Imine Azaenolates: Synthesis, Reactivity, and Outlook

Abstract

Azaenolates are, quite simply, the aza variant of enolates. Compared to their oxygen counterparts, additional control of the reactivity of azaenolates can be achieved by altering the substituent on the nitrogen atom as well as the metal counterion. Since the seminal examples reported in the early 1960s, azaenolates of various metals have been shown to react with a diverse set of electrophilic partners, including challenging electrophiles such as alkyl fluorides, epoxides, and oxetanes. This review describes in detail the current state of the art of the chemistry of azaenolates derived from imines, with a particular focus on the comparison of the reactivity exhibited with different metal counterions.

Zinc-Mediated C–H Metalations in Modern Organic Synthesis

“…Zinc aza-enolates are predominantly obtained via transmetallation of lithiated species with zinc halides or dialkylzincs, which is a method of limited utility due to poor functional group tolerance. 63 Developing a protocol for a direct and selective synthesis of this moiety under mild conditions would be beneficial and pharmaceutically relevant, especially for functionalisation of common drug scaffolds such as thiadiazoles, pyridines, pyrimidines, triazoles and tetrazoles. 36 Scheme 32 Csp 3 -H zincations using TMP2Zn 4.…”

“…Zinc aza-enolates are predominantly obtained via transmetalation of lithiated species with zinc halides or dialkylzincs, which is a method of limited utility due to poor functional group tolerance. 62 Developing a protocol for a direct and selective synthesis of this moiety under mild conditions would be beneficial and pharmaceutically relevant, especially for functionalisation of common drug scaffolds such as thiadiazoles, pyridines, pyrimidines, triazoles, and tetrazoles. 36 Scheme 32 Csp 3 -H zincations using TMP 2 Zn Another example of a direct Csp 3 zincation was reported by Dalziel, Carrera, and co-workers who worked on a highly diastereoselective -arylation of 3-methyl-3-(triethylsiloxy)cyclobutanecarbonitrile (131) to form cis and trans diastereomers of type 132.…”

Second-Generation Enamine-Type Schiff Bases as 2-Amino Acid-Derived Antifungals against Fusarium oxysporum: Microwave-Assisted Synthesis, In Vitro Activity, 3D-QSAR, and In Vivo Effect

“…In addition, they could be used for carrying out the synthesis of various heterocyclic compounds [ 13 ]. Some reports have shown the use of tandem reactions to obtain this class of intermediates that involve metal catalysts or the use of extremely strong bases such as LDA, butyllithium, or phenyl lithium, which employ severe reaction conditions [ 14 ]. Other methodologies are based on multistep reactions, such as the nucleophilic cleavage of α-amino acetals induced by TMSOTf, which can be used to prepare a wide range of substituted 1,2-amino ethers [ 15 ].…”