Modifying Proton Relay into Bioinspired Dye-based Coordination Polymer for Photocatalytic Proton-Coupled Electron Transfer.

Proton-coupled electron transfer (PCET) imparts an energetic advantage over solo electron transfer in activating inert substances. Natural PCET enzyme catalysis generally requires tripartite preorganization of proton relay, substrate-bound active center, and redox mediator, making the processes efficient and precluding side reactions. Inspired by this, a heterogeneous photocatalytic PCET system was established to achieve higher PCET driving forces by modifying proton relays into anthraquinone-based anionic coordination polymers. The proximally separated proton relays and photoredox-mediating anthraquinone moiety allowed pre-assembly of inert substrate between them, merging proton and electron into unsaturated bond by photoreductive PCET, which enhanced reaction kinetics than the counter catalyst without proton relay. This photocatalytic PCET method was applied to a broad-scoped reduction of aryl ketones, unsaturated carbonyls, and aromatic compounds. The distinctive regioselectivities for the reduction of isoquinoline derivatives were found to occur on the carbon-ring sides. PCET-hydrogenated radical intermediate of quinoline could be trapped by alkene for proton relay-assisted Minisci addition, forming the pharmaceutical aza-acenaphthene scaffold within one step. When using heteroatom(X)-H/C-H compounds as proton-electron donors, this protocol could activate these inert bonds through photooxidative PCET to afford radicals and trap them by electron-deficient unsaturated compounds, furnishing the direct X-H/C-H functionalization.

Harnessing Radicals in Confined Supramolecular Environments Made Possible by MOFs.

Researching and utilizing radical intermediates in organic synthetic chemistry have innovated discoveries in methodology and theory. Reactions concerning free radical species opened new pathways beyond the frame of the two-electron mechanism while commonly characterized as rampant processes lacking selectivity. As a result, research in this field has always focused on the controllable generation of radical species and determining factors of selectivity. Metal-organic frameworks (MOFs) have emerged as compelling candidates as catalysts in radical chemistry. From a catalytic point of view, the porous nature of MOFs entails an inner phase for the reaction that could offer possibilities for the regulation of reactivity and selectivity. From a material science perspecti ve, MOFs are organic-inorganic hybrid materials that integrate functional units in organic compounds and complex forms in the tunable long-ranged periodic structure. In this account, we summarized our progress in the application of MOFs in radical chemistry in three parts: (1) The generation of radical species; (2) The weak interactions and site selectivity; (3) Regio- and stereo-selectivity. The unique role of MOFs play in these paradigms is demonstrated in a supramolecular narrative through the analyses of the multi-constituent collaboration within the MOF and the interactions between MOFs and the intermediates during the reactions.

Visible-light-mediated α-amino alkylation of ketimines and aldimines for the synthesis of 1,2-diamines.

A visible-light-mediated protocol to prepare 1,2-diamines has been successfully explored based on the photoredox/Brønsted acid co-catalyzed α-amino alkylations of imines with tertiary amines. Both ketimines and aldimines are applicable to this transformation. Various 1,2-diamines with different functional groups were produced in moderate to excellent yields. Moreover, this approach could be performed on a gram scale, showing its practicality.

A Diode-Like Dye-Cu Anisotropic Junction in a Coordination Polymer as a Logic State Ratchet for Intratumor Redox Photomodulation.

Redox logic materials offer new avenues to modulate intracellular pathologic redox environment area-specifically, but the unambiguity of redox logic states and their unidirectional and repetitive switchability are challenging to realize. By merging a bistable diisophthalic phenazine dye ligand with CuII salt, a multistable coordination polymer (CP) was constructed, of which the dye-Cu anisotropic junction achieved the diode-like unidirectional electron transfer and logic state ratchet for the first time. Radical cationic CP maintained OFF status with low toxicity in healthy tissues, but was reduced to the neutral SERVO state by the overexpressed glutathione (GSH) in hypoxic tumors. After photoirradiation, the stabilized charge-separated ON status promoted photo-Fenton reaction for reactive oxygen species (ROS) signal transduction, and simultaneously recovered the initial state for catalytic signal amplification of ROS, furnishing intratumor redox photomodulation for therapy.

Direct Utilization of Near-Infrared Light for Photooxidation with a Metal-Free Photocatalyst.

Near-infrared (NIR) light-triggered photoredox catalysis is highly desirable because NIR light occupies almost 50% of solar energy and possesses excellent penetrating power in various media. Herein we utilize a metal-free boron dipyrromethene (BODIPY) derivative as the photocatalyst to achieve NIR light (720 nm LED)-driven oxidation of benzylamine derivatives, sulfides, and aryl boronic acids. Compared to blue light-driven photooxidation using Ru(bpy)3Cl2 as a photocatalyst, NIR light-driven photooxidation exhibited solvent independence and superior performance in large-volume (20 mL) reaction, presumably thanks to the neutral structure of a BODIPY photocatalyst and the deeper penetration depth of NIR light. We further demonstrate the application of this metal-free NIR photooxidation to prodrug activation and combination with Cu-catalysis for cross coupling reaction, exhibiting the potential of metal-free NIR photooxidation as a toolbox for organic synthesis and drug development.

