Polysubstituted Tetrahydroquinolines Research Articles

2,2'-Bipyridine-Enabled Photocatalytic Radical [4+2] Cyclization of N-Aryl-α-amino Acids for Synthesizing Polysubstituted Tetrahydroquinolines.

A facile photocatalytic radical [4+2] cyclization of N-aryl-α-amino acids with various alkenes to access structurally polysubstituted tetrahydroquinolines has been developed. Using a simple bipyridine as a catalyst, different N-aryl-α-amino acids could be utilized as the radical precursors to react with diverse electrophilic alkenes, including exocyclic terminal alkenes, acyclic terminal alkenes, and cycloalkenes, producing 10 types of nitrogen-containing heterocyclic compounds fused in multiple frameworks in generally moderate yields with good diastereoselectivities. Scale-up synthesis and transformations of the products further demonstrated the synthetic application of this protocol. Moreover, a decarboxylative radial pathway via a proton-coupled electron transfer process for illustration of this [4+2] cyclization was proposed on the basis of the control experiments. This process is highlighted by a simple bipyridine photocatalysis, mild reaction conditions, various N-aryl-α-amino acids and alkene materials, and application for the modification of natural products.

Kinetics and mechanism of antioxidant action of polysubstituted tetrahydroquinolines in liquid‐phase oxidation reactions of organic compounds by oxygen

AbstractThe antioxidant properties of a series of biologically active polysubstituted tetrahydroquinolines containing chromanyl fragments have been experimentally studied in the liquid phase. Probed was the ability of the substrates to kinetically retard the initiator‐induced radical chain oxidation by O2 of the model compounds 1,4‐dioxane or isopropyl alcohol. The oxidation reactions were monitored at 348 K using a manometric technique, measuring under various initial conditions the time‐dependent concentration of oxygen in the gas phase above a reaction mixture containing the radical‐chain initiator azobisisobutylnitrile and the substrates under study. When tetrahydroquinolines were present, the kinetic curves of oxygen absorption exhibited characteristic induction periods (τ) wherein the reaction rate is immeasurably small. The dependence of τ on the initial concentration of the introduced antioxidants has been determined and the results interpreted within the framework of a classical scheme describing the radical‐chain oxidation of organic compounds in the presence of an inhibitor. Values of the stoichiometric coefficient of inhibition, f, which is related to the number of chain propagating radicals destroyed by each antioxidant molecule, is >>2 for all the studied antioxidants. Consistent with the existing literature, it is inferred that the original antioxidant molecule is regenerated from its radical inhibition product during reaction. Previous studies suggest that oxyperoxy radicals play an important role in the inhibitor regeneration process due to their ability to act either as an oxidizer (in chain propagation) or as a reducing agent (in regeneration of the inhibitor from its corresponding radical). In the presently studied systems containing 1,4‐dioxane, it is argued that the source of oxyperoxy radicals is 2‐hydroxy‐1,4‐dioxane. A reaction mechanism that includes the stages of inhibitor regeneration and that is quantitatively consistent with the present results has been developed. It is suggested that the high antioxidant capacity of the tetrahydroquinoline derivatives is due to their large chain breaking rate constants in conjunction with regeneration of the inhibitor during chain termination processes. The relationship of the studied chemical structures and their antioxidant capacity is discussed.

Reagent-free synthesis of 2,3,4-polysubstituted tetrahydroquinolines: application to the formal synthesis of (±)-martinellic acid and martinelline

The simple and one-pot method for the synthesis of polysubstituted tetrahydroquinolines from readily available anilines and aldehydes under reagent-free conditions has been developed. The scope of the transformation has been demonstrated. This method has been successfully applied to the rapid formal synthesis of (±)-martinellic acid and martinelline.

ChemInform Abstract: Highly Regioselective Synthesis of Polysubstituted Tetrahydroquinolines by an Iodine‐Induced Tandem Cyclization Reaction from Propargylic Alcohols and Amines.

AbstractA versatile, convenient, and environmentally friendly protocol for the synthesis of substituted tetrahydroquinolines is presented (21 examples).

Highly Regioselective Synthesis of Polysubstituted Tetrahydroquinolines by an Iodine‐Induced Tandem Cyclization Reaction from Propargylic Alcohols and Amines

A versatile, convenient, and environmentally friendly protocol for the synthesis of substituted tetrahydroquinolines is presented (21 examples).

