Bridging the incompatibility gap in dual asymmetric catalysis over a thermoresponsive hydrogel-supported catalyst.

The integration of dual asymmetric catalysis is highly beneficial for the synthesis of organic molecules with multiple stereocenters. However, two major issues that need to be addressed are the intrinsic deactivation of dual-species and the extrinsic conflict of reaction conditions. To overcome these concerns, we have utilized the compartmental and thermoresponsive properties of poly(N-isopropylacrylamide) (PNIPAM) to develop a cross-linked PNIPAM-hydrogel-supported bifunctional catalyst. This catalyst is designed with Rh(diene) species situated on the outer surface and Ru(diamine) species positioned within the interior of the hydrogel. The compartmental function of PNIPAM in the middle overcomes intrinsic mutual deactivations between the dual-species. The thermoresponsive nature of PNIPAM allows for precise control of catalytic pathways in resolving external conflicts by controlling the reaction switching between an Rh-catalyzed enantioselective 1,4-addition at 50°C and a Ru-catalyzed asymmetric transfer hydrogenation (ATH) at 25°C. As we envisioned, this sequential 1,4-addition/reduction dual enantioselective cascade reaction achieves a transformation from incompatibility to compatibility, resulting in direct access to γ-substituted cyclic alcohols with dual stereocenters in high yields and enantio/diastereoselectivities. Mechanistic investigation reveals a reversible temperature transition between 50°C and 25°C, ensuring a cascade process comprising a 1,4-addition followed by the ATH process.

BODIPY Based OFF-ON Fluorescent Probe for Endogenous Carbon Monoxide Imaging in Living Cells.

Carbon monoxide (CO) is one of the signaling molecules that are ubiquitous in humans, which involves in the regulation of human physiology and pathology. In this work, the probe PEC was designed and synthesized based on BODIPY fluorophore that can selectively detect CO through reducing the nitro group to amino group, resulting in a "turn-on" fluorescence response with a simultaneous increase in the concentration of CO. The response is selective over a variety of relevant reactive free radicals, ions, and amino acid species. PEC has the advantages of good stability, good water solubility, and obvious changes in fluorescence signals. In addition, PEC can be used to detect and track endogenous CO in living cells.

Pyridinium-Masked Enol as a Precursor for Constructing Alpha-Fluoromethyl Ketones.

We present herein a pyridinium-masked enol as a versatile platform to produce ketones bearing tri-, di-, and monofluoromethyl in the presence of [Ir(dF(Me)ppy)]2(dtbbpy)]PF6 under blue light (455 nm) irradiation. By simply changing the F-source, α-trifluoromethyl ketones, α-difluoromethyl ketones, and α-monofluoromethyl ketones could be easily prepared in moderate to excellent yields in one step, making it a practical tool for the synthesis of fluorine-containing ketones. In addition, the pyridinium-masked enol could also be extended to the synthesis of sulfonyl ketones. The findings of the present protocol contribute to the arsenal of fluorine chemistry and might have potential applications in the pharmaceutical and agrochemical industries.

Integrated Suzuki Cross-Coupling/Reduction Cascade Reaction of meta-/para-Chloroacetophenones and Arylboronic Acids under Batch and Continuous Flow Conditions.

Overcoming the incompatibility of a pair of conflicting catalysts via a flow methodology has great significance in the practical applications for multistep organic transformations. In this study, a multiple continuous-flow system is developed, which can boost the reactivity and selectivity in a sequential enantioselective cascade reaction. During this process, a periodic mesoporous organosilica-supported Pd/carbene species as a Suzuki cross-coupling catalyst is packed in the first column reactor, whereas another periodic mesoporous organosilica-supported Ru/diamine species as an asymmetric transfer hydrogenation catalyst is packed in the second column reactor. As we envisioned, the initially Pd-catalyzed cross-coupling reaction of meta-/para-chloroacetophenones and aryl boronic acids followed by the subsequentially Ru-catalyzed reduction provides chiral biarylols with enhanced yields and enantioselectivities. Furthermore, the advantages of the easy handling and the simple procedure make this system an attractive application in a scale-up preparation of optically pure organic molecules under environmentally-friendly conditions.

Mechanistic Insights into the Ru(II)-Catalyzed Intramolecular Formal [3 + 2] Cycloaddition of (E)-1,6-Enynes.

