Synthesis of Diaryl Hydroxyl Dicarboxylic Acids from Amino Acids

Abstract

Herein we report a unique method for preparing diaryl hydroxyl dicarboxylic acids in a diastereospecific manner. The three-component reaction occurs between amino acid, aromatic aldehyde, and primary alcohol in alkaline solutions under microwave-assisted conditions. The dicarboxylic acids are isolated as sodium salts in high yields (up to 77%) by direct precipitation from the reaction solution. The experimental results suggest that the diastereospecificity originates from a [3,3]-sigmatropic rearrangement followed by a sodium-assisted hydride transfer. As further shown, the previously unreported dicarboxylic acids are easily turned into corresponding δ-lactones.

Impact of Microwaves on Organic Synthesis and Strategies toward Flow Processes and Scaling Up

“…Unforeseeable results were recently obtained by Repo et al when the condensation of l -phenylalanine and benzaldehyde was performed in alkaline ethanol under MW irradiation ( Scheme 21 ). 103 A single crystalline compound with the structure of a dicarboxylic acid 36 was isolated and characterized by X-ray crystallography as a racemic mixture of RRR and SSS enantiomers. Intriguingly, both the pyruvic acid derivative and cinnamaldehyde were obtained by means of MW heating wherein the first one was formed by the condensation of an amino acid with benzaldehyde followed by isomerization and hydrolysis, whereas the second one could be synthesized via a Cannizzaro-type reaction followed by aldolic condensation ( Scheme 22 ).…”

Stereospecific Synthesis of Cyclohexenone Acids by [3,3]-Sigmatropic Rearrangement Route

“…Based on X-ray crystallography herein, the reaction proceeds in a diastereospecific manner; stereocenters in 1a are either RR or its enantiomer SS due to the centrosymmetry in the crystal structure (Figure ) (CDCC 2193907). As shown earlier by us, the diastereospecificity in this new synthetic strategy toward chiral cyclohexenones arises from the elemental reaction step, [3,3]-sigmatropic rearrangement …”

“…In our previous work, 25 we successfully utilized [3,3]sigmatropic rearrangement in dicarboxylic acid synthesis from phenylpyruvate and cinnamaldehyde under microwave-assisted conditions from alkaline alcohol solutions (Figure 1a). We report here that the substrate scope can be expanded toward aryl enones, and this subsequently opens a unique synthesis strategy toward substituted cyclohexanones.…”

“…As shown earlier by us, the diastereospecificity in this new synthetic strategy toward chiral cyclohexenones arises from the elemental reaction step, [3,3]-sigmatropic rearrangement. 25…”

Trapping carbamates of α-Amino acids: One-Pot and catalyst-free synthesis of 5-Aryl-2-Oxazolidinonyl derivatives

“…In particular, "tailor-made" α-amino acids have been regarded as essential components of modern medicinal chemistry, and indeed a significant fraction of small molecular drugs comprise amino-acidic residues [16,23]. However, despite the reactivity of α-amino acids has been the subject of a long-time investigation, there is still space for the exciting and extremely worthy discovery of new reaction types [24][25][26][27]. It is well established that α-amino acids (aaNH2) in aqueous solutions reversibly and easily add carbon dioxide to generate the corresponding ammonium carbamates, Equation 1 [28,29].…”