Rapid Access to Chiral Spiro[2.3] Lactams: Stereoselective Hydroborylation and Hydrosilylation and Remote Control of Axial Chirality by Copper-Catalyzed Desymmetrization of Spirocyclopropenes.

Chiral spirocyclopropyl ß-lactams are common motifs in bioactive compounds and pharmaceuticals. Here we disclose a diastereoselective and enantioselective hydroborylation and hydrosilylation of spirocyclopropenes, via a Cu-catalyzed desymmetrization strategy, for the rapid preparation of enantio-enriched spirocyclopropyl ß-lactams. The efficient desymmetrization strategy allows the remote control of axial chirality, offering the borylated and silylated products bearing central, spiro, and axial chirality. The combination of multichiral elements would provide a novel motif for biological evaluation in potential drug discovery.

Transition-metal-free and additive-free intermolecular hydroarylation of alkenes with indoles in hexafluoroisopropanol.

Hydroarylation of alkenes is one of the most straightforward and atom-economical strategy for the construction of multi-aryl-substituted alkanes, but systematic studies have been limited to transition metal catalysis. Here we report a hexafluoroisopropanol (HFIP)-promoted hydroarylation of alkenes with indoles without the presence of transition metal catalysts or any additive. HFIP was the only reagent used in this work, and could be easily removed via evaporation, and recovered via distillation in industry settings. This reaction was shown to provide an efficient, clean and operationally simple procedure with a remarkable substrate scope and versatile transformations, delivering a variety of multi-aryl alkanes incorporating the indole motif. In preliminary studies, several of these products showed biologically activity against cells from an array of human cancer cell lines. A mechanistic study was also carried out and suggested that the quinone methide might be the key intermediate. And in contrast to the conclusions of a previous report, the current work suggested that protonation by HFIP might not be the rate-determining step.

Silver(I)-Catalyzed Diastereoselective Hydroborylation of Cyclopropenes.

An effective (NHC)AgCl catalysis was developed in the hydroborylation of cyclopropenes with B2pin2, delivering a variety of cyclopylboronates in a stereoselective manner, which could be easily transformed for the construction of versatile cyclopropanes. This protocol works effectively under mild reaction conditions in an open-air atmosphere, and it was easy to apply on a gram scale. This novel method in detail was also explored by control experiments, providing a number of key insights. The kinetic process followed by 1H NMR indicated that the reaction was finished in 15 min. Furthermore, the mechanism of silver(I)-catalyzed hydroborylation of cyclopropenes was proposed, with the protonation by methanol as the rate-determining step.

Nonbasic Synthesis of Thioethers via Nickel-Catalyzed Reductive Thiolation Utilizing NBS-Like N-Thioimides as Electrophilic Sulfur Donors.

The nonbasic synthesis of unsymmetrical thioethers via nickel-catalyzed reductive thiolation between aryl(hetero) iodides and N-thioimides is illustrated. N-Bromosuccinimide (NBS)-like N-thioimides were found quite reactive toward thiolation with carbon electrophiles, and a series of structurally varied thioethers were successfully prepared under mild reaction conditions. The transformation was featured with the new application of the NBS-like reagents, good functional group tolerance, and late-stage modification of biologically active scaffolds, thus providing an expeditious and efficient platform to construct polyfunctional thioethers.

Label-free fluorescence strategy for methyltransferase activity assay based on poly-thymine copper nanoclusters engineered by terminal deoxynucleotidyl transferase.

The assay of detecting DNA methyltransferase activity has been identified as one of the central challenges in cancer diagnostics as DNA methylation is closely related to the diagnosis and treatment of tumors. In this study, a label-free fluorescence probe based on poly-thymine copper nanoclusters engineered by terminal deoxynucleotidyl transferase is proposed for methyltransferase activity assay. Taking advantage of the efficient polymerization extension reaction catalyzed by terminal deoxynucleotidyl transferase and the copper nanoclusters with large Stokes shift instead of labeling fluorescent dyes, the strategy exhibits a broader linear scope from 1 to 300 U mL-1 with a detection limit of 0.176 U mL-1. The economical method is specificity for M.SssI and also provides a convenient and high-throughput platform for screening the DNA methylation inhibitors, which displays a great potential for the practical applications of the drug development and clinical cancer diagnosis in the future.