Design of a unique reaction pathway in transition-metal-catalyzed 1,6-enynes cyclization to construct valuable synthetic motifs is a significant challenge in organic chemistry. Herein, we report a Ru(II)-catalyzed formal [3 + 2] cycloaddition as an efficient method to prepare unprecedented bicyclo[3.3.0]octenes from readily available (E)-1,6-enynes. Mechanistic studies based on the deuterium labeling experiments and the DFT calculation disclose a reasonable mechanistic pathway, where a ruthenacyclopentene generated by an ene-yne oxidative cyclization undergoes a sequential ß-hydride elimination and intramolecular hydroruthenation to form a ruthenacyclohexene, producing the desirable bicyclo[3.3.0]octenes.

An integrated immobilization strategy manipulates dual active centers to boost enantioselective tandem reactions.

Manipulation of dual active centers via an integrated immobilization strategy can overcome the restriction of homogeneous catalysis in a sequential organic transformation. Herein, by utilizing hollow-shell-structured silica, hydrogen-bonding immobilization via a ship-in-a-bottle synthesis locks a Pd(carbene) center in a nanocage and covalent-bonding immobilization tethers chiral Ru(diamine) centers within the nanochannels, constructing a hetero-bifunctional catalyst. The benefit of this dual center manipulation enables a challenging Suzuki coupling-asymmetric transfer hydrogenation tandem reaction, and the advantage of this process provides various chiral biarylols with enhanced reactivity and enantioselectivity.

A nitroreductase and acidity detecting dual functional ratiometric fluorescent probe for selectively imaging tumor cells.

Nitroreductase and acidity are common features of a tumor, which is associated with serious disease with a high mortality rate. However, solo detection of nitroreductase or acidic environments may cause false-positive results. Thus, it is very meaningful to develop dual functional probes for detecting nitroreductase and acidity, as these could be used for accurate tumor imaging. Here we report on the first dual functional ratiometric fluorescent probe, NAFP, for acidity and nitroreductase detection. This probe enables the measurement of the acidic microenvironment and the concentration of nitroreductase at the same time and the same site. The probe can obviously distinguish acidity, nitroreductase, and nitroreductase in an acidic environment. Furthermore, confocal fluorescence imaging of A549 cells indicates that NAFP can detect acidity and expressed nitroreductase in living cells.

A Michael Addition-Asymmetric Transfer Hydrogenation One-Pot Enantioselective Tandem Process for Syntheses of Chiral γ-Secondary Amino Alcohols.

An aza-Michael addition-asymmetric transfer hydrogenation tandem process for preparation of chiral γ-secondary amino alcohols has been developed. This one-pot tandem process involves an aza-Michael addition of aryl-substituted enones and amines to form aryl-substituted γ-secondary amino ketones, followed by a Ru-catalyzed asymmetric transfer hydrogenation to form aryl-substituted γ-secondary amino alcohols. An advantageous feature of this tandem reaction is that it provides various γ-secondary amino alcohols in high yields with high enantioselectivities.

A dynamic kinetic asymmetric transfer hydrogenation-cyclization tandem reaction: an easy access to chiral 3,4-dihydro-2H-pyran-carbonitriles.

A chiral (mesitylene)RuCl(monosulfonated diamine) catalysed dynamic kinetic resolution (DKR)-asymmetric transfer hydrogenation (ATH) process is developed for highly enantio- (up to 99% ee) and diastereo- (up to 98 : 2 dr) selective reduction of challenging racemic α-aryl-γ-keto malononitriles. A spontaneous cyclization reaction of the hydrogenation products delivers a cascade process for efficient synthesis of useful enantioenriched 3,4-dihydro-2H-pyran-carbonitriles.

AND logic-like pH- and light-dual controlled drug delivery by surface modified mesoporous silica nanoparticles.

Recently, the controlled drug delivery system has become a potential platform for biomedical application. Herein, we developed a pH and light-dual controlled cargo release system exhibiting AND logic based on MCM-41 mesoporous silica nanoparticles, which was surface modified using ß-cyclodextrin (ß-CD) with imine bond and azobenzene derivative. The complex of ß-CD and azobenzene derivative effectively blocked the cargo delivery in pH=7.0 phosphate buffered saline (PBS) solution without 365nm UV light irradiation. The cargo was fully released when both factors of acidic environment (pH=5.0 PBS) and 365nm UV light irradiation were satisfied, meanwhile only very little cargo was delivered if one factor was satisfied. The result also demonstrates that the opening/closing of the gate and the release of the cargo in small portions can be controlled.

