Exploring Cuneanes as Potential Benzene Isosteres and Energetic Materials: Scope and Mechanistic Investigations into Regioselective Rearrangements from Cubanes.

Cuneane is a strained hydrocarbon that can be accessed via metal-catalyzed isomerization of cubane. The carbon atoms of cuneane define a polyhedron of the C2v point group with six faces─two triangular, two quadrilateral, and two pentagonal. The rigidity, strain, and unique exit vectors of the cuneane skeleton make it a potential scaffold of interest for the synthesis of functional small molecules and materials. However, the limited previous synthetic efforts toward cuneanes have focused on monosubstituted or redundantly substituted systems such as permethylated, perfluorinated, and bis(hydroxymethylated) cuneanes. Such compounds, particularly rotationally symmetric redundantly substituted cuneanes, have limited potential as building blocks for the synthesis of complex molecules. Reliable, predictable, and selective syntheses of polysubstituted cuneanes bearing more complex substitution patterns would facilitate the study of this ring system in myriad applications. Herein, we report the regioselective, AgI-catalyzed isomerization of asymmetrically 1,4-disubstituted cubanes to cuneanes. In-depth DFT calculations provide a charge-controlled regioselectivity model, and direct dynamics simulations indicate that the nonclassical carbocation invoked is short-lived and dynamic effects augment the charge model.

Expansion of Azulenes as Nonbenzenoid Aromatic Compounds for C-H Activation: Rhodium- and Iridium-Catalyzed Oxidative Cyclization of Azulene Carboxylic Acids with Alkynes for the Synthesis of Azulenolactones and Benzoazulenes.

Rhodium-catalyzed oxidative [4 + 2] cyclization reactions through the C-H activation of azulene carboxylic acids as nonbenzenoid aromatic compounds with symmetrical and unsymmetrical alkynes were developed under aerobic conditions, which produced azulenolactone derivatives with a wide substrate scope and excellent functional group tolerance. Interestingly, azulenic acids in reaction with alkynes underwent iridium-catalyzed [2 + 2 + 2] cyclization accompanied by decarboxylation to afford tetra(aryl)-substituted benzoazulene derivatives. The reactivity order for C-H activation reaction is greater toward azulene-6-carboxylic acid, azulene-1-carboxylic acid, and azulene-2-carboxylic acid. For the first time, the expansion of azulenes having directing group as nonbenzenoid aromatic compounds for C-H activation was successful, indicating that nonbenzenoid aromatic compounds can be used as good substrates for the C-H activation reaction. Therefore, the research area of C-H activation will certainly expand to nonbenzenoid aromatic compounds in future.

Selective C-C bond formation from rhodium-catalyzed C-H activation reaction of 2-arylpyridines with 3-aryl-2H-azirines.

A novel method for the synthesis of acylmethyl-substituted 2-arylpyridine derivatives using 3-aryl-2H-azirines was developed by exploring a prototype reaction using DFT-calculations and carrying out targeted experiments guided by the calculated mechanism. 2H-Azirine was initially hypothesized to ring-open at the metal center to furnish familiar metal nitrene complexes that may undergo C-N coupling. Computational studies quickly revealed and prototype experimental work confirmed that neither the formation of the expected metal nitrene complexes nor the C-N coupling were viable. Instead, azirine ring-opening followed by C-C coupling was found to be much more favorable to give imines that readily underwent hydrolysis in aqueous conditions to form acylmethyl-substituted products. This new method was highly versatile and selective toward a wide range of substrates with high functional group tolerance. The utility of the new method is demonstrated by a convenient one-pot synthesis of biologically relevant heterocycles such as pyridoisoindole and pyridoisoqunolinone.

One-Pot Synthesis of Indolizines via Sequential Rhodium-Catalyzed [2 + 1]-Cyclopropanation, Palladium-Catalyzed Ring Expansion, and Oxidation Reactions from Pyridotriazoles and 1,3-Dienes.

An efficient, one-pot synthetic method for producing functionalized indolizine derivatives was developed via a Rh-catalyzed [2 + 1]-cyclopropanation, Pd-catalyzed ring expansion, and subsequent oxidation using manganese dioxide from pyridotriazoles and 1,3-dienes.

Synthesis of Imidazopyridines via Copper-Catalyzed, Formal Aza-[3 + 2] Cycloaddition Reaction of Pyridine Derivatives with α-Diazo Oxime Ethers.

The Cu-catalyzed, formal aza-[3 + 2] cycloaddition reaction of pyridine derivatives with α-diazo oxime ethers in trifluoroethanol was used to synthesize imidazopyridines via the release of molecular nitrogen and elimination of alcohol. These methods enabled modular synthesis of a wide range of N-heterobicyclic compounds such as imidazopyridazines, imidazopyrimidines, and imidazopyrazines with an α-imino Cu-carbenoid generated from the α-diazo oxime ethers and copper.

Synthesis of Multisubstituted Allenes, Furans, and Pyrroles via Tandem Palladium-Catalyzed Substitution and Cycloisomerization.

A palladium-catalyzed propargyl substitution reaction of propargyl acetates with indium organothiolates is developed for the synthesis of multisubstituted allenyl sulfides. This procedure can be applied to the synthesis of multisubstituted furans and pyrroles via tandem palladium-catalyzed propargyl substitution and cycloisomerization reaction in one pot.

