The Wonderful World of β‐Enamino Diketones Chemistry

Abstract

The simple preparation and functionalization of oxa/aza heterocycles requires new and efficient starting materials to be discovered so that regioselective methodologies with a wide range of applications in organic synthesis can be developed. With this in mind, β‐enamino diketones have emerged as a suitable building block for preparing the most diverse (poly)heterocyclic systems, through cyclocondensation or cycloaddition reactions. This review compiles all the reactions that have been conducted using these starting materials, ever since they were first disclosed in 1980.

Design, Synthesis, and Cholinesterase Inhibitory Activity of 4‐Substituted‐6‐(trihalomethyl)‐2‐methylsulfanyl Pyrimidines

“…[16] Given the high chemoselectivity that has been observed in the synthesis of several heterocycles, the use of these enones in heterocyclic synthesis is now well established. [17][18][19][20][21] The use of cholinesterase inhibitors-acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)-in Alzheimer's disease treatment has been widely reported, because their action leads to increases in the synaptic levels of the neurotransmitter acetylcholine (ACh). [22][23][24] Thus, the continuing search for new AChE and BChE inhibitors has an important role in medicinal chemistry.…”

“…On the other hand, allylic brominated β‐alkoxyvinyl trihalomethyl ketones (enones) have been far less explored in heterocyclic synthesis, especially in regard to pyrimidines [16] . Given the high chemoselectivity that has been observed in the synthesis of several heterocycles, the use of these enones in heterocyclic synthesis is now well established [17–21] …”

Synthesis of Highly Functionalized 4-Amino-2-(trifluoromethyl)-1H-pyrroles

“…18 Over the last few years, our research group has been demonstrating the versatility of 4-alkoxy(or amino)vinyl trihalomethyl ketones in the synthesis of pyrimidines, [19][20][21] tetrahydropyridines, 22 1,4-diazacycles, 23 and several other compounds. 13,24,25 Scheme 1 Selected approaches for the synthesis of 1H-pyrroles from 5azido/bromo enones…”

“…18 Over the last few years, our research group has been demonstrating the versatility of 4-alkoxy(or amino)vinyl trihalomethyl ketones in the synthesis of pyrimidines, [19][20][21] tetrahydropyridines, 22 1,4-diazacycles, 23 and several other compounds. 13,24,25 Scheme 1 Selected approaches for the synthesis of 1H-pyrroles from 5azido/bromo enones Several strategies for the synthesis of (trifluoromethyl)pyrroles have been reported using the most diverse starting materials; [26][27][28] however, a search of the literature for efficient methodologies that sought the synthesis of 4amino-2-(trifluoromethyl)-1H-pyrroles identified only the following two methods: i) the use of 5-azido/bromo-4-methoxy/amino-1,1,1-trifluoropent-3-en-2-one through reduction of the azido group with triphenyl/trimethylphosphine, 29 and ii) allylic nucleophilic substitution of bromine with primary amines (see Scheme 1). 30 Despite the reaction occurring quite well with arylamines, and providing the expected 1H-pyrroles (Scheme 1b), when enone 1 is reacted with alkylamines, a mixture of the expected pyrrole 3 is obtained along with the new pyrrole derivative 4 (see Scheme 1c).…”

Synthesis of Methylene-Bridged Trifluoromethyl Azoles Using 5-(1,2,3-Triazol-1-yl)enones

“…[15][16][17] When targeting the selective synthesis of pyrazoles using unsymmetrical precursors, special strategies are used to assure the selec-tive synthesis. 18 In the case of triazoles, the copper(I) catalyzed Huisgen-type alkyne-azide cycloaddition (CuAAC) reaction is a well-established protocol for preparing 4-substituted 1,2,3-triazole derivatives exclusively. [19][20][21] For the synthesis of 3(5)-trifluoromethyl pyrazoles, however, several methods have been proposed, such as the application of special starting materials, [22][23][24][25] protecting groups, 26 catalysts and solvent systems.…”