Boshun Wan

Rhodium-Catalyzed C–H Activation of Phenacyl Ammonium Salts Assisted by an Oxidizing C–N Bond: A Combination of Experimental and Theoretical Studies

Rh(III)-catalyzed C-H activation assisted by an oxidizing directing group has evolved to a mild and redox-economic strategy for the construction of heterocycles. Despite the success, these coupling systems are currently limited to cleavage of an oxidizing N-O or N-N bond. Cleavage of an oxidizing C-N bond, which allows for complementary carbocycle synthesis, is unprecedented. In this article, α-ammonium acetophenones with an oxidizing C-N bond have been designed as substrates for Rh(III)-catalyzed C-H activation under redox-neutral conditions. The coupling with α-diazo esters afforded benzocyclopentanones, and the coupling with unactivated alkenes such as styrenes and aliphatic olefins gave ortho-olefinated acetophenoes. In both systems the reactions proceeded with a broad scope, high efficiency, and functional group tolerance. Moreover, efficient one-pot coupling of diazo esters has been realized starting from α-bromoacetophenones and triethylamine. The reaction mechanism for the coupling with diazo esters has been studied by a combination of experimental and theoretical methods. In particular, three distinct mechanistic pathways have been scrutinized by DFT studies, which revealed that the C-H activation occurs via a C-bound enolate-assisted concerted metalation-deprotonation mechanism and is rate-limiting. In subsequent C-C formation steps, the lowest energy pathway involves two rhodium carbene species as key intermediates.

A Simple and Highly Efficient Iron Catalyst for a [2+2+2] Cycloaddition to Form Pyridines†

Transition-metal-catalyzed [2+2+2] cycloaddition reactions that use two alkynes and a nitrile is the most straightforward and powerful strategy for the construction of multisubstituted pyridines with high atom efficiency. 2] The iron-catalyzed [2+2+2] cycloaddition to form pyridines remains a great challenge in this field, 4] although significant efforts have been made in various catalytic systems (e.g. Co, Ru, Rh, Ni, Ti, Zr/Ni) in the last few decades. Guerchais and co-workers described a stoichiometric reaction between an Fe complex (Scheme 1, structure A) and alkynes with a 73 % yield. Meanwhile, Zenneck and co-workers developed a cycloaddition reaction catalyzed by an Fe complex (Scheme 1, structure B), however, this approach gave low chemoselectivity and had a complicated procedure for catalyst preparation. A very recent example revealed that no pyridine products were observed from alkynes under iron catalyst even when nitrile was used as the solvent. Therefore, the development of a simple and highly efficient iron catalyst to exclusively generate pyridine compounds would be a useful contribution to this area. Herein, we disclose the [2+2+2] cycloaddition of diynes and unactivated nitriles at room temperature using a simple iron salt as the catalyst precursor, thus resulting in the production of pyridines with up to 98% yield of isolated product. Two important steps are generally involved in [2+2+2] cycloaddition: 1) formation of a metallacycle intermediate by oxidative cyclization and 2) subsequent reductive elimination to produce pyridines (the “common mechanism”). The formation of a metallacycle intermediate from a low-valent metal species plays a crucial role in the whole process. Inspired by an investigation by Holland and co-workers revealing that alkynes bind more tightly than phosphines to low-valent iron center, we envisioned that low-valent iron catalysts generated in situ from an inorganic iron salt and phosphine ligands might initiate the reaction through ligand exchange, and thereby promote the oxidative cyclization between an alkyne and an alkyne or a nitrile followed by the formation of metallacycle intermediate (Scheme 1, Step 2). Considering that the formation of benzene rings can be somewhat inhibited in the presence of a certain amount of nitrile compounds—the nature of the ligand has a dramatic effect on the reaction product—it is possible to generate pyridines with high efficiency when the appropriate iron salt and ligand are used. Initially, diyne 1 a and benzonitrile 2a were used as model substrates for the optimization of the cycloaddition reaction conditions, and the results are summarized in Table 1. In the first instance, we employed the iron salt FeCl3 as the catalyst precursor, 1,2-bis(diphenylphosphino)ethane (dppe) as the ligand, and 2 a as the solvent (Table 1, entries 1–4). No desired product was observed in the absence of dppe, as expected, and only trace amounts of 3a were obtained when FeCl3/dppe was used as the catalyst in a 1:1 ratio (6 % yield, entry 2). Given that the amount of ligand can strongly affect the catalytic efficiency, different metal/ligand ratios were screened. The yield was dramatically improved to 97% when a 1:2 mixture of metal and ligand was used (entry 3), however, further increasing the ratio to 1:3 drastically decreased the yield (entry 4, 38%). Sequential investigations of other iron salts, solvents, and ligands (entries 5–9) showed that the combination of FeBr2 or FeI2 with 1,3-bis(diphenylphosphino)propane Scheme 1. Iron catalysts used for the [2+2+2] cycloaddition to form pyridines. TMS= trimethylsilyl.

