Modular Assembly of Pyrrolo[3,4-c]isoquinolines through Rh-Catalyzed Cascade C-H Activation/Annulation of O-Methyl Aryloximes with Maleimides.

An efficient and practical strategy for the construction of pyrrolo[3,4-c]isoquinolines via Rh(III)-catalyzed cascade C-H activation and subsequential annulation process from easily available O-methyl aryloximes and maleimides has been disclosed. This facile protocol does not require any inert atmosphere protection with good efficiency in a low loading of catalyst and exhibits good functional group tolerance and broad substrate scope. Notably, the as-prepared products show potential photophysical properties.

Base-Mediated Cascade Lactonization/1,3-Dipolar Cycloaddition Pathway for the One-Pot Assembly of Coumarin-Functionalized Pyrrolo[2,1-a]isoquinolines.

An elegant and highly concise strategy for the construction of coumarin-functionalized pyrrolo[2,1-a]isoquinolines from available propargylamines and isoquinolinium N-ylides has been disclosed. In this reaction, isoquinolinium N-ylides acted as a C2 synthon to form a coumarin ring as well as a 1,3-dipole to construct a pyrrole ring in a single pot. This cascade process involves 1,4-conjugate addition/lactonization/1,3-dipolar cycloaddition to construct four chemical bonds (one C-O bond and three C-C bonds) and two new heterocyclic skeletons. Additionally, most of these compounds showed good fluorescence properties and exhibited high molar extinction coefficient and large Stokes shifts.

A rhodium-catalyzed cascade C-H activation/annulation strategy for the expeditious assembly of pyrrolidinedione-fused 1,2-benzothiazines.

A cascade annulation strategy triggered by rhodium(III)-catalyzed C-H activation has been reported for the expeditious assembly of pyrrolidinedione-fused 1,2-benzothiazines from free NH-sulfoximines with maleimides under mild conditions. Without the need for inert atmosphere protection, a broad range of sulfoximines with maleimides were well tolerated, producing diverse fused-thiazine derivatives in moderate to good yields. Additionally, the late-stage transformation of the target product demonstrated the potential synthetic value of this protocol.

Construction of C-S and C-Se Bonds from Unstrained Ketone Precursors under Photoredox Catalysis.

A mild photoredox catalyzed construction of sulfides, disulfides, selenides, sulfoxides and sulfones from unstrained ketone precursors is introduced. Combination of this deacylative process with SN 2 or coupling reactions provides novel and convenient modular strategies toward unsymmetrical or symmetric disulfides. Reactivity studies favor a bromine radical that initiates a HAT (Hydrogen Atom Transfer) from the aminal intermediate resulting in expulsion of a C-centered radical that is intercepted to make C-S and C-Se bonds. Gram scale reactions, broad substrate scope and tolerance towards various functional groups render this method appealing for future applications in the synthesis of organosulfur and selenium complexes.

Cascade Annulation Strategy for Expeditious Assembly of Hydroxybenzo[c]chromen-6-ones and Their Photophysical Property Studies.

A 1,8-diazabicyclo[5.4.0]undec-7-ene-promoted cascade double-annulation of ortho-alkynyl quinone methide (in situ generated from modular propargylamine) for constructing of 2-aryl-4-hydroxybenzo[c]chromen-6-ones is developed. This synthetic strategy offers remarkable operational simplicity as it allows the use of benchtop-grade solvents without the need for predrying measures and inert atmosphere protection. Additionally, it demonstrates good functional group compatibility. The photophysical properties of these compounds were also examined, revealing bright fluorescence with high quantum yields.

Base-promoted tandem synthesis of 2-azaaryl indoline.

A novel tandem method to synthesize 2-azaaryl indoline promoted by LiN(SiMe3)2 from 2-azaaryl methyl amine and 2-fluoro benzyl bromides was developed. Mechanistic investigation indicated that this tandem cyclization was initiated by selective benzyl C-SN2 substitution followed by an intramolecular SNAr reaction. Diverse 2-azaaryl indoles could also be obtained via simple functional transformations.

Synthesis of arene-functionalized fused heterocyclic scaffolds via a regioselective cascade 1,4-conjugate addition/5-exo-dig annulation strategy.

Facile access to furan fused heterocyclic scaffolds through a regioselective cascade reaction of propargylamines with 4-hydroxy-2H-pyran-2-ones and 4-hydroxy-6-methylpyridin-2(1H)-one has been achieved. This cascade reaction presumably involves the formation of ortho-alkynyl quinone methide (o-AQM), 1,4-conjugate addition, followed by regioselective 5-exo-dig annulation, and a 1,3-H shift process. Moreover, the reaction provides a new and efficient method for the synthesis of highly sterically congested 3-phenolic furo[3,2-c]pyran-4-ones and furo[3,2-c]pyridin-4(5H)-ones by the formation of a furan ring from readily available starting materials in good to high yields (50-82%) with broad functional group compatibility in a single step. Significantly, the strategy described here is easily scalable and several useful synthetic transformations of the prepared arene-functionalized 4H-furo[3,2-c]pyran-4-ones were also performed.

Photosensitive damage of dipeptides: mechanism and influence of structure.

We illustrate the influence of the dipeptide structure on photosensitive damage and the kinetic mechanism was investigated using acenaphthenequinone (ACQ) as a triplet photosensitizer. With tyrosine (Tyr) serving as the core structure, two classic dipeptides with double (trptophan-tyrosine, Trp-Tyr) and single (tyrosine-alanine, Tyr-Ala and Ala-Tyr) active reaction sites were constructed, and the underlying photodamage mechanisms were investigated carefully. According to the experimental results, the proton-coupled electron transfer processes between ACQ and numerous Trp-Tyr reaction sites have independent reaction properties. The bimolecular quenching rate (kq) value is roughly equivalent to the sum of the rates of two amino acid monomers, and a novel intramolecular dynamic channel between Trp/N˙-Tyr and Trp-Tyr/O˙ was observed. The ACQ/Tyr-Ala system demonstrated the key role of steric hindrance on the kq in bimolecular reactions.

