Recent approaches for the synthesis of heterocycles from amidines via a metal catalyzed C-H functionalization reaction.

Transition metal catalyzed C-H bond activation has become one of the most important tools for constructing new chemical bonds. Introducing directing groups to the substrates is the key to a successful reaction, these directing groups can also be further transformed in the reaction. Amidines with their unique structure and reactivity are ideal substrates for transition metal-catalyzed C-H transformations. This review describes the major advances and mechanistic investigations of the C-H activation/annulation tandem reactions of amidines until early 2024, focusing on metal-catalyzed C-H activation of amidines with unsaturated compounds, such as alkynes, ketone, vinylene carbonate, cyclopropanols and their derivatives. Meanwhile this manuscript also explores the reaction of amidines with different carbene precursors, for example diazo compounds, azide, triazoles, pyriodotriazoles, and sulfoxonium ylides as well as their own C-H bond activation/cyclization reactions. A bright outlook is provided at the end of the manuscript.

Construction of isoxazolone-fused phenanthridines via Rh-catalyzed cascade C-H activation/cyclization of 3-arylisoxazolones with cyclic 2-diazo-1,3-diketones.

A Rh(iii)-catalyzed cascade C-H activation/intramolecular cyclization of 3-aryl-5-isoxazolones with cyclic 2-diazo-1,3-diketones was described, leading to the formation of isoxazolo[2,3-f]phenanthridine skeletons. The protocol features the simultaneous one-pot formation of two new C-C/C-N bonds and one heterocycle in moderate-to-good yields with good functional group compatibility. It is amenable to large-scale synthesis and further transformation.

Rh-Catalyzed C-H activation/intramolecular condensation for the construction of benzo[f]pyrazolo[1,5-a][1,3]diazepines.

A novel and mild Rh(iii)-catalyzed C-H activation/intramolecular condensation of 1-aryl-1H-pyrazol-5-amines with cyclic 2-diazo-1,3-diketones was developed, giving access to various important benzo[f]pyrazolo[1,5-a][1,3]diazepine scaffolds through sequential C-C/C-N bond formation in a one-pot procedure under additive- and oxidant-free conditions. Furthermore, 3-([1,1'-biphenyl]-2-ylamino)-2-ethoxycyclohex-2-enones can be obtained in good yields by constructing C-O and C-N bonds through 1,1'-insertion, dehydration, and isomerization processes.

Catalyst-Free Synthesis of 2,3-Dihydrobenzofurans via a Formal [4+1] Annulation of Propargylamines with Sulfur Ylides.

A simple, general route to the 2,3-dihydrobenzofurans substituted at C3 by an aryethynyl or aryl group, starting from propargylamine and its derivatives with benzoyl sulfonium salts, has been developed. This reaction involved an in situ generated o-quinone methide (o-QM) intermediate followed by [4+1] annulation with sulfur ylides. Notably, this protocol's features include moderate to excellent yields and remarkable diastereoselectivity (>20:1 dr in general), easy performance, as well as applicability to versatile 2,3-dihydrobenzofurans with aryethynyl or an aryl group via C-C and C-O bond formation in one pot without any catalyst in an aqueous mixed solvent.

Substituent-oriented C-N bond formation via N-H insertion or Wolff rearrangement of 5-aryl-1H-pyrazoles and diazo compounds.

A facile and efficient synthetic strategy for the chemoselective synthesis of N-substituted 3-aryl-1H-pyrazole derivatives has been developed, and it was oriented by different 2-diazo compounds. Both N-H insertion and Wolff-rearrangement products can be obtained selectively by the opportune choice of diazo compounds. N-Cyclohexenone 3-aryl-1H-pyrazoles were formed using cyclic 2-diazo-1,3-diketones via N-H insertion in the presence of a copper catalyst, and α-carbonyl 3-aryl-1H-pyrazoles could be synthesized through a Wolff-rearrangement process without any catalyst under thermal conditions. Moreover, both reactions could be carried out in moderate to excellent yields (58-93%) and showed good functional group tolerance.

Synthesis of 4-styrylcoumarins via FeCl3-promoted cascade reactions of propargylamines with ß-keto esters.

A versatile and highly regioselective FeCl3-promoted tandem cyclization reaction of in situ generated alkynyl o-quinone methides (o-AQMs) with ß-keto esters has been developed on the basis of the mode involving an intermolecular 1,4-conjugate addition/alkyne-allene isomerization/intramolecular transesterification/isomerization cascade. Using this method, a variety of diversely substituted 4-styryl-2H-chromen-2-ones were prepared with good efficiency and exclusive site-selectivity.

Selective Synthesis of Aminoisoquinolines via Rh(III)-Catalyzed C-H/N-H Bond Functionalization of N-Aryl Amidines with Cyclic 2-Diazo-1,3-diketones.

A simple C-H/N-H bond functionalization of N-aryl amidines with cyclic 2-diazo-1,3-diketones for the synthesis of 1-aminoisoquinolines has been accomplished by employing [Cp*RhCl2]2/CsOPiv as the catalyst system. This methodology proceeds by a cascade C-H activation/intramolecular cyclization under mild reaction conditions, features a broad substrate scope, and involves the formation of two new σ bonds (C-C and C-N) in a single operation for the construction of novel 1-aminoisoquinoline skeletons in good to excellent yields.

