Accelerating Effect Induced by the Structure of α-Amino Acid in the Copper-Catalyzed Coupling Reaction of Aryl Halides with α-Amino Acids. Synthesis of Benzolactam-V8

Abstract

The coupling of optically pure R-amino acids with aryl halides produces enantiopure N-aryl-Ramino acids with retention of configuration under the catalysis of CuI. This reaction can complete at much lower temperature than typical Ullmann condensation even for electron-rich aryl halides, which indicates that an accelerating effect induced by the structure of the R-amino acid exists in this reaction. R-Amino acids with larger hydrophobic groups give higher coupling yields, while those with smaller hydrophobic groups only deliver lower yields and no coupling products were detected for those with hydrophilic groups. No racemization was observed in most cases of this coupling reaction. After some controlled experiments, a possible mechanism including the π-complex and the intramolecular substitution reaction is proposed. Based on this catalyzed reaction, a facile and stereoselective synthesis of benzolactam-V8, a new PKC activator, is achieved.

Modern Synthetic Methods for Copper‐Mediated C(aryl)O, C(aryl)N, and C(aryl)S Bond Formation

“…(22)]. [68] The accelerating affect induced by aamino acids has allowed Ullmann-type condensations to be carried out at temperatures significantly lower than those under classic experimental conditions. A systematic study of a variety of amino acids (Schemes 49-51) as well as different aryl halides and copper ion sources allowed the formation of a wide range of products.…”

A General and Practical Access to Chiral Quinoxalinones with Low Copper‐Catalyst Loading

“…Recently, Ullmann-type coupling reactions [1] using copper as catalyst introduced by Ullmann, [2] Goldberg, [3] Buchwald, [4] Ma [5] and Taillefer [6] are attracting much attention, because of the experimental simplicity, economic points of view, as well as low toxicity and stability of the catalyst. Therefore, various efficient and useful carbon-carbon, carbon-nitrogen, carbon-oxygen, and carbon-sulfur bond forming reactions were developed in recent years.…”

Solvent Dependent Preparation of CuI Nanocrystals and the Catalysis in Sonogashira Coupling Reaction

“…In a typical preparation, Cu(Ac) 2 •H 2 O (0.2 g) and PEG20000 (2 g) were dissolved in 50 mL of distilled water to form a solution; an aqueous mixture (50 mL) of KI (0.34 g) added N 2 H 4 •H 2 O (0.2 mL) was rapidly poured into the freshly prepared solution under stirring. After further stirring for 20 min, centrifugation and washing with distilled water, ethanol and acetone for three cycles respectively, the product was dried at 60 ℃ in an oven to obtain white powder 1 [0.18 g, yield 95% based on Cu(OAc) 2 …”

“…After further stirring for 20 min, centrifugation and washing with distilled water, ethanol and acetone for three cycles respectively, the product was dried at 60 ℃ in an oven to obtain white powder 1 [0.18 g, yield 95% based on Cu(OAc) 2 …”