Catalytic Asymmetric trans-Selective Hydrosilylation of Bisalkynes to Access AIE and CPL-Active Silicon-Stereogenic Benzosiloles.

Chirality widely exists in a diverse array of biologically active molecules and life forms, and the catalytic constructions of chiral molecules have triggered a heightened interest in the fields of chemistry and materials and pharmaceutical sciences. However, the synthesis of silicon-stereogenic organosilicon compounds is generally recognized as a much more difficult task than that of carbon-stereogenic centers because of no abundant organosilicon-based chiral sources in nature. Herein, we reported a highly enantioselective rhodium-catalyzed trans-selective hydrosilylation of silicon-tethered bisalkynes to access chiral benzosiloles bearing a silicon-stereogenic center. This protocol featured with chiral Ar-BINMOL-Phos bearing hydrogen-bond donors as a privileged P-ligand for catalytic asymmetric hydrosilylation that is operationally simple and has 100% atom-economy with good functional group tolerability as well as high enantioselectivity (up to >99:1 er). Benefiting from the trans-selective hydrosilylation with the aid of Rh/Ar-BINMOL-Phos-based asymmetric catalysis, the Si-stereogenic benzosiloles exhibited pronounced aggregation-induced emission (AIE) and circularly polarized luminescence (CPL) activity.

Stereospecific Si-C coupling and remote control of axial chirality by enantioselective palladium-catalyzed hydrosilylation of maleimides.

Hydrosilylation of unsaturated carbon-carbon bonds with hydrosilanes is a very important process to access organosilicon compounds and ranks as one of the most fundamental reactions in organic chemistry. However, catalytic asymmetric hydrosilylation of activated alkenes and internal alkenes has proven elusive, due to competing reduction of carbon-carbon double bond or isomerization processes. Herein, we report a highly enantioselective Si-C coupling by hydrosilylation of carbonyl-activated alkenes using a palladium catalyst with a chiral TADDOL-derived phosphoramidite ligand, which inhibits O-hydrosilylation/olefin reduction. The stereospecific Si-C coupling/hydrosilylation of maleimides affords a series of silyl succinimides with up to 99% yield, >99:1 diastereoselectivity and >99:1 enantioselectivity. The high degree of stereoselectivity exerts remote control of axial chirality, leading to functionalized, axially chiral succinimides which are versatile building blocks. The product utility is highlighted by the enantioselective construction of N-heterocycles bearing up to three stereocenters.

Sulfonic acid-functionalized polyallylamine (sevelamer) as an efficient reusable strong solid acid catalyst for the synthesis of xanthenes derivatives.

Sevelamer (polyallyamine resin)-supported sulfonic acid (S-SO3H) has been prepared from the reaction of sevelamer with chlorosulfonic acid and characterized using FT-IR spectroscopy, scanning electronmicroscopy (SEM) and thermogravimetric analysis (TGA). The catalytic activity of S-SO3H was investigated in the synthesis of 1,8-dioxo-octahydroxanthene derivatives. All of the reactions were fast and gave excellent yields. The catalyst was easily recovered and reused for 5 runs without significant loss of its catalytic activity.

PdCl2(CH3CN)2-catalyzed regioselective C-H olefinations of 2-amino biaryls with vinylsilanes as unactivated alkenes.

The first example of palladium-catalyzed chelation-assisted C-H olefination of 2-amino biaryls using readily available vinylsilanes as unactivated olefinating reagents has been developed, affording valuable arylated vinylsilane compounds in moderate to excellent yields and with exclusive (E)-selectivities.

