Luminescent Hydride-Free [Cu7(SC5H9)7(PPh3)3] Nanocluster: Facilitating Highly Selective C-C Bond Formation.

Amidst burgeoning interest, atomically precise copper nanoclusters (Cu NCs) have emerged as a remarkable class of nanomaterials distinguished by their unparalleled reactivity. Nonetheless, the synthesis of hydride-free Cu NCs and their role as stable catalysts remain infrequently explored. Here, we introduce a facile synthetic approach to fabricate a hydride-free [Cu7(SC5H9)7(PPh3)3] (Cu7) NC and delineate its photophysical properties intertwined with their structural configuration. Moreover, the utilization of its photophysical properties in a photoinduced C-C coupling reaction demonstrates remarkable specificity toward cross-coupling products with high yields. The combined experimental and theoretical investigation reveals a nonradical mechanistic pathway distinct from its counterparts, offering promising prospects for designing hydride-free Cu NC catalysts in the future and unveiling the selectivity of the hydride-free [Cu7(SC5H9)7(PPh3)3] NC in photoinduced Sonogashira C-C coupling through a polar reaction pathway.

Kinetically-Controlled Ni-Catalyzed Direct Carboxylation of Unactivated Secondary Alkyl Bromides without Chain Walking.

Herein, we report the direct carboxylation of unactivated secondary alkyl bromides enabled by the merger of photoredox and nickel catalysis, a previously inaccessible endeavor in the carboxylation arena. Site-selectivity is dictated by a kinetically controlled insertion of CO2 at the initial C(sp3)-Br site by the rapid formation of Ni(I)-alkyl species, thus avoiding undesired ß-hydride elimination and chain-walking processes. Preliminary mechanistic experiments reveal the subtleties of stereoelectronic effects for guiding the reactivity and site-selectivity.

Synthesis of Unsymmetrical 3,3'-Dialkyloxindole Boronic Esters from 3-Alkylidene-2-oxindoles Enabled by Copper Catalysis.

We describe a 1,2-alkylboration of 3-alkylidene-2-oxindoles with a diboron reagent and alkyl bromides and iodides enabled by copper/bisphosphine catalysis. This scalable alkylboration method provides facile access to 3,3'-dialkyloxindole boronic esters featuring an all-carbon quaternary stereocenter and an increased F(sp3) fraction. In addition to good functional group tolerance and prolific utilization of drug/pesticide-derived alkyl iodides, the conversion of the C-B bond to a C-C/C-X bond offers further opportunities for structural variation of 3,3'-dialkyloxindoles.

Photocatalytic Alkylation/Arylative Cyclization of N-Acrylamides of N-Heteroarenes and Arylamines with Dihydroquinazolinones from Unactivated Ketones.

We describe a visible-light photoredox-catalyzed alkylation/arylative cyclization of N-acrylamides─from 2-arylindoles, 2-arylbenzimidazoles, or N-substituted anilines─with ketone-derived dihydroquinazolinones, accessing indolo- and benzimidazolo[2,1-a]isoquinolines or 2-oxindoles. The consecutive incorporation of alkyl- and aryl-carbogenic motifs across a C=C bond via formal cleavage of ketone α-C-C and arene C-H bonds leads to the formation of five- and six-membered rings, with an all-carbon quaternary stereocenter. This dicarbofunctionalization elaborates aromatization-driven radical C-C functionalization of unactivated aliphatic ketones to construct diverse cyclic structures with functionality tolerance.

Utilization of CO2 Feedstock for Organic Synthesis by Visible-Light Photoredox Catalysis.

CO2 is a highly abundant, green, and sustainable carbon feedstock. Despite its kinetic inertness and thermodynamic stability, the development of various catalytic techniques has enabled the conversion of CO2 to value-added products such as carboxylic acids, amino acids, and heterocyclic compounds, where visible-light photocatalysis has emerged to be an efficient promoter of these processes. This Minireview covers the progress in the areas of CO2 incorporation onto organic matters based on the combined venture of renewable resources of CO2 and light energy with significant emphasis on the last three years' developments.

