Nitrile stabilized synthesis of pyrrolidine and piperidine derivatives via tandem alkynyl aza-Prins-Ritter reactions.

An efficient methodology for the synthesis of N-(pyrrolidine-3-ylidenemethyl)acetamides mediated by triflic acid in good yields with separable Z/E isomers within a short reaction time has been demonstrated. The reaction involves the initial formation of the pyrrolidin-3-ylidenemethylium carbocation via the Prins cyclization reaction followed by the Ritter reaction to produce N-(pyrrolidine-3-ylidenemethyl)acetamides. This methodology is also used for the synthesis of their piperidine derivatives.

Leveraging cascade alkynyl Prins cyclization towards the stereoselective synthesis of spiro-furan quinazolinone scaffolds.

A TfOH-promoted, metal-free protocol has been unveiled for the synthesis of spiro-furan quinazolinones employing alkynol urea derivatives utilizing alkynyl Prins cyclization reaction. This methodology produces highly functionalized spiro-heterocycles in excellent yields with exclusive E-selectivity under ambient conditions. Furthermore, late-stage modifications incorporate bromide and acetyl functionalities into the synthesized spiro-heterocycles.

Regio- and Chemoselective Synthesis of 3-(Dihydrofuran-3(2H)-ylidene)isobenzofuran-1(3H)-imines via Tandem Alkynyl Prins- and Intramolecular Oxycyclization Reactions.

A metal-free Lewis acid-initiated protocol for the synthesis of highly substituted 3-(dihydrofuran-3(2H)-ylidene)isobenzofuran-1(3H)-imines from 2-(4-hydroxybut-1-yn-1-yl)benzamides and aldehydes has been demonstrated. The reaction involves the initial formation of dihydrofuranylidene carbocation via a Prins cyclization reaction using BF3·OEt2, followed by intramolecular cyclization to produce 3-(dihydrofuran-3(2H)-ylidene)isobenzofuran-1(3H)-imines up to E/Z = 6:1 with moderate to good yields. The methodology can also be used for the synthesis of 3-(dihydro-2H-pyran-3(4H)-ylidene)-isobenzofuran-1(3H)-imines. The strategy leads to the formation of two C-O bonds and one C-C bond with two different heterocycles connected by a tetra-substituted double bond. Post synthetic application of the reaction was extended for the synthesis of furanylidene isobenzofuranones in excellent yields.

Diastereoselective Synthesis of 2,6-Disubstituted Tetrahydropyranones via Prins Cyclization of 3-Bromobut-3-en-1-ols and Aldehydes.

Tetrahydropyranones are synthesized from 3-bromobut-3-en-1-ols and aldehydes in good yields with excellent diastereoselectivity at -35 °C. The reaction involves an initial formation of a most stable six-membered chairlike tetrahydropyranyl carbocation followed by nucleophilic attack of the hydroxyl group and subsequent elimination of HBr to give tetrahydropyranone. The carbonyl moiety of the tetrahydropyranone is converted to enol ether and esters using Wittig reaction. It is also transformed into 4-hydroxy-2,6-disubstituted tetrahydropyran with 2,4- and 4,6-cis configuration by lithium aluminum hydride in up to 96% diastereoselectivity. Furthermore, the methodology is extended toward the synthesis of novel anticancer aminoguanidine compounds.

Synthesis of Spiro[furan-2,1'-isoindolin]-3'-ones from 2-(4-Hydroxybut-1-yn-1-yl)benzonitriles and Aryl Aldehydes under the Action of Triflic Acid.

The synthesis of spiro[furan-2,1'-isoindolin]-3'-ones from 2-(4-hydroxybut-1-yn-1-yl)benzonitriles and aryl aldehydes is demonstrated. It involves the initial formation of dihydrofuranylideneisoindolinone via intramolecular sequential Prins and Ritter reactions, followed by the ring opening of the furanyl moiety to generate N-acyliminium ions and alcohols for the final cyclization reaction, and the spiro-cyclic compounds are produced in moderate to good yields. It is a one-pot, three-component reaction in which one new quaternary carbon, two five-membered rings, one C-N bond, two C-O bonds, and one C-C bond are formed. The reaction is carried out with a Brønsted acid from 0 °C to room temperature within a short period of time.

Synthesis of Thiazole-2(3H)-ones via [3,3]-Sigmatropic Rearrangement/5-exo-dig Cyclization of N-Propargylamines.

An efficient methodology has been developed for the synthesis of both di- and trisubstituted thiazol-2(3H)-ones from N-propargylamines and silver(I) trifluoromethanethiolate (AgSCF3) in good yields. The reaction proceeds via [3,3]-sigmatropic rearrangement/5-exo-dig cyclization of N-propargylamines. The starting material can be easily prepared from the A3-coupling reaction of amines, aldehydes, and alkynes. The methodology can be extended for the synthesis of thiozole-2(3H)-thione derivatives, and photophysical properties have been studied for some synthesized compounds.

In(OTf)3-Catalyzed One-Pot Tandem Mannich and Conia-Ene Cyclization Reaction of N-Propargyl Amido Alcohols with 1,3-Dicarbonyl Compounds: An Approach To Construct Tetrahydro-1H-pyrrolo[2,1-a]isoindolone-1,1-dicarboxylate and Its Application.

A one-pot tandem reaction has been developed for the synthesis of substituted tetrahydropyrroloisoindolone via Mannich reaction of N-propargyl amido alcohols with 1,3-dicarbonyl compounds followed by Conia-ene cyclization reaction in moderate to good yields catalyzed by indium(III)triflate [In(OTf)3]. The reaction is highly regioselective with an exo-cyclic double bond in the pyrrolidine ring. The substituted tetrahydropyrroloisoindolone can be converted to 5H-pyrrolo[2,1-a]isoindol-5-one via decarboxylative aromatization reaction.

Stereoselective synthesis of hexahydrofuro[3,4-b]furan-4-ol and its dimer via tandem Prins and pinacol rearrangement.

A novel synthetic route for the cyclization of ((4S,5R)-2,2-dimethyl-5-vinyl-1,3-dioxolan-4-yl)methanol with aldehydes to give hexahydrofuro[3,4-b]furan-4-ol and its dimer was developed. A variety of substituted furanol (up to 86%) and its bis-derivatives were obtained in good yields (up to 66%) with excellent diastereo- and enantio-selectivity mediated by borontrifluoride etherate. The dimer was conveniently converted into its corresponding monomer using aqueous zinc(ii) chloride in THF in quantitative yields.