Bismuth- and Iron-Catalyzed Three-Component Synthesis of α-Amino Acid Derivatives: A Simple and Convenient Route to α-Arylglycines

Abstract

Efficient bismuth-and iron-catalyzed three-component syntheses of α-arylglycines have been developed. These methods provide a general, atom-economic route to various N-protected α-arylglycines starting from readily available amides (or carbamates), glyoxalates, and (hetero)arenes with water as the only by-product. Scope and limitations of bismuth-and iron-catalyzed reactions are discussed and compared. In addition, mechanistic investigations as well as initial forays into stereoselective three-component reactions are presented.

Synthesis of Diaminoacetic Acid Derivatives as a Promising Scaffold for the Synthesis of Polyheterocyclic Cage Compounds

“…The condensation between the selected amides and ethyl glyoxylate or glyoxylic acid to furnish 2 was explored herein in chloroform, benzene, acetone, toluene, or xylene at reflux, as well as in aqueous medium at room temperature. The selected solvents are most often utilized in this process. − The starting compounds were used in stoichiometric quantities. In all experiments, the resulting water was removed by a Dean–Stark trap to shift the reaction toward the condensation products (the Le Chatelier–Brown principle).…”

“…In addition to protic acids, Lewis acids can be employed as the catalyst. The condensation of substituted carboxamides and sulfonamides takes place in hot nitromethane over iron chloride (III) , or copper chloride (III) and in toluene at reflux over boron trifluoride ethyl etherate . In most cases, syntheses are effected under reflux.…”

Merging Cobalt-Catalyzed C–H Activation with the Mannich Reaction: A Modular Approach to α-Substituted N-Sulfonyl Amines

“…Over the years various improvements and extensions of the classical Mannich reaction to other nucleophiles have been reported. These “Mannich-type” reactions utilize electron-rich (hetero)­arenes or organometallic species as nucleophilic species (Scheme a) . The amino- or amidoalkylation of (hetero)­arenes proceeds via an electrophilic aromatic substitution pathway.…”

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

“…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 α-arylglycines [ 14 – 16 ], in which the arylboronic acid could be replaced with an electron-rich (hetero)arene as nucleophile. In parallel, we have developed palladium-catalyzed three-component reactions between arylboronic 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 ) [ 17 – 21 ].…”