Oxazolones in Organocatalysis, New Tricks for an Old Reagent

Abstract

Oxazolones or azlactones are among the most-common starting materials for the synthesis of quaternary amino acids. Since the seminal works of Steglich and co-workers until the recent examples from Ooi and co-workers, azlactones have been the focus of intense research. Oxazolones are also widely used in organometallic chemistry; however, with the "renaissance" of organocatalysis, this reagent has emerged as an important starting material for a broad range of new organocatalytic asymmetric methodologies. In this Focus Review, we aim to cover all of these new organocatalytic methodologies. We begin by discussing the dynamic kinetic resolution reactions developed with azlactones. Then, we disclose the organocatalytic rearrangements. Finally, we focus on the use of oxazolones as nucleophiles in organocatalytic processes.

Coinage metal complexes as chiral catalysts for 1,3-dipolar cycloadditions

“…Unfortunately, the reaction to give 22 did not work when phosphoramidite·AgX complexes were employed.At this moment, studies concerning the synthesis of the most active third generation antiviral agent 30 (GSK625433) are underway using imino ester 36 as starting precursor of the corresponding azomethine ylide (Figure 8) [65]. Such as it was described at the beginning of this section, oxazol-5-(4H)-ones (azlactones) are suitable heterocycles to perform this C-C bond generation based strategy affording both quaternized and non quaternized α-amino acid derivatives [67,68,69,70]. These substrates can be easily transformed in münchnones, which are potential 1,3-dipoles, after deprotonation and imine-activation with a chiral Lewis acid.…”

Multicomponent synthesis of 4-arylidene-2-phenyl-5(4H)-oxazolones (azlactones) using a mechanochemical approach

“…4-Arylidene-2-phenyl-5(4H)oxazolones, which are also known as azlactones, are important intermediates in the synthesis of several small molecules, including amino acids [20–23], peptides [24, 25], 2,2-disubsituted-2H-oxazol-5-ones with total region and stereo control [26]. Compounds belonging to this structural class may also be used as precursors for other heterocyclic systems [27].…”

Organocatalytic asymmetric approach to spirocyclic tetrahydrothiophenes containing either a butenolide or an azlactone structural motif

“…[19][20][21][22][23][24] Notably, the azlactone moiety serves as a synthetic precursor of α,α-disubstituted amino acid and the azlactone ring opening can be accomplished under acidic conditions. [25][26][27][28][29][30][31] Given the importance of tetrahydrothiophene, butenolide and azlactone scaffolds, the development of methods for their introduction into target molecules, in particular in a stereocontrolled manner, constitutes an important goal in modern synthetic organic chemistry. Herein we report our studies on the development of an organocatalytic strategy leading to spirocyclic tetrahydrothiophenes 7 and 8 bearing a butenolide or azlactone structural motif (Scheme 1).…”