Integration of multiple active sites on large-pore mesoporous silica for enantioselective tandem reactions.

Facile construction of a multifunctional heterogeneous catalyst through the assembly of Au/carbene and chiral ruthenium/diamine dual complexes in large-pore mesoporous silica was developed. This enables an efficient one-pot hydration-asymmetric transfer hydrogenation enantioselective tandem reaction of haloalkynes, affording chiral halohydrins with up to 99% enantioselectivity. Combined multifunctionalities, such as substrate-promoted silanol-functionality, BF4- anion-bonding gold/carbene and covalent-bonding chiral ruthenium/diamine active centers, contributed cooperatively to the catalytic performance.

A Cinchona Alkaloid-Functionalized Mesostructured Silica for Construction of Enriched Chiral ß-Trifluoromethyl-ß-Hydroxy Ketones over An Epoxidation-Relay Reduction Process.

A cinchona alkaloid-functionalized heterogeneous catalyst is prepared through a thiol-ene click reaction of chiral N-(3,5-ditrifluoromethylbenzyl)quininium bromide and a mesostructured silica, which is obtained by co-condensation of 1,2-bis(triethoxysilyl)ethane and 3-(triethoxysilyl)propane-1-thiol. Structural analyses and characterizations disclose its well-defined chiral single-site active center, and electron microscopy images reveal its monodisperse property. As a heterogenous catalyst, it enables an efficient asymmetric epoxidation of achiral ß-trifluoromethyl-ß,ß-disubstituted enones, the obtained chiral products can then be converted easily into enriched chiral ß-trifluoromethyl-ß-hydroxy ketones through a sequential epoxidation-relay reduction process. Furthermore, such a heterogeneous catalyst can be recovered conveniently and reused in asymmetric epoxidation of 4,4,4-trifluoro-1,3-diphenylbut-2-enone, showing an attractive feature in a practical construction of enriched chiral ß-CF3 -substituted molecules.

Enantioselective tandem reaction over a site-isolated bifunctional catalyst.

Construction of a site-isolated heterogeneous catalyst to realize the compatibility of bimetallic complexes for a feasible tandem reaction is a significant challenge in heterogeneous asymmetric catalysis. Herein, taking advantage of yolk-shell-structured mesoporous silica, we assemble an active site-isolated bifunctional catalyst through assembly of organopalladium-functionality into silicate channels as an outer shell and chiral organoruthenium-functionality onto silicate yolk as an inner core, realizing the one-pot enantioselective tandem reaction from Pd-catalyzed Sonogashira coupling to Ru-catalyzed asymmetric transfer hydrogenation. As presented in this study, this tandem Sonogashira coupling-asymmetric transfer hydrogenation of haloacetophenones and arylacetylenes affords various chiral conjugated alkynols with high yields and up to 99% enantioselectivity. Moreover, a catalyst can also be recovered easily and recycled repeatedly, making it an interesting feature in a practical organic transformation.

Dynamic Kinetic Resolution of Phthalides via Asymmetric Transfer Hydrogenation: A Strategy Constructs 1,3-Distereocentered 3-(2-Hydroxy-2-arylethyl)isobenzofuran-1(3H)-one.

Dynamic kinetic resolution of phthalides through asymmetric transfer hydrogenation for the construction of 3-(2-hydroxy-2-arylethyl)isobenzofuran-1(3H)-one with 1,3-distereocenters has been developed. This procedure is carried out under a mild condition at 40 °C catalyzed with RuCl[(S,S)-TsDPEN](mesitylene) using HCOOH/Et3N (5:2) as a hydrogen source. A variety of phthalides are smoothly transferred to provide optically pure phthalides with high yields, excellent enantioselectivities, and acceptable diastereomeric ratios.

Ru-Catalyzed asymmetric transfer hydrogenation of α-trifluoromethylimines.

Enantioselective transformation of strong electron-withdrawing acyclic α-trifluoromethylimines to α-trifluoromethylamines through a ruthenium-catalyzed asymmetric transfer hydrogenation has been developed. The method described here is a facile catalytic process with sodium formate as a hydrogen resource and water-dimethylformamide as a cosolvent. The benefit of this enantioselective transformation affords a series of chiral α-trifluoromethylamines with high yields and excellent enantioselectivities (93-99% ee) under mild reaction conditions.

Highly enantioselective one-pot synthesis of chiral ß-hydroxy sulfones via asymmetric transfer hydrogenation in an aqueous medium.

