Propargyl Imines Research Articles

Radical selenylative cyclization of trifluoromethyl propargyl imines for the synthesis of trifluoromethyl- and seleno-azaspiro[4,5]-tetraenones and quinolines.

A radical selenylative cyclization of trifluoromethyl propargyl imines with diselenides for the regiodivergent construction of diversely functionalized azaspiro[4,5]-tetraenones and quinolines has been developed, which enables dual incorporation of CF3 and Se groups into heterocycles in a one-pot reaction. When using Oxone as a green oxidant, the reaction proceeds through oxidative dearomative ipso-annulation or intramolecular ortho-annulation exhibiting good regioselectivity. The synthetic utility of this method is demonstrated by a scale-up reaction and further modification of the obtained products.

An N-heterocyclic carbene-catalyzed enantioselective [3 + 2] annulation of enals with propargylic imines: access to γ,γ-disubstituted pyrrolidin-2-ones bearing quaternary stereogenic centers

An N-heterocyclic carbene-catalyzed enantioselective [3 + 2] annulation of enals with propargylic imines for the construction of γ,γ-disubstituted pyrrolidin-2-ones was developed.

Concise design and synthesis of pyridine-fused heterocycles via 6π-Azaelectrocyclization process of iminoalkyne derivatives

A concise and regioselective approach to the synthesis of pyridine-fused heterocycles and benzoxazepine derivatives was developed. Propargyl imines derived from aromatic aldehydes and propargyl amine underwent 6π-electrocyclization reactions at high temperatures in high yields to form pyridine-fused heterocycles. Application of the same methodology to aromatic imines having a hydroxyl group in the ortho position resulted in the formation of (benz)oxazepine derivatives. The formation mechanism of the products was discussed.

ChemInform Abstract: Development of a syn‐Selective Mannich Reaction of Aldehydes with Propargylic Imines by Dual Catalysis: Asymmetric Synthesis of Functionalized Propargylic Amines.

AbstractEnolizable aldehydes are coupled with C‐alkynyl imines to produce an intermediate aldehyde adduct which is immediately reduced to the alcohol.

Development of a syn-Selective Mannich Reaction of Aldehydes with Propargylic Imines by Dual Catalysis: Asymmetric Synthesis of Functionalized Propargylic Amines.

Direct coupling of enolizable aldehydes with C-alkynyl imines is realized affording the corresponding propargylic Mannich adducts of syn configuration, thus complementing previous methods that gave access to the anti-isomers. The combination of proline and a urea Brønsted base cocatalyst is key for the reactions to proceed under very mild conditions (3-10 mol % catalyst loading, dichloromethane as solvent, -20 °C, 1.2 molar equivalents of aldehyde) and with virtually total stereocontrol (syn/anti ratio up to 99:1; ee up to 99 %). Some possibilities of further chemical elaboration of adducts are also briefly illustrated.

Intramolecular heterocyclization and cyclopalladation of selenoanisole substituted propargyl imines: Synthesis and reactivity of Pd–C bond towards alkynes

The intramolecular cyclization of o-SeMeC6H4CCC–(CF3)(NAr) with [PdCl2(PhCN)2] to dimeric cyclopalladated benzoselenophene has been developed under mild conditions. The reactivity of the new dimeric cyclopalladated benzoselenophene is examined towards insertion of alkynes into Pd–C bond. The reactivity study is also extended to Pd–C bond of dimeric cyclopalladated benzothiophenes towards insertion of alkynes.

Heck-type coupling of intramolecularly-generated thiopalladacycles with alkenes: One pot syntheses of 3-alkenylbenzo[b]thiophenes

A method for stoichiometric functionalization of benzothiophene is developed by Heck-type coupling of alkenes with intramolecularly-generated thiopalladacycles obtained from palladium salts and ortho-thioanisole-substituted propargyl imines. The synthetic strategy for preparing structurally diverse 3-alkenylbenzo[b]thiophene is also extended to 3-alkenylbenzo[b]selenophenes.

Combined α,α-dialkylprolinol ether/Brønsted acid promotes Mannich reactions of aldehydes with unactivated imines. An entry to anti-configured propargylic amino alcohols

The first enamine mediated anti-selective and highly enantioselective Mannich reaction of aldehydes and unactivated imines is reported. The key for success is the combined use of a Bronsted acid with an α,α-dialkylprolinol ether catalyst that leads to adducts with good yields (typically 70–75%), anti : syn ratios greater than 90 : 10, and ee values usually above 95%. The method works particularly well with propargylic imines and, unlike previous catalytic routes to optically active propargylamines, provides adducts featuring two contiguous stereocenters and a functionalized side chain amenable for ulterior synthetic applications.

New cyclopalladated benzothiophenes: a catalyst precursor for the Suzuki coupling of deactivated aryl chlorides

Dimeric benzothiophene-based palladacycles were synthesized from thioanisole-substituted perfluoroalkyl propargyl imines and palladium(II) salts via an intramolecular thiopalladation pathway. The treatment of benzothiophene-based palladacycles with an excess of phosphine ligands in benzene at room temperature selectively afforded trans-bis(phosphine) palladium complexes in good yields. The trans-bis(tricyclohexylphosphine) palladium complex was found to be an active catalyst in the Suzuki coupling of electron rich aryl chlorides. The complex was also employed in the catalytic synthesis of sterically hindered biaryls. The anticancer activity of palladacycles is also discussed.

Synthesis of highly substituted 2-perfluoroalkyl quinolines by electrophilic iodocyclization of perfluoroalkyl propargyl imines/amines

A series of highly substituted 2-perfluoroalkyl-3-iodoquinolines are prepared by two different methods in good to excellent yields under mild reaction conditions. The first method involves iodocyclization of perfluoroalkyl propargyl imines with I(2)-CAN. The second method involves iodocyclization of perfluoroalkyl propargyl amines using I(2) and ICl. The perfluoroalkyl propargyl amines are prepared in excellent yields via Sonogashira coupling of easily accessible imidoyl iodides with alkynes followed by reduction with NaBH(3)CN. The scope of this methodology is extended by using the resulting 2-perfluoroalkyl-3-iodo quinolines in Suzuki, annulation, dehalogenation and carboxylation reactions. Antimalarial activity of the 2-perfluoroalkyl-3-iodoquinolines is discussed.

A protodesilylation route for 2-Aza-1,3-diene synthesis

A new methodology for 2-aza-1,3-diene synthesis involving protodesilylation reactions of N-1-triethylsilylallyl-imines and their propargyl analogs is described. Synthetic sequences for the preparation of these allyl and propargyl imines starting with propargyl amine are presented. The silylallyl and silylpropargyl imines are transformed to 2-azadiene products by use of CsF induced desilylation via a pathway involving generation and regioselective γ-protonation of intermediate 1-imino-allyl and propargyl anions. Alkylative-desilylation of the silylallyl and propargyl imines leads to generation of N-1-alkylallyl-imines and propargyl analogs via α-alkylation of intermediate anions. Finally, the stereochemistry of azadiene formation has been probed by use of the conversion of N-(1-triethylsilylpropen-1-yl) benzaldimine to 1-phenyl-2-aza-1,3-pentadiene. Solvent, water concentration and a metal cation complexing agent all appear to influence the stereoselectivity of this process.