Recent Advances in Azlactone Transformations

Abstract

Azlactones, also known as oxazolones, are versatile building blocks in organic synthesis due to the presence of multiple pro‐nucleophilic and electrophilic reactive sites. Recently, several elegant organo‐ and metal‐catalyzed studies have been described, allowing the stereocontrolled access to complex structures in only one or a few chemical steps. Moreover, the development of one‐pot, tandem and domino reactions greatly enhanced the azlactone scaffold potential. In this context, this review aims to cover novel methodologies, including a brief overview of oxazolones and Erlenmeyer azlactones preparation. New approaches towards classical reactions, such as dynamic kinetic resolution, cycloadditions, and conjugate additions will be presented as well as new methodologies involving photochemical and flow chemistry technology. Finally, for most studies, selected examples will be presented and mechanistic pathways and/or activating modes will be carefully discussed.

5-(4H)-Oxazolones and Their Benzamides as Potential Bioactive Small Molecules

“…Oxazolones are heterocyclic compounds which can be used as versatile building blocks in organic synthesis, as they contain numerous reactive sites allowing a diversity of possible modifications. Their reactivity (nucleophilic attack to the carbon atom at position 5 of the oxazolone ring) makes them excellent substrates for the synthesis e.g., of enol acetate and benzoxazinone derivatives, phenylpyruvic acid, imidazolinones, amino acids and triazinones [ 21 , 22 ].…”

Stereodivergent entry to β-branched β-trifluoromethyl α-amino acid derivatives by sequential catalytic asymmetric reactions

“…We initially surmised that such substrate-bias, hindering access to syn - 4 , 19 would be circumscribed to the tertiary amine promoted alcoholytic ring-opening. Since a variety of DKRs of azlactones by ring-opening reactions, using different nucleophiles and catalytic approaches (Lewis bases, Lewis acids, Brønsted acids, enzymes), are available in the literature, 14 we hoped that one of these could be subdued to our aims.…”

“…9a ) with Hantzsch esters 12 sets the absolute configuration of the trifluoromethylated β-centre. 13 Subsequent dynamic alcoholytic ring-opening 14 of intermediates 3 fixes the absolute configuration of the α-carbon. In the ring-opening reaction, the substrates 3 feature a considerable bias towards the formation of anti -isomers 4 .…”

Mechanism and Origin of Stereoselectivity in Chiral Phosphoric Acid‐Catalyzed Aldol‐Type Reactions of Azlactones with Vinyl Ethers

“…[7a] When followed by the ring openingo ft he azlactone unit, this reaction provides accesst ob iologically and pharmaceuticallyi ntriguing b-hydroxy-a-aminoa cid derivatives in enantioenriched forms. [7,8] However, the precise reaction mechanism and the origin of the high enantio-and diastereoselectivity have remained unclear. In addition, the stereoselectivity is intriguingly dependent on substituent Ar at the 2-position of the azlactone, [7a, 9] even thought he substituent is introduced at the far side from the reactionsite that is the 4-position of the azlactone.…”