A mild transformation in an aqueous medium for the one-pot synthesis of optically active ß-hydroxy sulfones is described. The intermediates of ß-keto sulfones obtained via a nucleophilic substitution reaction of α-bromoketones and sodium sulfinates in H2O/MeOH (1:3, v/v) at 50 °C were reduced through Ru-catalyzed asymmetric transfer hydrogenation in one-pot using HCOONa as a hydrogen source providing a variety of chiral ß-hydroxy sulfones with high yields and excellent enantioselectivities.

Facile construction of functionalized periodic mesoporous organosilica for Ir-catalyzed enantioselective reduction of α-cyanoacetophenones and α-nitroacetophenones.

A facile method to construct chiral organoiridium-functionalized periodic mesoporous organosilica is developed. The heterogeneous catalyst displays excellent catalytic efficiency in the enantioselective reduction of α-cyanoacetophenones and α-nitroacetophenones in aqueous medium because of the hydrophobic nature and uniformly distributed active iridium species. The catalyst could be conveniently recovered and reused eight times without loss of its catalytic activity.

Enantio-relay catalysis constructs chiral biaryl alcohols over cascade Suzuki cross-coupling-asymmetric transfer hydrogenation.

The construction of chiral biaryl alcohols using enantio-relay catalysis is a particularly attractive synthetic method in organic synthesis. However, overcoming the intrinsic incompatibility of distinct organometallic complexes and the reaction conditions used are significant challenges in asymmetric catalysis. To overcome these barriers, we have taken advantage of an enantio-relay catalysis strategy and a combined dual-immobilization approach. We report the use of an imidazolium-based organopalladium-functionalized organic-inorganic hybrid silica and ethylene-coated chiral organoruthenium-functionalized magnetic nanoparticles to catalyze a cascade Suzuki cross-coupling-asymmetric transfer hydrogenation reaction to prepare chiral biaryl alcohols in a two-step, one-pot process. As expected, the site-isolated active species, salient imidazolium phase-transfer character and high ethylene-coated hydrophobicity can synergistically boost the catalytic performance. Furthermore, enantio-relay catalysis has the potential to efficiently prepare a variety of chiral biaryl alcohols. Our synthetic strategy is a general method that shows the potential of developing enantio-relay catalysis towards environmentally benign and sustainable organic synthesis.

Hollow-shell-structured nanospheres: a recoverable heterogeneous catalyst for rhodium-catalyzed tandem reduction/lactonization of ethyl 2-acylarylcarboxylates to chiral phthalides.

Chiral organorhodium-functionalized hollow-shell-structured nanospheres were prepared by immobilization of a chiral N-sulfonylated diamine-based organorhodium complex within an ethylene-bridged organosilicate shell. Structural analysis and characterization reveal its well-defined single-site rhodium active center, and transmission electron microscopy images reveal a uniform dispersion of hollow-shell-structured nanospheres. As a heterogenous catalyst, it exhibits excellent catalytic activity and enantioselectivity in synthesis of chiral phthalides by a tandem reduction/lactonization of ethyl 2-acylarylcarboxylates in aqueous medium. The high catalytic performance is attributed to the synergistic effect of the high hydrophobicity and the confined chiral organorhodium catalytic nature. The organorhodium-functionalized nanospheres could be conveniently recovered and reused at least 10 times without loss of catalytic activity. This feature makes it an attractive catalyst in environmentally friendly organic reactions. The results of this study offer a new approach to immobilize chiral organometal functionalities within the hollow-shell-structured nanospheres to prepare materials with high activity in heterogeneous asymmetric catalysis.

Phenylene-coated magnetic nanoparticles that boost aqueous asymmetric transfer hydrogenation reactions.

Phenylene-coated organorhodium-functionalized magnetic nanoparticles are developed through co-condensation of chiral 4-(trimethoxysilyl)ethyl)phenylsulfonyl-1,2-diphenylethylene-diamine and 1,4-bis(triethyoxysilyl)benzene onto Fe3O4 followed complexation with [{Cp*RhCl2}2]. This magnetic catalyst exhibits excellent catalytic activity and high enantioselectivity in asymmetric transfer hydrogenation in aqueous medium. Such activity is attributed to the high hydrophobicity and the confined nature of the chiral organorhodium catalyst. The magnetic catalyst can be easily recovered by using a small external magnet and it can be reused for at least 10 times without loss of its catalytic activity. This characteristic makes it an attractive catalyst for environmentally friendly organic syntheses.