Synthesis of Benzodioxepinones and Benzoxazepinones via Tandem Oxidation and Iodolactonization of 2-O/N-tethered Alkenyl Benzaldehyde Mediated by CuI/TBHP.

An efficient methodology for the synthesis of halogenated benzodioxepinones and benzoxazecinones has been developed via tandem oxidation and iodolactonization reaction of 2-O/N-tethered alkenyl benzaldehydes mediated by CuI and tertiarybutylhydro-peroxide in acetonitrile at 70 °C in moderate to good yields. The reaction involves initial oxidation of aldehyde to acid followed by iodolactonization. Terminal propargyl ether resulted in a mixture of mono- and diiodido-3-methylene-1,4-dioxepin-5-ones. The post-synthetic modification of the reaction products leads to the formation of corresponding thiocyanate, azide, thioether, and triazole derivatives.

Stereoselective synthesis of gem-dihalopiperidines via the halo-aza-Prins cyclization reaction: access to piperidin-4-ones and pyridines.

An efficient methodology for the synthesis of 4,4-dihalopiperidine derivatives in excellent yields has been developed using N-(3-halobut-3-en-1-yl)-4-methylbenzenesulfonamide and an aldehyde catalyzed by In(OTf)3. The reaction involves an initial formation of a six-membered carbocation via the aza-Prins cyclization reaction followed by a nucleophilic attack by a halide ion to give 4,4-dihalopiperidine. The dihalopiperidine is converted to tetrahydropiperidinone using Ac2O/Et3N in DCM/H2O (1 : 1). It is also utilized for the synthesis of pyridine scaffolds by treatment with DBU. Furthermore, the dihalopiperidine is transformed to its enol ether derivatives using KOH in alcohol.

Synthesis of tetrahydroquinazolines from 2-aminobenzonitriles and alkylidene malonates via 1,4-conjugate addition and an unprecedented rearrangement reaction.

An efficient methodology for the synthesis of highly diverse tetrahydroquinazoline scaffolds from 2-aminobenzonitriles and alkylidene malonates via 1,4-conjugate addition followed by an unprecedented rearrangement has been demonstrated. The methodology is further applicable for the synthesis of quinazolines and tetracyclic compounds. Some of the synthesized compounds exhibit photophysical properties.

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.

Base-Promoted [4 + 2] Annulation Reaction of In Situ-Generated Azadienes from N-Propargylamines with Active Methylene Compounds: Access to Highly Functionalized 2-Pyridones.

A facile and efficient synthesis of structurally diversified 2-pyridones is demonstrated using the [4 + 2] annulation of in situ generated azadienes from N-propargylamines and active methylene compounds. The reaction is promoted by an inorganic base giving moderate to good yields. The developed methodology is applicable for the direct and formal synthesis of various bioactive molecules. The synthetic utility of the protocol was also illustrated by late-stage functionalization of the products.

Synthesis of 1,2,3-triazole-fused N-heterocycles from N-alkynyl hydroxyisoindolinones and sodium azide via the Huisgen reaction.

An efficient methodology for the synthesis of dihydro[1,2,3]triazolo-pyrimidoisoindolones and dihydro[1,2,3]triazolo-diazepinoisoindolones has been developed using the Huisgen reaction from sodium azide and alkyne substituted amido alcohols in moderate to good yields. The reaction involves the in situ generation of the N-acyliminium ion intermediate, which undergoes a nucleophilic attack by the azide ion, followed by a [3 + 2]-intramolecular azide-alkyne cycloaddition reaction. Importantly, the reaction proceeds without the involvement of any transition metal catalyst. This methodology can be further utilized for the synthesis of dihydro[1,2,3]triazolo-pyrimidoisoindolthiones via thionation of amides.

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.

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.

K2S2O8-Mediated Synthesis of Highly Functionalized Pyrroles via Oxidative Self-Dimerization of N-Propargylamines.

An efficient methodology has been developed for the synthesis of tetra- and pentasubstituted pyrroles via oxidative self-dimerization of N-propargylamines catalyzed by silver benzoate in the presence of K2S2O8 in good yields. The protocol provides a simple route for the synthesis of both tetra- and pentasubstituted pyrroles with two carbonyl groups in the side chain. The methodology can be extended toward the synthesis of pyrrolo[3,4-d]pyridazine.