Synthesis of Benzofulvenes through Rhodium-Catalyzed Transannulation of Enynyl Triazoles.

Rhodium-catalyzed denitrogenative cyclization of (E)-ethyl 2-(1-alkyl and arylsulfonyl-1H-1,2,3-triazol-4-yl)-3-aryl acrylate generated from (E)-ethyl 2-benzylidenebut-3-ynoates and N-sulfonyl azides in the presence of a copper catalyst was developed for the synthesis of a large number of functionalized benzofulvenes. Moreover, the synthesis of benzofulvenes was demonstrated as a one-pot method through tandem copper-catalyzed [3 + 2] cycloaddition and rhodium-catalyzed denitrogenative cyclization from (E)-ethyl 2-benzylidenebut-3-ynoates and N-sulfonyl azides.

Regioselective Synthesis of Dihydrothiophenes and Thiophenes via the Rhodium-Catalyzed Transannulation of 1,2,3-Thiadiazoles with Alkenes.

A method for the regioselective synthesis of a wide range of dihydrothiophenes was developed from the rhodium-catalyzed transannulation of 1,2,3-thiadiazoles with aliphatic, aromatic, and heteroaromatic alkenes. Tandem rhodium-catalyzed transannulation of 1,2,3-thiadiazoles with alkenes followed by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) oxidation was also demonstrated for the one-pot regioselective synthesis of various thiophenes. Advantages of the present method include a broad substrate scope, wide functional group compatibility, and high regioselectivity.

Selective Rhodium-Catalyzed C-H Amidation of Azobenzenes with Dioxazolones under Mild Conditions.

A synthetic method for a wide range of amidated azobenzenes is developed from the selective rhodium-catalyzed C-H amidation reaction of symmetrical as well as unsymmetrical azobenzenes with alkyl-, aryl-, and heteroaryl-substituted dioxazolones under mild conditions. Diamidation of azobenzenes and amidation of monoamidated azobenzenes were also demonstrated.

Synthesis of 1,2-Benzothiazines by a Rhodium-Catalyzed Domino C-H Activation/Cyclization/Elimination Process from S-Aryl Sulfoximines and Pyridotriazoles.

A method for the synthesis of a large number of 1,2-benzothiazines bearing pyridyl as well as carbonyl groups is developed from rhodium-catalyzed carbene insertions into aromatic C-H bonds of S-aryl sulfoximines using pyridotriazoles by denitrogenative cyclization followed by the elimination of alcohols. The present method involves the N-H/C-H activation of simple alkyl aryl sulfoximines and has the advantages of a broad substrate scope, high functional group tolerance, and good regioselectivity.

Synthesis of 2-Alkoxyaryl-2-aryl Enamines via Tandem Copper-Catalyzed Cycloaddition and Rhodium-Catalyzed Alkoxyarylation from Alkynes, N-Sulfonyl Azides, and Aryl Ethers.

A synthetic route to a wide range of 2-alkoxyaryl-2-aryl enamines is developed from Rh-catalyzed alkoxyarylation of N-sulfonyl-4-aryl-1,2,3-triazoles with aryl ethers via the elimination of nitrogen molecule. In addition, 2-alkoxyaryl-2-aryl enamines are prepared via tandem Cu-catalyzed cycloaddition and Rh-catalyzed alkoxyarylation starting from alkynes, N-sulfonyl azides, and aryl ethers in one-pot.

Synthesis of Cinnolin-3(2H)-one Derivatives from Rh-Catalyzed Reaction of Azobenzenes with Diazotized Meldrum's Acid.

A synthetic method of a wide range of cinnolin-3(2H)-one derivatives is developed from the reaction of symmetrical as well as unsymmetrical azobenzenes with diazotized Meldrum's acid via Rh-catalyzed C-H alkylation followed by cyclization.

Synthesis of 2-bromoimidazoles from alkynes, N-sulfonylazides, and bromocyanides.

A synthetic method for 2-bromoimidazoles is developed from Rh-catalyzed cyclization of N-sulfonyl-1,2,3-triazoles with bromocyanides. Cu-catalyzed [3 + 2] cycloaddition followed by Rh-catalyzed cyclization starting from alkynes, N-sulfonylazides, and bromocyanides is also demonstrated for de novo synthesis of 2-bromoimidazoles in one pot. Moreover, this work was successfully employed to introduce diverse functional groups to the 2-position of imidazoles via cross-coupling reaction.

Alkenylation of phosphacoumarins via aerobic oxidative Heck reactions and their synthetic application to fluorescent benzophosphacoumarins.

Alkenylation of phosphacoumarins is developed from the reaction of phosphacoumarins with a variety of activated as well as nonactivated alkenes via aerobic oxidative Heck reactions. In addition, 3-alkenylphosphacoumarins undergo an inverse electron demand Diels-Alder reaction (IEDDA) with enamines in situ generated from ketone and pyrrolidine followed by 1,2-elimination and a dehydrogenation, producing fluorescent benzophosphacoumarins.

Rhodium-catalyzed oxidative coupling through C-H activation and annulation directed by phosphonamide and phosphinamide groups.

Rhodium-catalyzed oxidative coupling reactions via C-H activation and annulation directed by phosphonamide and phosphinamide groups were developed under aerobic conditions, which produced benzazaphosphole 1-oxides and phosphaisoquinolin-1-oxides.