A Cycloaddition Approach toward the Synthesis of Substituted Indolines and Tetrahydroquinolines

Abstract

The intramolecular Diels-Alder reaction of 2-substituted aminofurans (IMDAF) results in the formation of various indolines and tetrahydroquinolines. The isolation of these ring systems from the IMDAF reaction can be rationalized in terms of an initial [4 + 2]-cycloaddition that first produces an oxa-bridged cycloadduct, which was not detected since it readily underwent nitrogen-assisted ring opening. Proton exchange followed by an eventual dehydration provides the aromatic product. In certain cases, the intermediate cyclohexadienol can be isolated and independently converted to the final product in high yield. The starting 2-aminofurans were readily prepared from furanyl acyl azide by a Curtius rearrangement in the presence of an alcohol. Alkylation of the resulting N-alkyl carbamate with an alkenyl bromide allows for the synthesis of a wide variety of cycloaddition precursors. The scope of the IMDAF reaction was evaluated by using mono- and disubstituted alkenes, electron rich and electron deficient olefins, and acetylenic tethers. Cyclic 2-amidofurans were also synthesized using a related intramolecular Diels-Alder reaction of 2-amido-substituted oxazoles which contain a tethered alkyne. This transformation represents a new route to this rare heterocyclic ring system. The sequential cycloaddition method was used for a formal synthesis of the pyrrolophenanthridone alkaloid hippadine.

Heterocyclization of amides of alkenylcarboxylic acids

“…Подібного роду перетворення реалізовано на прикладі N-фураніламідів 160, які в розчині то-луолу при високій температурі циклізуються до дигідрохінолінонів 161 [83][84][85] (схема 66).…”

Synthesis, Crystal and Molecular Structure Studies and DFT Calculations of Phenyl Quinoline-2-Carboxylate and 2-Methoxyphenyl Quinoline-2-Carboxylate; Two New Quinoline-2 Carboxylic Derivatives

“…Quinoline derivatives represent a major class of heterocycles and are found in natural products [1,2], numerous commercial products, including fragrances, dyes [3] and biologically active compounds [4,5]. Quinoline alkaloids such as quinine, chloroquin, mefloquine and amodiaquine are used as efficient drugs for the treatment of malaria [6].…”

Bleaching earth clay (pH 12.5)/PEG-400: an efficient recyclable catalytic system for synthesis of 5,6,7,8-tetrahydroquinoline-3-carbonitrile derivatives

“…The tetrahydroquinoline framework is considered to be one of the privileged structures in the area of drug discovery, as compounds containing this scaffold display a wide range of biological and pharmaceutical activities [4][5][6][7][8][9][10][11][12], including anti-human immunodeficiency virus (HIV) [13,14], anticancer [15,16], and antimalarial action [17], cholesteryl ester transfer protein inhibition [18], antidiabetic [19] and antifungal activity [20], C 5a receptor antagonism [21], RET tyrosine kinase inhibition [22], etc.…”