Preparation of Chiral Enantioenriched Densely Substituted Cyclopropyl Azoles, Amines, and Ethers via Formal SN2' Substitution of Bromocylopropanes.

Enantiomerically enriched cyclopropyl ethers, amines, and cyclopropylazole derivatives possessing three stereogenic carbon atoms in a small cycle are obtained via the diastereoselective, formal nucleophilic substitution of chiral, non-racemic bromocyclopropanes. The key feature of this methodology is the utilization of the chiral center of the cyclopropene intermediate, which governs the configuration of the two adjacent stereocenters that are successively installed via 1,4-addition/epimerization sequence.

Cascade Synthesis of Pyrroles from Nitroarenes with Benign Reductants Using a Heterogeneous Cobalt Catalyst.

A bifunctional 3d-metal catalyst for the cascade synthesis of diverse pyrroles from nitroarenes is presented. The optimal catalytic system Co/NGr-C@SiO2 -L is obtained by pyrolysis of a cobalt-impregnated composite followed by subsequent selective leaching. In the presence of this material, (transfer) hydrogenation of easily available nitroarenes and subsequent Paal-Knorr/Clauson-Kass condensation provides >40 pyrroles in good to high yields using dihydrogen, formic acid, or a CO/H2 O mixture (WGSR conditions) as reductant. In addition to the favorable step economy, this straightforward domino process does not require any solvents or external co-catalysts. The general synthetic utility of this methodology was demonstrated on a variety of functionalized substrates including the preparation of biologically active and pharmaceutically relevant compounds, for example, (+)-Isamoltane.

Molecularly Defined Manganese Catalyst for Low-Temperature Hydrogenation of Carbon Monoxide to Methanol.

Methanol synthesis from syngas (CO/H2 mixtures) is one of the largest manmade chemical processes with annual production reaching 100 million tons. The current industrial method proceeds at high temperatures (200-300 °C) and pressures (50-100 atm) using a copper-zinc-based heterogeneous catalyst. In contrast, here, we report a molecularly defined manganese catalyst that allows for low-temperature/low-pressure (120-150 °C, 50 bar) carbon monoxide hydrogenation to methanol. This new approach was evaluated and optimized by quantum mechanical simulations virtual high-throughput screenings. Crucial for this achievement is the use of amine-based promoters, which capture carbon monoxide to give formamide intermediates, which then undergo manganese-catalyzed hydrogenolysis, regenerating the promoter. Following this conceptually new approach, high selectivity toward methanol and catalyst turnover numbers (up to 3170) was achieved. The proposed general catalytic cycle for methanol synthesis is supported by model studies and detailed spectroscopic investigations.

Organoselenium-catalyzed enantioselective syn-dichlorination of unbiased alkenes.

The enantioselective dichlorination of alkenes is a continuing challenge in organic synthesis owing to the limitations of selective and independent antarafacial delivery of both electrophilic chlorenium and nucleophilic chloride to an olefin. Development of a general method for the enantioselective dichlorination of isolated alkenes would allow access to a wide variety of polyhalogenated natural products. Accordingly, the enantioselective suprafacial dichlorination of alkenes catalyzed by electrophilic organoselenium reagents has been developed to address these limitations. The evaluation of twenty-three diselenides as precatalysts for enantioselective dichlorination is described, with a maximum e.r. of 76:24 Additionally, mechanistic studies suggest an unexpected Dynamic Kinetic Asymmetric Transformation (DyKAT) process may be operative.

Toward Catalytic, Enantioselective Chlorolactonization of 1,2-Disubstituted Styrenyl Carboxylic Acids.

An investigation into the use of Lewis base catalysis for the enantioselective chlorolactonization of 1,2-disubstituted alkenoic acids is described. Two mechanistically distinct reaction pathways for catalytic chlorolactonization have been identified. Mechanistic investigation revealed that tertiary amines predominately operate as Brønsted rather than Lewis bases. Two potential modes of activation have been identified that involve donation of electron density of the carboxylate to the C═C bond as well hydrogen bonding to the chlorinating agent. Sulfur- and selenium-based additives operate under Lewis base catalysis; however, due to the instability of the intermediate benzylic chloriranium ion, chlorolactonization suffers from low chemo-, diastereo-, and enantioselectivities. Independent generation of the benzylic chloriranium ion shows that it is in equilibrium with an open cation, which leads to low specificities in the nucleophilic capture of the intermediate.

Formal substitution of bromocyclopropanes with nitrogen nucleophiles.

A highly chemo- and diastereoselective protocol toward amino-substituted donor-acceptor cyclopropanes via the formal nucleophilic displacement in bromocyclopropanes is described. A wide range of N-nucleophiles, including carboxamides, sulfonamides, azoles, and anilines, can be efficiently employed in this transformation, providing expeditious access to stereochemically defined and densely functionalized cyclopropylamine derivatives.

A Convenient and Stable Heterogeneous Nickel Catalyst for Hydrodehalogenation of Aryl Halides Using Molecular Hydrogen.

Invited for this month's cover is the group of Matthias Beller at the Leibniz Institute for Catalysis in Rostock in collaboration with Muhammad Anwar and Sarim Dastgir at the Qatar Environment and Energy Research Institute in Doha. The image illustrates a hydrodehalogenation of polybrominated diphenyl ether (PBDE) using a heterogeneous nickel catalyst supported on titanium oxide and dihydrogen. The Research Article itself is available at 10.1002/cssc.202102315.

