ABSTRACT
A rhodium(III)-catalyzed controllable [4 + 1] and [4 + 2] annulation of N-aryl pyrazolones with maleimides as C1 and C2 synthon has been explored for the synthesis of spiro[pyrazolo[1,2-a]indazole-pyrrolidines] and fused pyrazolopyrrolo cinnolines. The product selectivity was achieved through time-dependent annulation. The [4 + 1] annulation reaction involves sequential Rh(III)-catalyzed C-H alkenylation of N-aryl pyrazolone, followed by an intramolecular spirocyclization via aza-Michael-type addition to afford spiro[pyrazolo[1,2-a]indazole-pyrrolidine]. However, prolonged reaction time converts in situ formed spiro[pyrazolo[1,2-a]indazole-pyrrolidine] into fused pyrazolopyrrolocinnoline. This unique product formation switch proceeds via strain-driven ring expansion through a 1,2-shift of the C-C bond.
ABSTRACT
A Rh(III)-catalyzed cascade C-H activation and cyclization of 2-aryl benzimidazoles with maleimides for the synthesis of benzimidazole-fused isoquinolines and benzimidazole-spiro isoindoles is reported. Switchable selectivity towards the formation of these two distinct products can be achieved using unsubstituted and substituted benzimidazoles at the ortho-position of the phenyl ring. Mechanistically, C-H activation followed by migratory insertion of maleimide forms a Heck-type intermediate. Unsubstituted benzimidazole undergoes aza-Michael addition to form a (4 + 2) fused product, whereas ortho-substituted phenyl benzimidazole causes steric clash to deliver a (4 + 1) spiro-adduct favorably via acid-catalyzed intramolecular annulation.
Subject(s)
Benzimidazoles , Isoquinolines , Catalysis , CyclizationABSTRACT
Two new classes of heteroarene-fused [1,2,4]thiadiazole and [1,2,4]selenadiazole are synthesized through the iodine-mediated [3 + 2] oxidative cyclization of 2-aminoheteroarenes and isothiocyanates/isoselenocyanates. This oxidative [3 + 2] annulation strategy is highly regiospecific to proceed a selective C-N bond formation at the endo-nitrogen of 2-aminoheteroarenes followed by an intramolecular oxidative N-S/N-Se bond formation. It is the first example of an I2-mediated oxidative nitrogen-selenium (N-Se) bond formation.
ABSTRACT
BACKGROUND: Osteogenesis imperfecta (OI) is a genetic connective tissue disorder characterized by skeletal deformity and increased risk of fracture. Independent mobility is of concern for OI patients as it is associated with the quality of life. The present study investigates the variation of kinetic and kinematic gait parameters of type IV OI subjects and compares them with age-matched healthy subjects. MATERIALS AND METHODS: Gait analysis is performed on five type IV OI patients and six age-matched normal subjects. Spatiotemporal, kinematic, and kinetic data are obtained using Helen Hayes marker placement protocol. RESULTS: The results indicate an imprecise double-humped profile for vertical ground reaction force (GRF) with reduced ankle push off power and walking speed for OI subjects. Moreover, a comparison of vertical GRFs in OI subjects with that of healthy subjects suggests lower values for the former. The results encourage and motivate for further investigation with a bigger set of subjects. CONCLUSION: This information may be useful in developing a better understanding of pathological gait in type IV OI subjects, which ultimately helps the design of subject-specific implants, surgical preplanning, and rehabilitation.
ABSTRACT
A novel and efficient method for the one-pot synthesis of 2 H-indazole from readily available building blocks is reported. The reaction of 2-nitrobenzylamines with zinc and ammonium formate underwent partial reduction to nitroso-benzylamine followed by an intramolecular cyclization to afford 2 H-indazole via N-N bond formation. The carboxylic acid moiety of indazole was proceeded to regioselective alkyne insertion under ruthenium catalysis to form pyranone-fused indazoles. The regioselectivity is influenced by the weak coordination of indazole ring nitrogen to the metal center.
Subject(s)
Alkynes/chemistry , Indazoles/chemical synthesis , Pyrans/chemical synthesis , Benzylamines/chemistry , Catalysis , Cyclization , Molecular Structure , Oxidation-Reduction , Ruthenium/chemistry , Stereoisomerism , Zinc/chemistryABSTRACT
A divergent reaction of 2-aminobenzimidazole with isothiocyanates and dihalomethanes has been developed for the selective synthesis of benzoimidazothiazetidine and benzoimidazothiadiazine. A single-pot reaction of 2-aminobenzimidazole in the presence of sodium hydride delivers benzoimidazothiazetidine, whereas triethylamine promotes the formation of benzoimidazothiadiazine via a sequential stepwise fashion. The reaction sequence involves the initial formation of thiourea followed by regioselective nucleophilic addition and intramolecular ring-closing with dihalo electrophiles. The observed regioselectivity of this reaction is governed by the nature of bases and the reaction sequence.
ABSTRACT
An efficient cascade synthesis of novel benzimidazole linked alkyloxypyrrolo[1,2-a]quinoxalinones was explored on soluble polymer support under microwave irradiation. Two exclusive protocols have been developed for the partial and full reductive cyclization by controlling the microwave energy. Commencing from the same substrate, ortho nitro pyrrol carboxylates, N-hydroxy pyrroloquinoxalinones were obtained by partial reductive cyclization (60 °C, 7 min), and the synthesis of pyrroloquinoxalinones was accomplished by full reductive cyclization (85 °C, 12 min). This method represents the first synthesis of N-hydroxy pyrroloquinoxalinones using Pd/C and ammonium formate as reducing agents. Further employing a variety of alkyl bromides, the obtained pyrroloquinoxalinones were transformed to their corresponding O- and N-alkylated analogues to deliver the diversified, novel molecular entities.