ChemInform Abstract: FeCl3‐Mediated Synthesis of Polysubstituted Tetrahydroquinolines via Domino Mannich/Friedel—Crafts Reactions of Aldehydes and Amines.

AbstractDomino Mannich—intramolecular Friedel—Crafts alkylation—intermolecular Friedel—Crafts alkylation reaction of aliphatic aldehydes with aromatic amines is smoothly catalyzed by FeCl3 to give polysubstituted tetrahydroquinolines in moderate yields and moderate to good diastereoselectivities.

ChemInform Abstract: Highly Enantioselective Synthesis of Polysubstituted Tetrahydroquinolines via Organocatalytic Michael/Aza‐Henry Tandem Reactions.

AbstractThe reaction proceeds with the highest diastereoselectivity for ortho‐substituted aromatic imine substrates [cf.

Highly Enantioselective Synthesis of Polysubstituted Tetrahydroquinolines via Organocatalytic Michael/Aza-Henry Tandem Reactions

Highly enantioselective chiral bifunctional thiourea catalyzed asymmetric tandem reactions for synthesis of substituted tetrahydroquinolines are described. Substituted tetrahydroquinolines were given in good yields (up to 98%), high enantioselectivities (up to >99% ee), and diastereoselectivities (up to 20:1 dr).

FeCl3-Mediated synthesis of polysubstituted tetrahydroquinolines via domino Mannich/Friedel–Crafts reactions of aldehydes and amines

A useful method to construct highly substituted tetrahydroquinolines has been developed through an iron(III) chloride-mediated domino Mannich and intramolecular Friedel-Crafts alkylation followed by intermolecular Friedel-Crafts alkylation reactions of aliphatic aldehydes with aromatic amines.

ChemInform Abstract: A Stereoselective Route to Polysubstituted Tetrahydroquinolines by Benzotriazole-Promoted Condensation of Aliphatic Aldehydes and Aromatic Amines.

By the promotion of benzotriazole (20 mol %), two molecules of anilines (or other arylamines) and two molecules of phenylacetaldehyde (or o-bromophenylacetaldehyde) condensed to give a series of 1,2,3,4-tetrahydroquinolines in a stereoselective manner. By the catalysis of SmI(2) or SmI(3), the N-(alpha-aminoalkyl)benzotriazoles derived from anilines and (R)-glyceraldehyde acetonide dissociated to the corresponding iminium and enamine species, which underwent asymmetric [4 + 2] cycloadditions to give optically active tetrahydroquinolines.

A stereoselective route to polysubstituted tetrahydroquinolines by benzotriazole-promoted condensation of aliphatic aldehydes and aromatic amines

By the promotion of benzotriazole (20 mol %), two molecules of anilines (or other arylamines) and two molecules of phenylacetaldehyde (or o-bromophenylacetaldehyde) condensed to give a series of 1,2,3,4-tetrahydroquinolines in a stereoselective manner. By the catalysis of SmI(2) or SmI(3), the N-(alpha-aminoalkyl)benzotriazoles derived from anilines and (R)-glyceraldehyde acetonide dissociated to the corresponding iminium and enamine species, which underwent asymmetric [4 + 2] cycloadditions to give optically active tetrahydroquinolines.

ChemInform Abstract: Parallel Synthesis of Polysubstituted Tetrahydroquinolines.

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Solid support synthesis of polysubstituted tetrahydroquinolines via three-component condensation catalyzed by Yb(OTf) 3

Solid support synthesis of polysubstituted tetrahydroquinolines is described. The procedure is based on a three-component condensation involving immobilized derivatives of 4-aminophenylalanine, aldehydes, alkenes and Yb(OTf) 3 as a catalyst. The methodology is further expanded to the solid support synthesis of tricyclic tetrahydroquinoline by the concomitant formation of the Schiff base followed by intramolecular trap of the alkene.

Parallel synthesis of polysubstituted tetrahydroquinolines

A three-component cycloaddition was used to prepare a library of polysubtituted tetrahydroquinolines. Reaction conditions were optimised and a large range of anilines, aldehydes and alkenes were tested.