Rhodium(III)-Catalyzed Azacycle-Directed Intermolecular Insertion of Arene C–H Bonds into α-Diazocarbonyl Compounds

Cp*Rh(III)-catalyzed intermolecular C-C couplings between activated α-diazocarbonyl compounds and arenes bearing a range of azacyclic directing groups have been achieved. This catalytic alkylation reaction operates under mild conditions with good functional group tolerance.

Rhodium(III)‐Catalyzed CC Coupling between Arenes and Aziridines by CH Activation

Making C-C from C-H: [{RhCp*Cl(2)}(2)]/AgSbF(6) (Cp*=pentamethylcyclopentadienyl) can regioselectively catalyze the C-C coupling of arenes with aziridines by a C-H activation pathway. An eight-membered rhodacyclic intermediate resulting from the insertion of the Rh-C bond into the aziridine was isolated.

Rhodium(III)-Catalyzed C-H Activation and Amidation of Arenes Using N-Arenesulfonated Imides as Amidating Reagents

Rhodium(III)-catalyzed C-H activation-amidation of arenes bearing chelating groups has been achieved using N-arenesulfonated imides as efficient amidating reagents without using any base additive. Pyridine, oxime, and pyrimidine proved to be viable directing groups.

A highly diastereo- and enantioselective copper(I)-catalyzed Henry reaction using a bis(sulfonamide)-diamine ligand.

A series of bis(sulfonamide)-diamine (BSDA) ligands were synthesized from commercially available chiral α-amino alcohols and diamines. The chiral BSDA ligand 3a, coordinated with Cu(I), catalyzes the enantioselective Henry reaction with excellent enantioselectivity (up to 99%). Moreover, with the assistance of pyridine, a CuBr-3a system promotes the diastereoselective Henry reaction with various aldehyde substrates and gives the corresponding syn-selective adduct with up to a 99% yield and 32.3:1 syn/anti selectivity. The enantiomeric excess of the syn adduct was 97%.

Highly Regioselective Migration of the Sulfonyl Group: Easy Access to Functionalized Pyrroles

The development of new reactions for the synthesis of diverse molecular frameworks is a challenging task in the field of modern organic chemistry. Chemistry of pyrroles continues to attract the interest of chemists, and new synthetic methods of these compounds occupy an important area of synthetic organic chemistry. In search of new routes for the synthesis of pyrroles through the design of new building blocks such as N-sulfonyl-protected azaenyne derivatives 1 (Scheme 1), we

Palladium-catalyzed desulfitative arylation of azoles with arylsulfonyl hydrazides

Palladium-catalyzed desulfitative and denitrogenative arylation of azoles with arylsulfonyl hydrazides has been achieved. A broad scope of azoles and arylsulfonyl hydrazides has been used to produce arylated azoles in high yields.

Rh(III)-Catalyzed Selenylation of Arenes with Selenenyl Chlorides/Diselenides via C–H Activation

Rh(III)-catalyzed, chelation-assisted C-H activation and selenylation of arenes has been achieved. Arenes bearing oxime, azo, pyridyl, and N-oxide chelating groups are viable substrates, and electrophilic selenyl chlorides and diselenides are used as selenylating reagents. The catalytic system is highly efficient under mild conditions over a broad range of substrates with excellent functional group tolerance.

Iron-Catalyzed Cycloaddition Reaction of Diynes and Cyanamides at Room Temperature

An iron-catalyzed [2 + 2 + 2] cycloaddition reaction of diynes and cyanamides at room temperature is reported. Highly substituted 2-aminopyridines were obtained in good to excellent yields with high regioselectivity. Insights toward the reaction process were investigated through in situ IR spectra and control experiments. In this iron-catalyzed cycloaddition reaction, the active iron species was generated only in the presence of both alkynes and nitriles. The lower reaction temperature, broad substrates scope, and inversed regioselectivity make it a complementary method to the previously developed iron catalytic system.