Summary of the technology
Synthesis of Heterocycles via Controlled Cyclization of Alpha-Enaminones
Project ID : 6-2016-4351
Description of the technology
α-enaminone, heterocycles, cyclization
Current development stage
General list: TRL2Technology Concept Formulated
- Oxazine, azaspirone, quinolines, quinolinone, and quinolinol structures are frequently observed as scaffold segments in various biochemical compounds. These architectures have been identified as building blocks of a numerous alkaloids and often remotely related metabolites.
- Unfortunately, access to a large number of these target molecules, and their structural analogues, is either unknown or hindered by the multistep syntheses.
- An in-depth analysis of the introduced cores suggests that α-enaminone scaffold of Type-1 has the potential to serve as an operational, collective key unit for their construction via controlled intramolecular cyclizations.
- However, little is known about α-enaminones, apparently because they are often not directly accessible from the corresponding diketones. Furthermore, methods for the preparation of heterocycles using α-ketoenamines are limited.
A novel methodology for the synthesis of heterocycles via controlled cyclization of an easily accessible α -Enaminones common key precursors
- Linking simple and single enaminone core with a diverse, heterocyclic architectures.
- Unexplored, stable α-enaminone synthones, radically different from other known α- or β-counterparts by their chemical behavior.
- Unlock unusual functionalities of -enaminone synthones.
- Accurate design of the starting material allows specific and selective functionalization reactions across the unsaturated scaffold, enabling the preparation of diverse products.
- α-enaminones can react as enamines (nucleophiles), as well as α,β-unsaturated ketones (electrophiles).
- Our finding uncovers unprecedented reactivity of α,β-unsaturated enaminones driven by their “dual electronic attitude”
- The feasibility of this new concept is demonstrated in the direct functionalization of enaminone precursors, such as alkylation; 1,2- 1,3-, or 1,4-addition; and C−O bond formation.
- It was successfully demonstrated that readily available α-enaminone precursors undergo facile cyclizations under basic conditions to afford a broad spectrum of heterocycles, such as azaspirones, quinolinones, quinolines, quinolinols, and oxazines.
Fig.1 : New α- enaminone synthone
Fig.2 : Dual electronic attitude of α- enaminone
- Collective synthesis of several important classes of heterocycles.
- A potential application for the construction of highly complex systems.
- Paves the way for novel retrosynthetic pathways in the field of chemical research.