Remote sp2 C-H Carboxylation via Catalytic 1,4-Ni Migration with CO2.

A remote catalytic reductive sp2 C-H carboxylation of arenes with CO2 (1 bar) via 1,4-Ni migration is disclosed. This protocol constitutes the first catalytic 1,4-Ni migration reported to date, thus offering new vistas in the Ni-catalyzed reductive coupling arena while providing an unconventional new platform for incorporating electrophilic sites at remote sp2 C-H linkages.

Cobalt Complexes as an Emerging Class of Catalysts for Homogeneous Hydrogenations.

Catalytic hydrogenation using molecular hydrogen represents a green and practical approach for reductions of all kinds of organic chemicals. Traditionally, in the majority of these processes the presence of transition metal catalysts is required. In this regard, noble-metal-based catalysts have largely been implemented, such as the application of iridium, palladium, rhodium, ruthenium, and others. Recently, the employment of earth-abundant 3d metals has emerged to replace the utilization of scarce noble metals because of their availability, lower cost, and often reduced toxicity. In this respect, several cobalt complexes, in the form of either molecularly well-defined or in situ-formed complexes, are receiving increasing attention from the scientific community. Importantly, the stability and reactivity of the complexes have greatly been supported by multidentate ligands under steric and/or electronic influences. For instance, tridentate or tetradentate phosphine ligands indirectly tune the reactivity of the metal center to accelerate the overall process, whereas direct participation of the ligand in pincer-type complexes through ligand-metal cooperation regulates the elementary steps in the catalytic cycle. In this Account, we emphasize specifically the advancements in cobalt-catalyzed hydrogenations using molecular hydrogen accomplished in our group. A variety of substrate classes ranging from simple molecules (e.g., carbon dioxide) to complex compounds were explored under the mild and efficient catalytic conditions. Notable examples include the reduction of carbon dioxide to afford either formates using a Co(BF4)2·6H2O/Tetraphos catalyst system or methanol employing a Co(acac)3/Triphos complex in the presence of HNTf2. As interesting examples of the synthesis of fine chemicals, cobalt-promoted hydrogenations of nitriles to primary amines and reductive alkylations of indoles using carboxylic acids as alkylating agents are highlighted. Moreover, highly selective hydrogenations of N-heteroarenes under additive-free conditions were possible by the application of specific cobalt complexes. More recently, a set of carboxylic esters could be hydrogenated to the corresponding alcohols with high efficiency by the use of a well-defined cobalt-PNP pincer catalyst. In particular, the decent reactivity of cobalt catalysts enabled high selectivity and functional group tolerance to be achieved. Throughout our studies, it was found that the pairing of a suitable cobalt precursor and an appropriate tridentate or tetradentate phosphine ligand plays a crucial role harnessing the desired reactivity, while other monodentate and bidentate phosphine ligands showed no reactivity in these investigations. Our developments could provide supervisory information for the future exploration of cobalt-catalyzed hydrogenation reactions and other types of reactions involving cobalt catalysis. Furthermore, relevant contributions from other groups, remaining challenges, and future perspectives in this research area are also presented.

Site-Selective, Remote sp3 C-H Carboxylation Enabled by the Merger of Photoredox and Nickel Catalysis.

A photoinduced carboxylation of alkyl halides with CO2 at remote sp3 C-H sites enabled by the merger of photoredox and Ni catalysis is described. This protocol features a predictable reactivity and site selectivity that can be modulated by the ligand backbone. Preliminary studies reinforce a rationale based on a dynamic displacement of the catalyst throughout the alkyl side chain.

A Radical Revolution for Trifluoromethoxylation.

The study of OCF3 -substituted molecules is somewhat hampered by a lack of diverse synthetic methods to access them. By introducing a new mild and practical reaction system for accessing the . OCF3 radical, a recent study by Liu, Ngai, and co-workers has the potential to dramatically expand the scope of direct trifluoromethoxylation. The features of this ground-breaking system are discussed and placed into context with other recent advances on nucleophilic trifluoromethoxylation.

