Organoboron catalysis for direct amide/peptide bond formation.

Amides and peptides are ubiquitous functional groups found in several natural and artificial materials, and they are essential for the advancement of life and material sciences. In particular, their relevance in clinical medicine and drug discovery has increased in recent years. Dehydrative condensation of readily available carboxylic acids with amines is the most "direct" method for amide synthesis; however, this methodology generally requires a stoichiometric amount of condensation agent (coupling reagent).

Concise Synthesis of 2,5-Diketopiperazines via Catalytic Hydroxy-Directed Peptide Bond Formations.

2,5-Diketopiperazines (DKPs) with hydroxymethyl functional groups are essential structures found in many bioactive molecules and functional materials. We have established a simple protocol for the concise synthesis of this type of DKPs through diboronic acid anhydride-catalyzed hydroxy-directed peptide bond formations. The sequential reactions in this report, which consist of three steps, an intermolecular catalytic condensation reaction in which water is the only byproduct, a simple deprotection of the nitrogen-protecting group, and an intramolecular cyclization, enabled the synthesis of functionalized DKPs in high to excellent yields without any intermediate purification.

Diboronic Acid Anhydride-Catalyzed Direct Peptide Bond Formation Enabled by Hydroxy-Directed Dehydrative Condensation.

We report the catalytic direct peptide bond formations via dehydrative condensation of β-hydroxy-α-amino acids, affording the serine, threonine, or β-hydroxyvaline-derived peptides in high to excellent yields with high functional group tolerance, minimum epimerization, and excellent chemoselectivity. The key to the success of these atom-economical transformations is the use of diboronic acid anhydride catalyst for the hydroxy-directed reactions.

Synthesis of Weinreb amides using diboronic acid anhydride-catalyzed dehydrative amidation of carboxylic acids.

The first successful example of the direct synthesis of Weinreb amides using catalytic hydroxy-directed dehydrative amidation of carboxylic acids using the diboronic acid anhydride catalyst is described. The methodology is applicable to the concise syntheses of eight α-hydroxyketone natural products, namely, sattabacin, 4-hydroxy sattabacin, kurasoins A and B, soraphinols A and B, and circumcins B and C.

Diboronic Acid Anhydrides as Effective Catalysts for the Hydroxy-Directed Dehydrative Amidation of Carboxylic Acids.

The direct catalytic dehydrative amidation of β-hydroxycarboxylic acids with amines is described. A biphenyl-based diboronic acid anhydride with a B-O-B skeleton is shown to be an exceptionally effective catalyst for the reaction, providing β-hydroxycarboxylic amides in high to excellent yields with a low catalyst loading (minimum of 0.01 mol %, TON up to 7,500).