The first enantioselective total synthesis of the epipolythiodiketopiperazine (ETP) natural product (-)-acetylapoaranotin (3) is reported. The concise synthesis was enabled by an eight-step synthesis of a key cyclohexadienol-containing amino ester building block. The absolute stereochemistry of both amino ester building blocks used in the synthesis is set through catalytic asymmetric (1,3)-dipo...

The first N-heterocyclic carbene (NHC)-catalyzed [3+4] cycloaddition of azomethine imines and enals is disclosed. Oxidative catalytic remote activation of enals affords 1,4-dipolarophile intermediates that react with 1,3-dipolar azomethine imines to generate dinitrogen-fused seven-membered heterocyclic products with high optical purities. Our approach also provides effective kinetic resolution ...

1,3-Dipolar cycloaddition of the anion of diethyl 1-diazomethylphosphonate, generated in situ from diethyl 1-diazo-2-oxopropylphosphonate (Bestmann-Ohira reagent), with conjugated nitroalkenes provides regioisomerically pure phosphonylpyrazoles in moderate to good yield. These pyrazoles are formed in one pot via spontaneous elimination of the nitro group. However, nitropyrazoles could be synthe...

Conjugated nitroalkenes and nitrodienes undergo smooth α-hydrazination with azodicarboxylates through an imidazole catalyzed carbon-heteroatom bond formation under Morita-Baylis-Hillman conditions. The resulting hydrazinonitroalkenes take part in 1,3-dipolar cycloaddition with azide under mild conditions to give hydrazinotriazoles. A [3 + 2] annulation with phenols and naphthols involving Micha...

A new series of pyrrolo[3',4':3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and pyrrolo[1,2-a]phenanthrolines were efficiently built up from an 8-hydroxyquinoline derivative or phenanthroline via 1,3-dipolar cycloaddition reaction involving non-stabilized azomethine ylides, generated in situ from the parent furo[3,2-h]quinoliniums/phenanthroliums, in presence of a copper(II) chloride-phenant...

An efficient, general and practical synthesis of diverse 3,4-dihydropyrazines, 6,7-dihydro-[1,2,3]triazolopyrazines and 7,8-dihydro-[1,2,3]triazolodiazepines through intramolecular 1,3-dipolar cycloaddition from amino acid derived common intermediates with high yields is described. Moreover, one-pot access to optically active 3-aryl substituted 6,7-dihydro-[1,2,3]triazolo[1,5-a]pyrazines in the...

1,3-dipolar Cycloaddition (DC) reactions have emerged as one of the important type of cycloaddition reactions from the view point of chemical and biological industry. Particularly the Azide-Alkyne Cycloaddition, also known as “Click Chemistry” has opened up new challenges in front of medicinal and pharmaceutical chemists. Bioconjugation is a technique of coupling two different biomolecules by c...

An effective and highly regio- and diastereoselective one-pot method for the synthesis of new polynuclear dispiroheterocyclic systems with five stereogenic centers (dispiro[imidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine-6,3'-pyrrolidine-2',3''-indoles]) comprising pyrrolidinyloxindole and imidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine moieties has been developed. The method relies on a 1,3-dipolar ...

We report the first study of substrate-controlled diastereoselection in a double [3 + 2] dipolar cycloaddition of benzyl azide with α,β-unsaturated imides. Using a strong Brønsted acid (triflic acid) to activate the electron deficient imide π-bond, high diastereoselection was observed provided that a 1,1,3,3-tetraisopropoxydisiloxanylidene group (TIPDS) is used to restrict the conformation of t...

Simple synthesis and biological activities of modafinil derivatives are described. The key reactions include condensation of acid and propargyl alcohol, subsequent 1,3-dipolar cycloaddition reaction of alkynes and (3-azido-propyl)cyclohexane or (4-azido-butyl)benzene in the presence of sodium ascorbate and CuSO₄·5H₂O in excellent yield. They were then evaluated for the suppression of LPS-induce...