Desymmetrization-Oriented Enantioselective Synthesis of Silicon-Stereogenic Silanes by Palladium-Catalyzed C-H Olefinations.

A palladium-catalyzed chelation-assisted enantioselective C-H olefination of symmetrically diaryl-substituted tetraorganosilicon derivatives was developed, enabling the generation of nitrogen-containing silicon-stereogenic tetraorganosilicon compounds with modest to good yields and good to excellent enantioselectivities (up to 95.5:4.5 e.r.). The Thorpe-Ingold effect exerted by the substituents on silicon was observed to have a profound influence on formation of olefinated products which were further converted into other relevant chiral organosilanes without the loss of enantiomeric purity, thus demonstrating the synthetic utility of the developed enantioselective olefination.

Pd-Catalyzed Enantioselective Ring Opening/Cross-Coupling and Cyclopropanation of Cyclobutanones.

A palladium-catalyzed enantioselective sequential ring-opening/cross-coupling of cyclobutanones is disclosed that provides chiral indanones bearing C3-quaternary stereocenters. The reaction process involves palladium-catalyzed nucleophilic addition of cyclobutanones and aryl halides, enantioselective ß-carbon elimination, and intermolecular trapping of a transient σ-alkylpalladium complex with boronic acids. Alternatively, an intramolecular cyclopropanation is realized through C-H bond functionalization in the absence of external coupling reagents, affording chiral cyclopropane-fused-indanones in good yields and enantioselectivity.

Enantioselective synthesis of axially chiral vinyl arenes through palladium-catalyzed C-H olefination.

A palladium-catalyzed ketoxime-chelation-assisted enantioselective C-H olefination of 2-arylcyclohex-2-enone oxime ether with a wide range of olefins as coupling partners was developed. Employing ketoxime ether as an efficient directing group, a variety of axially chiral vinyl arenes was synthesized by Pd(ii)-catalyzed C-H functionalization with excellent enantioselectivities (96 → 99% ee) under mild conditions.

Ligand-Controlled Inversion of Diastereo- and Enantioselectivity in Silver-Catalyzed Azomethine Ylide-Imine Cycloaddition of Glycine Aldimino Esters with Imines.

A highly diastereo- and enantioselective silver-catalyzed azomethine ylide-imine (AYI) cycloaddition reaction of glycine aldimino esters with imines was developed in which the Xing-Phos-controlled syn-selective or DTBM-Segphos-induced anti-selective AYI cycloaddition reaction could be applied to the synthesis of a variety of stereodivergent 1-alkyl-2,5-substituted imidazolidines with high yields and excellent enantioselectivities (up to 99% ee) as well as good diastereoselectivities (up to 99:1 dr) under mild reaction conditions.

Palladium-catalyzed tandem allylic substitution/cyclization and cascade hydrosilylated reduction: the influence of reaction parameters and hydrosilanes on the stereoselectivity.

To shed light on the influence of reaction parameters on palladium-catalyzed tandem allylic alkylation in the presence of Fei-Phos (a chiral trans-1,2-diaminocyclohexane-derived phosphine ligand), the effect of different phosphine ligands, inorganic or organic bases, Brønsted acids, and other additives on the asymmetric palladium-catalysed alkylation of catechol with allylic diacetate was investigated. In this reaction, 2-vinyl-2,3-dihydro-benzo[1,4]dioxin products with promising enantioselectivity were achieved in good yields. In addition, a novel palladium-catalyzed three-component and one-pot allylic substitution/cyclization/reduction reaction assisted by methylphenylsilane was reported with good selectivity.

Catalytic asymmetric bromochlorination of aromatic allylic alcohols promoted by multifunctional Schiff base ligands.

It was found that the tridentate O,N,O-type Schiff base ligand bearing suitable substituents was a highly effective promoter in the catalytic asymmetric bromochlorination reaction, in which the corresponding aromatic bromochloroalcohols with vicinal halogen-bearing stereocenters were formed with perfect regioselectivity, with moderate to excellent enantioselectivities (up to 93% ee), and with good yields and chemoselectivities.

