation of valuable nitrogen‐containing organic compounds .…”

Transition Metal Catalyzed Enantioselective Allylic Substitution in Organic Synthesis

“…Additionally, trimethylsilyl cyanide has been successfully used for the cyanation of various allyl carbonates (Scheme 36) [170]. Hydride sources such as LiAlH 4 [171], LiBHEt 3 [39], Bu 3 SnH [172] react as "hard" nucleophiles via transmetallation followed by reductive elimination [173]. Hydride sources such as LiAlH 4 [171], LiBHEt 3 [39], Bu 3 SnH [172] react as "hard" nucleophiles via transmetallation followed by reductive elimination [173].…”

“…An elegant enantioselective total synthesis of (À)-a-kainic acid was recently reported by Helmchen and coworkers (Scheme 51) [172]. A key step for the preparation of the enantiomeric pure synthon 13 was based on an asymmetric allylic amination with a propargylic amine or N,N-diacylamine.…”

First chemoenzymatic synthesis of (+)‐2‐carboxypyrrolidine‐3‐acetic acid, the nucleus of kainoid amino acids

“…Optical rotation was measured at pH 3 for the comparison with lit. 45 [a] 23 D 118.0 (c 0.1, D 2 O); lit. 45…”

“…Although 6 was shown 20 to not retain the kainate-type selectivity, it was recognized as an agonist of the N-methyl-D-aspartate (NMDA) receptor. 19 Whereas several strategies have been proposed for the asymmetric total syntheses of kainoid amino acids 2,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] and other unnatural kainoids, [37][38][39][40][41][42][43][44][45] only a few asymmetric syntheses of optically active 6 with complete control of the stereochemistry have been proposed. [45][46][47][48][49][50] Biotransformations are a powerful tool to control the configuration of chiral centers in stereoselective synthesis, 51 although to our knowledge, this powerful synthetic approach has not been used in the asymmetric synthesis of CPAA 6.…”