Rhodium-Catalyzed Highly Regioselective and Stereoselective Intermolecular Hydrosilylation of Internal Ynamides under Mild Conditions.

A rhodium-catalyzed highly regio- and stereoselective intermolecular hydrosilylation of internal ynamides has been developed. With the neutral rhodium complex [Rh(CO)2Cl]2 as a catalyst and the bulky silanes as reactants, various ynamides underwent hydrosilylation smoothly at room temperature with an excellent ß-regioselectivity and anti-stereoselectivity. The synthetically versatile ß-silyl ( Z)-enamide products could be further transformed to diverse useful building blocks. Several possible mechanisms are proposed to rationalize this unique formal trans-addition-type selectivity.

Copper-catalyzed synthesis of indolyl diketones via C-H oxidation/diacylation of indoles with arylglyoxal hydrates.

An expedient protocol for Cu-catalyzed C-H oxidation/diacylation of indoles with arylglyoxal hydrates to construct indolyl diketones is developed. This methodology exhibits the synthetic utility of the synthesis of an indole-alkaloid 1,2-di(1H-indol-3-yl)ethane-1,2-dione and offers a straightforward means to produce different indolyl nitrogen-containing heterocycles such as indolyl quinoxaline, indolyl hydantoin and indolyl imidazole in high yields. Preliminary mechanistic studies indicate that two proposed pathways are involved in this process.

Metal-free C-H bond activation of branched aldehydes with a hypervalent iodine(III) catalyst under visible-light photolysis: successful trapping with electron-deficient olefins.

Direct acyl radical formation of linear aldehydes (RCH2-CHO) and subsequent hydroacylation with electron-deficient olefins can be effected with various types of metal and nonmetal catalysts/reagents. In marked contrast, however, no successful reports on the use of branched aldehydes have been made thus far because of their strong tendency of generating alkyl radicals through the facile decarbonylation of acyl radicals. Here, use of a hypervalent iodine(III) catalyst under visible light photolysis allows a mild way of generating acyl radicals from various branched aldehydes, thereby giving the corresponding hydroacylated products almost exclusively. Another characteristic feature of this approach is the catalytic use of hypervalent iodine(III) reagent, which is a rare example on the generation of radicals in hypervalent iodine chemistry.

Confinement Effect in Metal-Organic Framework Cu3(BTC)2 for Enhancing Shape Selectivity of Radical Difunctionalization of Alkenes.

The radical difunctionalization of alkenes plays a vital role in pharmacy, but the conventional homogeneous catalytic systems are challenging in selectivity and sustainability to afford the target molecules. Herein, the famous readily available metal-organic framework (MOF), Cu3(BTC)2, has been applied to cyano-trifluoromethylation of alkenes as a high-performance and recyclable heterogeneous catalyst, which possesses copper(II) active sites residing in funnel-like cavities. Under mild conditions, styrene derivatives and various unactivated olefins could be smoothly transformed into the corresponding cyano-trifluoromethylation products. Moreover, the transformation brought about by the active copper center in confined environments achieved regio- and shape selectivity. To understand the enhanced selectivity, the activation manner of the MOF catalyst was studied with control catalytic experiments such as FT-IR and UV-vis absorption spectroscopy of substrate-incorporated Cu3(BTC)2, which elucidated that the catalyst underwent a radical transformation with the intermediates confined in the MOF cavity, and the confinement effect endowed the method with pronounced selectivities.

Chalcogen-bridged coordination polymer for the photocatalytic activation of aryl halides.

The ability to deliver electrons is vital for dye-based photocatalysts. Conventionally, the aromatic stacking-based charge-transfer complex increases photogenerated electron accessibility but decreases the energy of excited-state dyes. To circumvent this dilemma, here we show a strategy by tuning the stacking mode of dyes. By decorating naphthalene diimide with S-bearing branches, the S···S contact-linked naphthalene diimide string is created in coordination polymer, thereby enhancing electron mobility while simultaneously preserving competent excited-state reducing power. This benefit, along with in situ assembly between naphthalene diimide strings and exogenous reagent/reactant, improves the accessibility of short-lived excited states during consecutive photon excitation, resulting in greater efficiency in photoinduced electron-transfer activation of inert bonds in comparison to other coordination polymers with different dye-stacking modes. This heterogeneous approach is successfully applied in the photoreduction of inert aryl halides and the successive formation of CAr-C/S/P/B bonds with potential pharmaceutical applications.

Dye-polyoxometalate coordination polymer as a photo-driven electron pump for photocatalytic radical coupling reactions.

To alleviate diffusion-limited photoinduced electron transfer (PET) in solution, a triphenylamine-derived dye and a Keggin polyoxometalate-type electron relay were coupled into a coordination polymer to photoinduce long-lived charge-separation pairs with enough reductive/oxidative potential to pump multiple electrons unidirectionally from external electron donors to acceptors, thus furnishing photocatalytic radical couplings to afford value-added α-amino C-H arylation products.