Development of a novel multifunctional n,p ligand for highly enantioselective palladium-catalyzed asymmetric allylic etherification of alcohols and silanols.

CycloN2P2-Phos! The use of the multidentate phosphine, CycloN2P2-Phos, which contains four heteroatoms (two nitrogen and two phosphorus atoms), in the palladium-catalyzed asymmetric allylic etherification (AAE) of alcohols and silanols leads to excellent levels of enantioselectivity (up to 99 % ee).

Copper-catalyzed Huisgen and oxidative Huisgen coupling reactions controlled by polysiloxane-supported amines (AFPs) for the divergent synthesis of triazoles and bistriazoles.

An interesting example of a divergent catalysis with a copper(I) and amine-functional macromolecular polysiloxanes system was successfully presented in click chemistry. In this manuscript, we demonstrate the remarkable ability of the secondary amine-functional polysiloxane to induce oxidative coupling in the copper-mediated Huisgen reactions of azides and alkynes, thereby achieving good yields and selectivities. The click reactions mediated by a polysiloxane-supported secondary amine allow the preparation of novel heterocyclic compounds, that is, bistriazoles. Comparably, it is also surprising that the use of a diamine-functional polysiloxane as ligand led to a classic Huisgen [3+2] cycloaddition in excellent yields. From the results of the present amine-functional polysiloxanes-controlled Huisgen reaction or oxidative Huisgen coupling reaction to divergent products and the proposed mechanism, we suggested that the mononuclear bistriazole-copper complex stabilized and dispersed by the secondary amine-functional polysiloxane was beneficial to prevalent the way to oxidative coupling.

Organocatalytic aza-Michael/retro-aza-Michael reaction: pronounced chirality amplification in aza-Michael reaction and racemization via retro-aza-Michael reaction.

A detailed experimental investigation of an aza-Michael reaction of aniline and chalcone is presented. A series of Cinchona alkaloid-derived organocatalysts with different functional groups were prepared and used in the aza-Michael and retro-aza-Michael reaction. There was an interesting finding that a complete reversal of stereoselectivity when a benzoyl group was introduced to the cinchonine and cinchonidine. The chirality amplification vs. time proceeds in the quinine-derived organocatalyst containing silicon-based bulky group, QN-TBS, -catalyzed aza-Michael reaction under solvent-free conditions. In addition, we have demonstrated for the first time that racemization was occurred in suitable solvents under mild conditions due to retro-aza-Michael reaction of the Michael adduct of aniline with chalcone. These indicate the equilibrium of retro-aza-Michael reaction and aza-Michael reaction produce the happening of chirality amplification in aza-Michael reaction and racemization via retro-aza-Michael reaction under different conditions, which would be beneficial to the development of novel chiral catalysts for the aza-Michael reactions.

[Establishment of cell line transfected with human BTLA gene and preliminary study on its biological function].

AIM: To establish 293T cells expressing human BTLA gene, a novel attenuator for B and T lymphocyte. METHODS: The gene encoding human BTLA was amplified by RT-PCR from PHA activated T cells, and then the target gene fragment was inserted into retrovirus vector pEGZ-Term after being digested with EcoR I and BamH I. The recombinant vector was transfected into 293T cells with LipfectAMINE 2000, and the cells was further selected with Zeocin. Effect of 293T/BTLA cells on T cells proliferation and activation in vitro was been studied by methods of MTT and cytometry. RESULTS: The stable expression of human BTLA on the transfected cell line was identified by flow cytometry analysis. In vitro, 293T/BTLA cells had an inhibitory effect on the proliferation of T cells stimulated by anti-CD3 mAb and down-regulated the expression of activation marker CD25 on the surface of T cells and decreased the secretion of IFN-gamma and IL-10. CONCLUSION: A cell line 293T/BTLA stably expressing the human BTLA protein has been obtained and it can partially inhibit the proliferation and activation of T cells in vitro.