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.

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). This hydroxy-directed amidation shows excellent chemoselectivity and is applicable to gram-scale drug synthesis.

The first successful example of the direct synthesis of Weinreb amides using catalytic hydroxy-directed dehydrative amidation of carboxylic acids using diboronic acid anhydride catalyst is described. The methodology is applicable...

An efficient method for the direct synthesis of Weinreb amides derived from serine and threonine derivatives via diboronic acid anhydride-catalyzed hydroxy-directed amidation is described. This is the first successful example of the synthesis of serine- or threonine-derived Weinreb amides using catalytic dehydrative amidations. The methodology could be applied to the concise synthesis of Garner’s aldehyde.

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. The utility of this protocol has been demonstrated by synthesizing natural products, phomamide and Cyclo(Deala-L-Leu).