Tailored Cobalt-Catalysts for Reductive Alkylation of Anilines with Carboxylic Acids under Mild Conditions.

The first cobalt-catalyzed hydrogenative N-methylation and alkylation of amines with readily available carboxylic acid feedstocks as alkylating agents and H2 as ideal reductant is described. Combination of tailor-made triphos ligands with cobalt(II) tetrafluoroborate significantly improved the efficiency, thus promoting the reaction under milder conditions. This novel protocol allows for a broad substrate scope with good functional group tolerance, even in the presence of reducible alkenes, esters, and amides.

Hydrogenation of Pyridines Using a Nitrogen-Modified Titania-Supported Cobalt Catalyst.

Novel heterogeneous catalysts were prepared by impregnation of titania with a solution of cobalt acetate/melamine and subsequent pyrolysis. The resulting materials show an unusual nitrogen-modified titanium structure through partial implementation of nitrogen into the support. The optimal catalyst displayed good activity and selectivity for challenging pyridine hydrogenation under acid free conditions in water as solvent.

A Biomass-Derived Non-Noble Cobalt Catalyst for Selective Hydrodehalogenation of Alkyl and (Hetero)Aryl Halides.

Hydrodehalogenation is a straightforward approach for detoxifications of harmful anthropogenic organohalide-based pollutants, as well as removal of halide protecting groups used in multistep syntheses. A novel sustainable catalytic material was prepared from biowaste (chitosan) in combination with an earth-abundant cobalt salt. The heterogeneous catalyst was fully characterized by transmission electron microscope, X-ray diffraction, and X-ray photoelectron spectroscopy measurements, and successfully applied to hydrodehalogenation of alkyl and (hetero)aryl halides with broad scope (>40 examples) and excellent chemoselectivity using molecular hydrogen as a reductant. The general usefulness of this method is demonstrated by successful detoxification of non-degradable pesticides and fire retardants. Moreover, the potential of the catalyst as a deprotection tool is demonstrated in a multistep synthesis of (±)-peronatin B (alkaloid).

Accelerated Discovery in Photocatalysis using a Mechanism-Based Screening Method.

Herein, we report a conceptually novel mechanism-based screening approach to accelerate discovery in photocatalysis. In contrast to most screening methods, which consider reactions as discrete entities, this approach instead focuses on a single constituent mechanistic step of a catalytic reaction. Using luminescence spectroscopy to investigate the key quenching step in photocatalytic reactions, an initial screen of 100 compounds led to the discovery of two promising substrate classes. Moreover, a second, more focused screen provided mechanistic insights useful in developing proof-of-concept reactions. Overall, this fast and straightforward approach both facilitated the discovery and aided the development of new light-promoted reactions and suggests that mechanism-based screening strategies could become useful tools in the hunt for new reactivity.

External-Photocatalyst-Free Visible-Light-Mediated Synthesis of Indolizines.

A visible-light-mediated synthesis of valuable polycyclic indolizine heterocycles from easily accessed brominated pyridine and enol carbamate derivatives has been developed. This process, which operates at room temperature under irradiation from readily available light sources, does not require the addition of an external photocatalyst. Instead, an investigation into the reaction mechanism indicates that the indolizine products themselves may be in some way involved in mediating and accelerating their own formation. Preliminary studies also show that these simple heterocyclic compounds may be capable of facilitating other visible-light-mediated transformations.

Visible-Light Photoredox-Catalyzed Semipinacol-Type Rearrangement: Trifluoromethylation/Ring Expansion by a Radical-Polar Mechanism.

