Azlactones (also known as oxazolones) are heterocycles usually employed in the stereoselective synthesis of α,α-amino acids, heterocycles and natural products. The versatility of the azlactone scaffold arises from the numerous reactive sites, allowing its application in a diversity of transformations. This review aims to cover classical and recent applications of oxazolones, especially those involving stereoselective processes. After a short introduction on their structures and intrinsic reactivities, dynamic kinetic resolution (DKR) processes as well as reactions involving stereoselective formation of a new σ C-C bond, such as alkylation/allylation/arylation, aldol, ene, Michael and Mannich reactions will be exposed. Additionally, cycloadditions, Steglich rearrangement and sulfenylation reactions will also be discussed. Recent developments of the well-known Erlenmeyer azlactones will be described. For the most examples, the proposed mechanism, activation modes and/or key reaction intermediates will be exposed to rationalize both the final product and the observed stereochemistry. Finally, this review gives an overview of the synthetic utility of oxazolones.
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.
The first report of the preparation of symmetric and nonsymmetric diaminotruxinic derivatives through the photoredox [2 + 2] cycloadditions of Erlenmeyer azlactones is described, affording the desired compounds in high regio-and diastereocontrol (only head-to-head coupling). Mechanistic studies by DFT suggest that the reaction proceeds through a neutral photocatalytic pathway.
Azlactones
are versatile heterocycles employed in a diversity of
transformations; the main drawback of these cycles consists in the
epimerization of the α-carbonyl stereocenter during its preparation.
We hereby present a theoretical study to explain how the racemization
occurs. Two hypotheses were investigated: the keto–enol tautomerism
and the base-mediated racemization, through an enolate intermediate.
The results showed that the latter is consistent with the experimental
data and can spontaneously occur at room temperature. The same pathway
was evaluated for 2-alcoxy azlactone, showing a slower epimerization
ratio, consistent with the literature data.
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