A Convenient and Stable Heterogeneous Nickel Catalyst for Hydrodehalogenation of Aryl Halides Using Molecular Hydrogen.

Hydrodehalogenation is an effective strategy for transforming persistent and potentially toxic organohalides into their more benign congeners. Common methods utilize Pd/C or Raney-nickel as catalysts, which are either expensive or have safety concerns. In this study, a nickel-based catalyst supported on titania (Ni-phen@TiO2 -800) is used as a safe alternative to pyrophoric Raney-nickel. The catalyst is prepared in a straightforward fashion by deposition of nickel(II)/1,10-phenanthroline on titania, followed by pyrolysis. The catalytic material, which was characterized by SEM, TEM, XRD, and XPS, consists of nickel nanoparticles covered with N-doped carbon layers. By using design of experiments (DoE), this nanostructured catalyst is found to be proficient for the facile and selective hydrodehalogenation of a diverse range of substrates bearing C-I, C-Br, or C-Cl bonds (>30 examples). The practicality of this catalyst system is demonstrated by the dehalogenation of environmentally hazardous and polyhalogenated substrates atrazine, tetrabromobisphenol A, tetrachlorobenzene, and a polybrominated diphenyl ether (PBDE).

Heterogeneous nickel-catalysed reversible, acceptorless dehydrogenation of N-heterocycles for hydrogen storage.

Nickel-based nanocatalysts were used in acceptorless, reversible dehydrogenation and hydrogenation reactions of N-heterocycles. Both processes were realized in the same solvent using a single catalyst, without isolation of products and workup, which makes it attractive for hydrogen storage purposes. This concept has been demonstrated in a continuous hydrogenation/dehydrogenation sequence of quinaldine with negligible loss in activity of the nickel catalyst after three hydrogen storage cycles. The scope of acceptorless dehydrogenation has been explored and control experiments suggest that hydrogen liberation is initiated via amine dehydrogenation and supports the direct alkane dehydrogenation from the partially oxidized N-heterocycles.

Intermetallic nickel silicide nanocatalyst-A non-noble metal-based general hydrogenation catalyst.

Hydrogenation reactions are essential processes in the chemical industry, giving access to a variety of valuable compounds including fine chemicals, agrochemicals, and pharmachemicals. On an industrial scale, hydrogenations are typically performed with precious metal catalysts or with base metal catalysts, such as Raney nickel, which requires special handling due to its pyrophoric nature. We report a stable and highly active intermetallic nickel silicide catalyst that can be used for hydrogenations of a wide range of unsaturated compounds. The catalyst is prepared via a straightforward procedure using SiO2 as the silicon atom source. The process involves thermal reduction of Si-O bonds in the presence of Ni nanoparticles at temperatures below 1000°C. The presence of silicon as a secondary component in the nickel metal lattice plays the key role in its properties and is of crucial importance for improved catalytic activity. This novel catalyst allows for efficient reduction of nitroarenes, carbonyls, nitriles, N-containing heterocycles, and unsaturated carbon-carbon bonds. Moreover, the reported catalyst can be used for oxidation reactions in the presence of molecular oxygen and is capable of promoting acceptorless dehydrogenation of unsaturated N-containing heterocycles, opening avenues for H2 storage in organic compounds. The generality of the nickel silicide catalyst is demonstrated in the hydrogenation of over a hundred of structurally diverse unsaturated compounds. The wide application scope and high catalytic activity of this novel catalyst make it a nice alternative to known general hydrogenation catalysts, such as Raney nickel and noble metal-based catalysts.

Templated Assembly of Chiral Medium-Sized Cyclic Ethers via 8-endo-trig Nucleophilic Cyclization of Cyclopropenes.

An efficient approach toward enantioenriched eight-membered heterocycles via the intramolecular formal substitution of bromocyclopropanes with oxygen-based nucleophiles has been developed. The reaction proceeds via a reactive cyclopropene intermediate, which undergoes a rapid 8-endo-trig cyclization affording cis-fused [6.1.0] bicyclic products exclusively. The quaternary chiral center in the cyclopropene governs the configuration of the other two stereocenters in the final product.

Dual control of the selectivity in the formal nucleophilic substitution of bromocyclopropanes en route to densely functionalized, chirally rich cyclopropyl derivatives.

Densely substituted cyclopropanol and cyclopropylazole derivatives with three stereogenic carbons in the small cycle are obtained via a highly diastereoselective formal nucleophilic substitution of bromocyclopropanes. The chiral center at C-2 in bromocyclopropane dictates the configuration of the other two stereocenters that are successively installed via a sterically controlled addition of a nucleophile, followed by a thermodynamically driven epimerization of the resulting enolate intermediate.

Formal nucleophilic substitution of bromocyclopropanes with azoles.

A highly diastereoselective protocol for the formal nucleophilic substitution of 2-bromocyclopropylcarboxamides with azoles is described. A wide range of azoles, including pyrroles, indoles, benzimidazoles, pyrazoles, and benzotriazoles, can be efficiently employed as pronucleophiles in this transformation, providing expeditious access to N-cyclopropyl heterocycles.