Co(III)-Catalyzed Coupling of Enaminones with Oxadiazolones for Imidazole Synthesis.

Appendage speciation-oriented synthesis, as opposed to the conventional wisdom of skeleton speciation-oriented synthesis, is reported herein, emphasizing the maximization of type-, position-, and configuration-variance of appendages. A Co(III) catalytic protocol in accordance with this synthetic modality has been established for the coupling of enaminones and oxadiazolones to imidazoles, allowing the achievement of full position-variance of appendages. This translates to an expanded reaction and structural development scope and can provide fertile ground for productive organic synthesis.

Rh(III)-Catalyzed N-Amino-Directed C-H Coupling with 3-Methyleneoxetan-2-ones for 1,2-Dihydroquinoline-3-carboxylic Acid Synthesis.

Dynamic polarity analysis is proposed herein as a general tool for investigating static polarity and transient polarity and revealing expanded reactivity patterns. Through this analysis formalism, polarity matching has been established for Rh(III)-catalyzed N-amino-directed C-H coupling with 3-methyleneoxetan-2-ones, providing efficient access to 1,2-dihydroquinoline-3-carboxylic acids. The identified reaction, by virtue of the internal oxidative mechanism, showcases mild reaction conditions (room temperature), a short reaction time (2 h), and a generally high product yield.

Palladium-catalyzed coupling of amides and cyclopropanols for the synthesis of γ-diketones.

A palladium catalytic method has been developed for the coupling of amides and cyclopropanols to γ-diketones, through simultaneous C-N and C-C activation. Heteroatom ligand exchange and heteroatom-to-carbon ligation mode switching enable the achievement of molecular cross-coupling in an amide N-atom structural context-dependent manner, avoiding any stoichiometric organometallic reagent or base.

Catalytic Olefin-Imine Metathesis: Cobalt-Enabled Amidine Olefination with Enaminones.

Organic metathesis reactions allow for expedient assembly of diverse molecular skeletons and appendages through the exchange of molecular fragments. The olefin-imine variant of this process, in particular, can expand the synthetic toolbox for manipulating carbon-carbon and carbon-nitrogen bonds but has thus far been achieved only on a stoichiometric metal-mediated basis. Herein, we report the development of a catalytic olefin-imine metathesis reaction, featuring cobalt-catalyzed amidine olefination with enaminones and a versatile product synthon enabling further structural diversification.

Synthesis of quinazolinones via Cp*Co(III)-catalyzed C-H functionalization of primary amides with oxadiazolones.

Multi-heteroatom heterocycle synthesis through direct C-H bond activation is methodologically appealing but synthetically challenging. An efficient double C-N bond formation sequence to prepare quinazolinones utilizing primary amides and oxadiazolones in a catalytic redox-neutral [CoCp*(CO)I2]/AgSbF6 system, where oxadiazolone could function as an internal oxidant to maintain the catalytic cycle, is reported. Amide-directed C-H bond activation and oxadiazolone decarboxylation are key to the success of this traceless, atom- and step-economic, and cascade approach for the construction of the quinazolinone skeleton.

Cobalt Homeostatic Catalysis for Coupling of Enaminones and Oxadiazolones to Quinazolinones.

Transition metal catalysis has revolutionized modern synthetic chemistry for its diverse modes of coordination reactivity. However, this versatility in reactivity is also the predominant cause of catalyst deactivation, a persisting issue that can significantly compromise its synthetic value. Homeostatic catalysis, a catalytic process that can sustain its productive catalytic cycle even when chemically disturbed, is proposed herein as an effective tactic to address the challenge. In particular, a cobalt homeostatic catalysis process has been developed for the water-tolerant coupling of enaminones and oxadiazolones to quinazolinones. Dynamic covalent bonding serves as a mechanistic handle for the preferred buffering of water onto enaminone and reverse exchange by a released secondary amine, thus securing reversible entry into cobalt's dormant and active states for productive catalysis. Through this homeostatic catalysis mode, a broad structural scope has been achieved for quinazolinones, enabling further elaboration into distinct pharmaceutically active agents.

Rh(III)-Catalyzed Enaminone-Directed C-H Coupling with Diazodicarbonyls for Skeleton-Divergent Synthesis of Isocoumarins and Naphthalenes.

Diversity-oriented synthesis is tremendously useful for expanding the explorable chemical space but restricted by the limited available toolbox of skeleton-diversification chemistry. We report herein Rh(III)-catalyzed coupling of enaminones and diazodicarbonyls for skeleton-divergent synthesis of isocoumarins and naphthalenes. The diazodicarbonyl ring size and pH dependence of the skeleton-forming process demonstrates the achievement of both substrate- and reagent-controlled skeletal diversity generation in a single type of system. An intriguing C-C bond cleavage reactivity is critical for enabling facile synthetic access to isocoumarins.

Ruthenium-catalyzed room-temperature coupling of α-keto sulfoxonium ylides and cyclopropanols for δ-diketone synthesis.

Previous transition metal-catalyzed synthesis processes of δ-diketones are plagued by the high cost of the rhodium catalyst and harsh reaction conditions. Herein a low-cost, room temperature ruthenium catalytic method is developed based on the coupling of α-keto sulfoxonium ylides with cyclopropanols. The mild protocol features a broad substrate scope (47 examples) and a high product yield (up to 99%). Mechanistic studies argue against a radical pathway and support a cyclopropanol ring opening, sulfoxonium ylide-derived carbenoid formation, migratory insertion C-C bond formation pathway.

Cobalt-Catalyzed, Directed Intermolecular C-H Bond Functionalization for Multiheteroatom Heterocycle Synthesis: The Case of Benzotriazine.

Transition-metal-catalyzed, directed intermolecular C-H bond functionalization is synthetically useful but heavily underexplored in multiheteroatom heterocycle synthesis. Herein we report a cobalt catalytic method for the formation of a three-nitrogen-bearing benzotriazine scaffold via the coupling of arylhydrazine and oxadiazolone. This synthetic protocol features a low-cost base metal catalyst, a maximum number of heteroatoms built into a heterocycle, a distinct synthetic logic for benzotriazines, a superior step economy, and a broad substrate scope.

Regioselective C-H Amidation of (Alkyl)arenes by Iron(II) Catalysis.

A nondirected amidation reaction of aromatic C-H bond was developed under iron(II) catalysis, using sulfonyl azides as the nitrogen source. The reaction displayed a broad substrate scope and good regioselectivities in the aspects of aromatic ring vs alkyl chain and different aromatic position of (alkyl)arenes. This method provided a new protocol for the synthesis of some aromatic amines, which were hard to achieve in a previous report.

Regioselective Formal [4 + 2] Cycloadditions of Enaminones with Diazocarbonyls through RhIII-Catalyzed C-H Bond Functionalization.

A regioselective formal [4 + 2] cycloaddition for the assembly of highly functionalized benzene rings was successfully developed. In this reaction, olefinic C-H bond functionalization/cyclization cascade reaction followed by rearomatization led to the desired molecules in one step under mild reaction conditions. This protocol also displays a broad substrate scope and good tolerance to a wide range of functional groups. Additionally, the potential utility for the synthesis of highly conjugated polybenzenes and diversification of natural products was also demonstrated.