An Organocatalytic Cascade Spirocycloaddition Reaction for the Construction of Spiro [indoline-3,3-piperidin]

Abstract We report a simple protocol for the synthesis of heterocyclic indoloquinoxalines and 2-naphthylquinazolinones by an oxidative aromatization from aromatic aldehydes or benzyl alcohols. For aromatic aldehydes, a diphenyl hydrogen phosphate/Cu(OTf)2/t-BuOOH system delivered the products in high yields (73–93%). From benzyl alcohols, a Fe(NO3)3·9H2O/(2,2,6,6-tetramethylpiperidin-1-yl)oxyl/air system was effective, and the products were obtained in moderate to high yields (51–75%). The indolo[1,2-a]quinoxaline compounds displayed fluorescence emission bands at 501–533 nm. Moreover, intramolecular hydrogen bonding was vital for the free rotation of the aryl–aryl bond in ortho-hydroxyindolo[1,2-a]quinoxalines.

Abstract Tropomyosin receptor kinase (TRK) inhibitors have emerged as promising therapeutic agents for various cancers. In this study, we report the discovery and characterization of CH7070868, a novel and potent TRK-selective inhibitor. Through structure–activity relationship studies, we optimized the lead compound (CH7057288) to achieve superior TRK inhibition while reducing the risk of drug–drug interactions (CYP3A4 induction). CH7070868 demonstrated high selectivity for TRK over other kinases (KDR and LCK) and exhibited potent inhibitory activity in both biochemical and cellular assays. Our findings suggest that CH7070868 represents a promising candidate for further development as a next-generation TRK inhibitor with an enhanced efficacy.

Abstract A bidentate Co(III)-catalyzed α-olefination of nitriles has been developed. This one-pot protocol provides a simple procedure for the synthesis of alkenyl nitriles from diverse alcohols and nitriles. An extensive substrate scope, good functional-group compatibility, and high atom economy are displayed. Preliminary mechanistic studies revealed that C=C bond formation proceeds through activation of the O–H bond of the alcohol via an unsaturated 16-electron intermediate cobalt complex, and subsequent condensation of the in situ-formed aldehyde with the nitrile. Remarkably, this method liberates H2 and H2O as the only byproducts.

Abstract A novel tandem reaction starting from alkynones and cyclic ketones has been developed to efficiently synthesize pyranoindolones fused with a medium-sized ring. This process involves a base-induced C–C σ-bond cleavage reaction of cyclic ketone and subsequent I2-mediated 1,2-acyl migration/cyclization reaction. Transition-metal-free and easily accessible starting materials make this 1,2-acyl migration/cyclization methodology attractive.

Abstract Carbon–carbon (C–C) bond formation reactions have contributed significantly to the construction of numerous important molecules that have contributed in various dimensions. Heterogeneous catalysts that are recyclable and can convert a chemical reaction with the same affinity as that of the homogeneous counterpart provide an economically viable path. This account, therefore, focuses on different types of C–C bond formation reactions triggered by transition metal catalysts supported mostly on zeolite-Y and a few metal oxide nanocatalysts. The account comprises our recent works devoted to various C–C bond formation reactions performed by such heterogeneous catalysts including photocatalysts.1 Introduction2 Biaryl Synthesis by C–Cl Bond Activation3 Synthesis of 3,3′-Bis(indolyl)methanes4 C2 Trimerization of Indoles5 Cross-Aldol Condensation Reaction6 Friedel–Crafts Benzylation of Naphthol and Phenol7 Oxidative C–C Coupling of Naphthols8 Conclusion

Abstract This study introduces a sustainable mechanochemical approach for the nitration of electron-rich ortho and para di- and trialkoxyarenes using iron(III) nitrate nonahydrate (Fe(NO3)3·9H2O) as a source of nitro radicals. Conventional nitration methods require harsh conditions and hazardous reagents, limiting their application. Herein, mechanochemical activation offers a rapid and efficient alternative with minimal solvent and a reduced reaction time. Screening identified Fe(NO3)3 as the most effective nitrating agent, with successful application with a variety of ortho and para di- and trialkoxyarenes while maintaining high regioselectivity. The scalability and environmental benefits of the method underscore its potential in organic synthesis, advancing a practical, green protocol for radical aromatic nitration.

Abstractσ-Type cyclopropenium cations (CPCs), which are formally generated by removing one substituent on the alkene of cyclopropenes, represent promising intermediates for forging functionalized cyclopropenes. However, σ-type CPCs are challenging to access and their synthetic utility remains largely unexplored. Recently, we introduced electrophilic cyclopropenyl-gold(III) species as equivalents of σ-type CPCs, which can then react with terminal alkynes or vinylboronic acids to afford alkynyl- or alkenyl-cyclopropenes. The merging of redox gold catalysis and a new class of hypervalent iodine reagents—the cyclopropenyl benziodoxoles (CpBXs)—plays a central role in generating the σ-type CPC equivalents. With the same reagents, we have also developed a synergistic Au/Ag bimetallic catalytic cyclopropenyl cross-coupling system that enables 1,1′-bicyclopropenyl derivatives to be forged in an efficient and modular manner. Our strategy provides access to previously inaccessible, yet highly useful, functionalized cyclopropenes, thereby significantly advancing both cyclopropene and hypervalent iodine chemistry.1 Introduction2 Transferring σ-Type CPCs to Terminal Alkynes3 Transferring σ-Type CPCs to Vinylboronic Acids4 Transferring σ-Type CPCs to Terminal Cyclopropenes5 Reaction Mechanism6 Conclusions

Abstract In this account, we summarize our recent progress on the structural regulation and selective catalysis of biomass-derived carbon-based non-precious nanocatalysts (Fe, Co, Ni, and Cu) in organic reactions that include the selective hydrogenation of functional nitro compounds to amines, selective oxidation of alkenes, selective coupling reactions, and selective hydrogenation of unsaturated aldehydes.1 Introduction2 Fe-Based Catalysts3 Co-Based Catalysts4 Ni-Based Catalysts5 Cu-Based Catalysts6 Conclusions

Abstract Asymmetric electrocatalytic processes hold great promise for the sustainable synthesis of chiral compounds. However, maintaining stereochemical control during the anodic oxidative cross-dehydrogenative coupling of different nucleophiles poses significant challenges. To address this, a novel electrocatalytic strategy has been developed that achieves an enantioconvergent nitroalkylation between benzoxazolyl esters and nitroalkanes via radical pathways. This method produces enantioenriched nitro esters without the need for additional stoichiometric chemical oxidants. Mechanistic studies have revealed that the nickel catalyst plays a critical role in both the electrochemical activation and the determination of stereoselectivity. This approach facilitates transformations that are challenging under thermal conditions, including umpolung reactivity, the formation of quaternary carbon centers, and remote enantiocontrol.