Radical-Induced Cascade Annulation/Hydrocarbonylation for Construction of 2-Aryl-4H-chromen-4-ones.

A robust metal- and solvent-free cascade radical-induced C-N cleavage/intramolecular 6-endo-dig annulation/hydrocarbonylation for the synthesis of the valuable 2-aryl-4H-chromen-4-ones is described. This practical synthesis strategy utilizes propargylamines and air as the oxygen source and green carbonylation reagent, in which propargylamines are activated by the inexpensive and available dimethyl 2,2'-azobis(2-methylpropionate) (AIBME) and (PhSe)2 as the radical initiators. This simple and green protocol features wide substrate adaptability, good functional group tolerance, and amenability to scaling up and derivatizations.

Rh-Catalyzed Cascade C-H Activation/Annulation of N-Hydroxybenzamides and Propargylic Acetates for Modular Access to Isoquinolones.

A sequential Rh(III)-catalyzed C-H activation/annulation of N-hydroxybenzamides with propargylic acetates leading to the formation of NH-free isoquinolones is described. This reaction proceeds through a sequential C-H activation/alkyne insertion/intramolecular annulation/N-O bond cleavage procedure, affording a broad spectrum of products with diverse substituents in moderate-to-excellent yields. Notably, this protocol features the simultaneous formation of two new C-C/C-N bonds and one heterocycle in one pot with the release of water as the sole byproduct.

Rh(III)-Catalyzed Cascade Nucleophilic Addition/Annulation of 2-Diazo-1,3-diketones with 1,3-Dicarbonyl Compounds To Access 6,7-Dihydrobenzofuran-4(5H)-ones.

A Rh(III)-catalyzed cascade nucleophilic addition/intramolecular annulation of 2-diazo-1,3-diketones with 1,3-dicarbonyl compounds (e.g., 1,3-diketones and ß-keto esters) is achieved to afford 6,7-dihydrobenzofuran-4(5H)-ones in up to 91% yields. Notably, a wide range of substrates and functional groups were well-tolerated under the optimized reaction conditions to give desired products in moderate to excellent yields with release of N2 and H2O as byproducts. Moreover, the method described is scalable and adaptable to late-stage functionalization.

Copper-Catalyzed Cascade 1,4-Addition/Annulation/Hydrolysis of Propargylamines with 2-Hydroxynaphthalene-1,4-diones: Direct Formation of 12-Phenacyl-11H-benzo[b]xanthenes.

A novel and versatile approach to construct 12-phenacyl-11H-benzo[b]xanthene-6,11(12H)-dione derivatives through copper-catalyzed cascade reaction of propargylamines with 2-hydroxynaphthalene-1,4-diones has been developed. The procedure is proposed to go through a sequence of 1,4-conjugate addition, intramolecular nucleophilic addition/dehydration, and hydrolysis of alkyne followed by an enol-ketone tautomerization. The reaction provides a new and highly efficient method for the synthesis of 12-phenacyl-11H-benzo[b]xanthene-6,11(12H)-diones by formation of three new bonds and one heterocycle from readily available starting materials in good to high yields (70-88%) with broad functional group compatibility in a single step.

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.

Palladium-Catalyzed Divergent Imidoylative Cyclization of Multifunctionalized Isocyanides: Tunable Access to Oxazol-5(4H)-ones and Cyclic Ketoimines.

A palladium-catalyzed tunable imidoylative cyclization of multifunctionalized isocyanides to construct diverse imine-containing heterocycles has been developed. Oxazol-5(4H)-one derivatives were obtained exclusively when allyl-2-benzyl(or allyl)-2-isocyanoacetates were used in the reaction with aryl triflates as electrophiles, whereas cyclic ketoimines were generated in the presence of aryl iodides with the allyl ester group remaining unreacted. The reactions proceeded smoothly under mild conditions with a wide functional group tolerance.

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.

Synthesis of unsymmetrical urea derivatives via one-pot sequential three-component reactions of cyclic 2-diazo-1,3-diketones, carbodiimides, and 1,2-dihaloethanes.

A novel and efficient multicomponent reaction of cyclic 2-diazo-1,3-diketones, carbodiimides, and 1,2-dihaloethanes has been developed, and it leads to unsymmetrical urea derivatives with good yields in a single operation. This transformation involves the cascade formation of C-X (X = Cl, Br, I), C-N and C[double bond, length as m-dash]O bonds through halogenation, nucleophilic addition, ring-opening, and enol-ketone tautomerization processes. This protocol is step- and atom-economical; 1,2-dihaloethane was used as an easily available halogenated reagent, and it is amenable to different functional groups.

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.

Controllable construction of isoquinolinedione and isocoumarin scaffolds via RhIII-catalyzed C-H annulation of N-tosylbenzamides with diazo compounds.

A highly efficient protocol for the synthesis of isoquinolinediones by RhIII-catalyzed C-H activation/annulation/decarboxylation of N-tosylbenzamides with diazo compounds is reported. The switchable synthesis of isocoumarins was also achieved successfully via C-H activation/annulation with slight modification of the reaction conditions. Importantly, the synthetic utility of this new reaction was further demonstrated in an atom-economical and operationally convenient total synthesis of a TDP2 inhibitor derivative from commercially available starting materials.

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.

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.