Purines and deazapurines constitute an important class of natural products and drugs. The cyclization of heterocyclic enamines with electrophiles allows for the synthesis of a variety of drug-like compounds and natural product analogues, such as novel fluorine-substituted purines and deazapurines.

Abstract: Cyclization reactions of heterocyclic enamines with 1,3-dielectrophiles, such as 1,3-diketones, enaminones or 3-chloro-2-en-1-ones, provide access to a variety of pharmacologically relevant fluorinated purine analogues. Purines were prepared also by inverse electron-demand Diels-Alder reactions of heterocyclic enamines with triazines. Amidino-C-glycosides in their reactions with 1,3-dielectrophiles afforded pyrimidine-C-glycosides.

Review: Synlett 2022, 33, 440-457.

Period of investigation: 2009 - Today

Keywords: heterocyclic enamines; cyclizations; heterocycles

Abstract: Domino reactions of heterocyclic enamines with chromone derivatives provide a convenient access to a great variety of annulated heterocyclic ring systems. The course of the reaction depends on the type of substituent located at position 3 of the chromone.

Review: Synlett 2022, 33, 207–223.

Period of investigation: 2009 - Today

Keywords: heterocyclic enamines; cyclizations; heterocycles; chromones

Abstract: Cyclization reactions of nitro-substituted electrophilic building blocks with various nucleophiles allow for the synthesis of various nitro-substituted carbo- and heterocycles. The electron-withdrawing nitro group can be easily transformed to an electron-donating amino group which is not only pharmacologically relevant, but can also act as a nucleophile in inter- and intramolecular reactions with electrophiles, such as aldehydes, and can also be converted to other functional groups. The nitro group has the capacity to activate compounds for regioselective palladium catalyzed CH-arylation reactions. Inter- and intramolecular CH-arylations of nitro-substituted heterocyclic building blocks, such as 4-nitropyrazoles, 4-nitroimidazoles, 2-nitroindole and nitro-substituted purine analogues, allow for a convenient diversity-oriented approach to the corresponding arylated products. In addition, the nitro group can act as a leaving group in S_NAr reactions.

Review: Synlett 2024, DOI: 10.1055/s-00000083.

Period of investigation: 2007 - 2019

Keywords: nitro compounds; cyclizations; heterocycles; silyl enol ethers; heterocyclic enamines

Abstract: A variety of domino and multicomponent reactions were developed which include domino Knoevenagel / hetero-Diels-Alder reactions, the combination of Knoevenagel reactions with [3+2] cycloadditions of nitrogen ylides, domino Knoevenagel / enamine cyclization reactions, formal [3+3] cyclizations of pyridinium salts, [3+3] cyclizations of thioxindoles with fluoroaroyl chlorides, cyclizations of heterocyclic enamines with diimines and triazines, domino [4+2] / retro [4+2] reactions, formal [3+3] cyclizations of 2-ethynylpyridines with enones, reaction of trifluoromethyl-substituted 1,3-diketones with lithiated alkynes and formal [3+2] cyclizations of 2,3-dihalopyridines with imines. These reactions provide a convenient access to various drug-like compounds.

Review: Peter Langer, Eur. J. Org. Chem. 2024, https://doi.org/10.1002/ejoc.202400153.

Period of investigation: 2009 - Today

Keywords: domino reactions; cyclizations; iminium salts