Bi(OTf)₃-catalyzed three-component synthesis of α-amino acid derivatives

Abstract

A highly efficient Bi(OTf)3-catalyzed multicomponent synthesis of arylglycines from readily available starting materials is described. The reaction proceeds under mild conditions and provides a general route to various N-protected arylglycines.

Bi(OTf)3-Catalyzed Multicomponent α-Amidoalkylation Reactions

“…7 However, most common procedures require stoichiometric amounts of Lewis or Brønsted acids 8 or are limited to the reaction of electron-rich aromatics and heteroaromatics, such as indole and naphthol. [9][10][11][12] Our interest in developing novel multicomponent reactions for the rapid synthesis of pharmaceutical active molecules [13][14][15] has led us to closer examination of these threecomponent reactions. In the course of our investigations, we were able to develop a Bi(OTf) 3 -catalyzed three-component reaction between amides, formaldehyde and arenes.…”

“…Analytical data are consistent with literature. 41 N-(2-Methyl-1-propen-1-yl)benzamide (14). Compound 14 was isolated during the attempted preparation of N-(2-methyl-1- (2,4,6trimethylbenzyl)propyl)benzamide.…”

“…Our interest in developing novel multicomponent reactions for the rapid synthesis of pharmaceutically active molecules − has led us to a closer examination of these three-component reactions. In the course of our investigations, we were able to develop a Bi­(OTf) 3 -catalyzed three-component reaction between amides, formaldehyde, and arenes.…”

Palladium-Catalyzed Enantioselective Three-Component Synthesis of alpha-Arylglycine Derivatives from Glyoxylic Acid, Sulfonamides and Aryl Trifluoroborates

“…Consequently, examples for asymmetric version of the Petasis-Borono-Mannich reaction are rare [13] and usually rely on the utilization of chiral amine components in stoichiometric amounts. [10,11] As part of our research program utilizing the in situ generation of reactive imine species, we have disclosed iron-and bismuth-catalyzed three-component reactions for the synthesis of -aryglycines [14][15][16] , in which the aryl boronic acid could be replaced with an electron-rich (hetero)arene as nucleophile. In parallel, we have developed palladium-catalyzed three-component reactions between aryl boronic or carboxylic acids, amides or sulfonamides and different aldehyde components as attractive and broadly applicable alternative to the classical Petasis-Borono-Mannich reaction (Scheme 1b).…”

Palladium-Catalyzed Enantioselective Three-Component Synthesis of α-Substituted Amines

“…Based on our previous research on acylimine-based three-component reactions for the preparation of α-substituted amides and amino acids, we expected to perform the more challenging, asymmetric version by using an appropriate chiral catalyst. First, encouraging results were obtained with p -toluenesulfonamide as the amide component.…”