Cascade nucleophilic addition-cyclic Michael addition of arynes and phenols/anilines bearing ortho alpha,beta-unsaturated groups: facile synthesis of 9-functionalized xanthenes/acridines.

A facile synthesis of xanthenes and acridines based on a cascade nucleophilic addition-cyclic Michael addition process of arynes and phenols/anilines substituted with alpha,beta-unsaturated groups at the ortho positions is described. The reaction has also been successfully extended to the synthesis of 9-spiro-xanthene and acridine derivatives with potential biochemical interest.

Synergistic photoredox and copper catalysis by diode-like coordination polymer with twisted and polar copper-dye conjugation.

Synergistic photoredox and copper catalysis confers new synthetic possibilities in the pharmaceutical field, but is seriously affected by the consumptive fluorescence quenching of Cu(II). By decorating bulky auxiliaries into a photoreductive triphenylamine-based ligand to twist the conjugation between the triphenylamine-based ligand and the polar Cu(II)-carboxylate node in the coordination polymer, we report a heterogeneous approach to directly confront this inherent problem. The twisted and polar Cu(II)-dye conjunction endows the coordination polymer with diode-like photoelectronic behaviours, which hampers the inter- and intramolecular photoinduced electron transfer from the triphenylamine-moiety to the Cu(II) site and permits reversed-directional ground-state electronic conductivity, rectifying the productive loop circuit for synergising photoredox and copper catalysis in pharmaceutically valuable decarboxylative C(sp3)-heteroatom couplings. The well-retained Cu(II) sites during photoirradiation exhibit unique inner-spheric modulation effects, which endow the couplings with adaptability to different types of nucleophiles and radical precursors under concise reaction conditions, and distinguish the multi-olefinic moieties of biointeresting steride derivatives in their late-stage trifluoromethylation-chloration difunctionalisation.

Dye-incorporated coordination polymers for direct photocatalytic trifluoromethylation of aromatics at metabolically susceptible positions.

Direct trifluoromethylation of unactivated aromatic rings at metabolically susceptible positions is highly desirable in pharmaceutical applications. By incorporating thiophenes into the backbone of triphenylamine to enlarge its π-system, a new approach for constructing coordination polymers is reported for direct trifluoromethylation without prefunctionalization of the aryl precursors. The improved light-harvesting ability and well-modulated excited state redox potential of the designed polymers endow the generated CF3 radicals with suitable reactivity and enhance radical adduct oxidation in pores. The well-configurated interactions between the organic ligands distort the coordination geometry to create active interaction sites within the coordination polymer; thus, the substrates could be docked near the photoredox-active centres. The synergistic electronic and spatial effects in the confined pores balance the contradictory demands of electronic effects and reaction dynamics, achieving regio- and diastereoselective discrimination among reaction sites with unremarkable electronic/steric differences.

Pyrene-based metal-organic framework NU-1000 photocatalysed atom-transfer radical addition for iodoperfluoroalkylation and (Z)-selective perfluoroalkylation of olefins by visible-light irradiation.

The photocatalytic atom-transfer radical addition (ATRA) of perfluoroalkyl iodides onto olefins is of potential biointerest; the relatively negative reductive potential of perfluoroalkyl iodide makes it difficult to generate the perfluoroalkyl radical by the photoinduced single-electron transfer from the excited state of the photocatalyst. In the presence of the easily available well-known pyrene-based metal-organic framework (MOF) NU-1000, the ATRA was achieved for iodoperfluooralkylation of olefins in a heterogeneous mode upon 405 nm visible-light irradiation with LEDs. The investigation supports a mechanism whereby the pyrene-based chromophores within NU-1000 photochemically generate the reactive radical species by sensitisation of the perfluoroalkyl iodides through an energy-transfer (EnT) pathway. Besides the activation of singlet oxygen for oxidative application, it is the first time to directly utilise the photoinduced EnT process of MOFs in organic transformations. Compared with the photocatalysis using homogeneous free ligand or other pyrene-based MOFs, the spatial isolation of chromophores in NU-1000 is believed to hamper the destructive excited-state energy loss from self-quenching or interligand interactions, ensuring the efficiency of reaction. When employing conjugated arylalkenes as substrates, the photocatalytic ATRA reaction, the HI elimination of the ATRA product, and the EnT-mediated (E)/(Z)-isomerisation could be merged together in one-pot to afford highly (Z)-selective perfluoroalkyl styrenes, which might be attractive in the pharmaceutical field.

Reaction of allenyl esters with sodium azide: an efficient synthesis of e-vinyl azides and polysubstituted pyrroles.

The nucleophilic addition of sodium azide to 1,2-allenyl esters can generate vinyl azides in excellent yields with excellent regio- and stereoselectivities. Moreover, pyrroles are synthesized using 1-allyllic 1,2-allenyl esters as substrates in t-BuOH at 65 degrees C. The sequential reaction for pyrroles is developed on the basis of a novel domino process involving nucleophilic addition, cycloaddition, denitrogenation, and aromatization.