Synthesis of Isocoumarins from Cyclic 2-Diazo-1,3-diketones and Benzoic Acids via Rh(III)-Catalyzed C-H Activation and Esterification.

A mild and efficient Rh(III)-catalyzed C-H activation/esterification reaction for the synthesis of isocoumarins has been developed. This procedure uses readily available benzoic acids and cyclic diazo-1,3-diketones as starting materials and involves domino intermolecular C-H activation in combination with intramolecular esterification to give the corresponding isocoumarins in moderate to excellent yields. This process provides a facile approach for the construction of isocoumarins containing various functional groups that does not require any additives.

Direct carboxamidation of cyclic 2-diazo-1,3-diketones by Rh2(OAc)4-catalyzed isocyanide insertion-hydrolysis.

A novel and efficient strategy for the synthesis of 2-hydroxy-6-oxocyclohex-1-enecarboxamides through a Rh2(OAc)4-catalyzed direct carboxamidation of cyclic 2-diazo-1,3-diketones has been developed. The method features readily available starting materials, easy scalability, mild reaction conditions and a simple work-up for product isolation, which makes this strategy highly attractive. A tentative mechanism involving an isocyanide insertion and hydrolysis sequence for this reaction is proposed.

Ir(iii)/Ag(i)-catalyzed directly C-H amidation of arenes with OH-free hydroxyamides as amidating agents.

A versatile Ir(iii)-catalyzed C-H amidation of arenes by employing readily available and stable OH-free hydroxyamides as a novel amidation source. The reaction occurred with high efficiency and tolerance of a range of functional groups. A wide scope of aryl OH-free hydroxyzamides, including conjugated and challenging non-conjugated OH-free hydroxyzamides, were capable of this transformation and no addition of an external oxidant is required. This protocol provided a simple, straightforward and economic method to a variety N-(2-(1H-pyrazol-1-yl)alkyl)amide derivates with good to excellent yield. Mechanistic study demonstrated that reversible C-H bond functionalisation might be involved in this reaction.

Palladium-Catalyzed Cascade Decarboxylative Amination/6-endo-dig Benzannulation of o-Alkynylarylketones with N-Hydroxyamides To Access Diverse 1-Naphthylamine Derivatives.

An efficient and practical one-pot strategy to produce highly substituted 1-naphthylamines via sequential palladium-catalyzed decarboxylative amination/intramolecular 6-endo-dig benzannulation reactions has been described. In this reaction, a broad range of electron-rich, electron-neutral, and electron-deficient o-alkynylarylketones react well with N-hydroxyl aryl/alkylamides to give a diversity of 1-naphthylamines in good to excellent yields under mild reaction conditions. The gram-scale synthesis, with benefits such as undiminished product yield and easy transformation, illustrated the practicality of this method.

Rh(III)-Catalyzed Relay Double Carbenoid Insertion and Diannulation of Sulfoximine Benzamides with α-Diazo Carbonyl Compounds: Access to Furo[2,3-c]isochromenes.

An efficient rhodium-catalyzed construction of furo[2,3-c]isochromene scaffolds through tandem double carbenoid insertion and diannulation of sulfoximine benzamides with α-diazo carbonyl compounds has been developed. Mechanistic studies revealed that the alkyl-rhodium intermediate generated by carbenoid insertion was directly trapped with another molecule of carbene species, followed by subsequent intramolecular cyclization reactions. Sulfoximine was released in situ, featuring a traceless directing fashion. The reactions proceeded smoothly under mild conditions with wide functional group tolerance.

Rh(III)-Catalyzed C-H Activation/Intramolecular Cyclization: Access to N-Acyl-2,3-dihydro-1H-carbazol-4(9H)-ones from Cyclic 2-Diazo-1,3-diketones and N-Arylamides.

A Rh(III)-catalyzed C-H activation/cyclization cascade reaction is described. The reaction involves cyclic 2-diazo-1,3-diketones and N-arylamides, and it proceeds via an intermolecular C-C bond formation and subsequent intramolecular C-N bond formation. A variety of N-acyl-2,3-dihydro-1H-carbazol-4(9H)-ones were obtained under mild conditions in good to excellent yields (65-90%). Key features of this strategy include high-efficiency, operational simplicity, scalability, and broad functional-group tolerance. In addition, H2O and N2 are the only byproducts. Carbazole derivatives with free NH groups can be easily obtained through N-deprotection reactions.

Synthesis of 2-Arylimino-6,7-dihydrobenzo[d][1,3]oxathiol-4(5H)-ones via Rh2(OAc)4-Catalyzed Reactions of Cyclic 2-Diazo-1,3-diketones with Aryl Isothiocyanates.

A convenient and efficient synthesis of 2-arylimino-6,7-dihydrobenzo[d][1,3]oxathiol-4(5H)-ones was developed via a Rh2(OAc)4-catalyzed reaction of cyclic 2-diazo-1,3-diketones and aryl isothiocyanates in acetone at 60 °C. This reaction uses readily available stable cyclic 2-diazo-1,3-diketones as a starting material and generates the desired products in good to excellent yields (78-93%). The reaction proceeds under mild reaction conditions, produces only N2 as the byproduct, and features a broad substrate scope. A plausible mechanism for this reaction is also discussed.