A visible-light-mediated photoredox-catalyzed semipinacol-type rearrangement proceeding via 1,2 alkyl migration was developed. In this transformation, trifluoromethylation of the C=C bond of α-(1-hydroxycycloalkyl)-substituted styrene derivatives is followed by ring expansion of the 1-hydroxycycloalkyl group to deliver novel cycloalkanones with all-carbon quaternary centers. The reaction proceeds via a radical-polar mechanism, with trifluoromethylation (radical) and ring expansion (ionic) occurring in the same transformation.

N-heterocyclic carbene catalyzed switchable reactions of enals with azoalkenes: formal [4 + 3] and [4 + 1] annulations for the synthesis of 1,2-diazepines and pyrazoles.

A regio- and enantioselective formal [4 + 3] annulation reaction between enals and in situ formed azoalkenes has been achieved. A diverse set of 1,2-diazepine derivatives were synthesized in good yields with excellent enantioselectivities (often 99% ee). Alternatively, modifying the standard NHC catalyst switched the reactivity toward a formal [4 + 1] annulation to afford functionalized pyrazoles. The electronic and steric properties of the N-heterocyclic carbene organocatalyst play a vital role in controlling the reaction pathway (homoenolate vs acyl-anion reactivity of enal), allowing selective access to diverse 1,2-diazepine and pyrazole derivatives from identical substrates.

Dual catalysis sees the light: combining photoredox with organo-, acid, and transition-metal catalysis.

The photoredox activation of organic substrates with visible light is a powerful methodology that generates reactive radical species under very mild conditions. When combined with another catalytic process in a dual catalytic system, novel, visible-light-promoted transformations have been realized that do not proceed using either catalyst in isolation. In this minireview, the state of the art in organic reactions mediated by dual catalytic systems merging photoredox activation with organo-, acid or metal catalysis is discussed.

Conjugate umpolung of ß,ß-disubstituted enals by dual catalysis with an N-heterocyclic carbene and a Brønsted acid: facile construction of contiguous quaternary stereocenters.

A sterically hindered homoenolate has been generated by the NHC-catalyzed conjugate umpolung of ß,ß-disubstituted enals and successfully employed in a facile stereoselective annulation with isatins. The strategy provides efficient access to spirocyclic oxindoles bearing two highly congested contiguous quaternary carbon centers. The use of a Brønsted acid cocatalyst was found to be crucial for guaranteeing both excellent reactivity and high stereoselectivity.

Unifying N-Sulfinylamines with Alkyltrifluoroborates by Organophotoredox Catalysis: Access to Functionalized Alkylsulfinamides and High-Valent S(VI) Analogues.

We describe an organophotoredox-catalyzed sp3 C-S coupling of N-sulfinylamines with bench-stable alkyltrifluoroborates as a latent nucleophilic counterpart en route to alkylsulfinamides in high efficiency. In contrast to the two-electron reactivity of traditional organometallic reagents, this catalytic method reports the single-electron process of an organometallic reagent with N-sulfinylamines in C-S coupling. This mild and scalable protocol offers operational simplicity and exceptional functional group compatibility, including ketone, ester, amide, nitrile, and halides, that is vulnerable to organolithium or Grignard reagents. Additionally, the sulfinamides are conveniently converted to a variety of important S(VI) compounds, like sulfonamides, sulfonimidamides, and sulfonimidates, among others.

Regioselective 1,2-Alkylboration of Benzylidenecyclopropanes: Access to Csp3-Enriched Cyclopropyl Boronic Esters.

We describe a novel, regioselective alkylboration of versatile (hetero)benzylidenecyclopropanes with ß-H-containing alkyl iodides and bis(pinacolato)diboron enabled by copper catalysis. This three-component method allows for consecutive B-Csp3 and Csp3-Csp3 bond formation to access Csp3-enriched diverse tertiary cyclopropyl boronic esters with broad functionality tolerance, and the so-formed C-B bond is amenable to further structural diversification. Radical clock experiment, Hammett analysis, and DFT calculation suggest a mechanism of polar, rather than radical manifold, and SN2-type C-C bond formation was found to be the rate-limiting step instead of migratory alkene insertion.