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The asymmetric catalytic addition of linear Grignard reagents to ketones has been a long-standing challenge in organic synthesis. Herein, a novel family of PNP ligands (W-Phos) was designed and applied in copper-catalyzed asymmetric addition of linear Grignard reagents to aryl alkyl ketones, allowing facile access to versatile chiral tertiary alcohols in good to high yields with excellent enantioselectivities (up to 94 % yield, 96 % ee). The process can also be used to synthesize chiral allylic tertiary alcohols from more challenging α,β-unsaturated ketones. Notably, the potential utility of this method is demonstrated in the gram-scale synthesis and modification of various densely functionalized medicinally relevant molecules.

Transition-metal-catalyzed activations of carbon-carbons bonds of small strained rings have widespread applications in synthetic and medicinal chemistry. However, coupling reactions of cyclobutanols involving β-carbon elimination to construct C(sp3)-C(sp3) bonds have scarcely been developed. Here, we demonstrate a highly enantioselective Pd-catalyzed intermolecular C(sp3)-C(sp3) coupling reaction of a broad range of cyclobutanol derivatives and unactivated alkenes, allowing convenient access to a series of chiral benzene-fused cyclic compounds in a highly regio-, chemo-, and enantioselective manner.

Enabled by the newly developed ligand, Ming-Phos, the first example of palladium-catalyzed highly enantioselective coupling of racemic propargylic benzoates with organoboronic acids for chiral allenes synthesis has been developed. Excellent asymmetric induction has been achieved with a decent substrate scope. Synthetic potentials for the construction of polycyclic compounds with multiple chiral centers have been demonstrated.

Sonogashira-type cross-couplings are one of the most significant alkynylations in organic chemistry. One of the first palladium-catalyzed intramolecular Heck/Sonogashira reactions of alkenes with terminal alkynes is now reported. With this method, a variety of uniquely substituted chiral benzene-fused heterocycles bearing a propargyl-substituted all-carbon quaternary stereocenter were obtained in a straightforward, high-yielding, and highly stereoselective manner under mild conditions. Salient features of this process include the use of readily available substrates, high selectivities, a broad substrate scope as well as versatile product functionalizations.

A palladium catalyzed enantioselective Heck/borylation reaction of alkene-tethered aryl iodides was realized, delivering a variety of 2,3-dihydrobenzofuranyl boronic esters in high yield with excellent enantioselectivity. Asymmetric synthesis of chromane boronic ester, indane boronic ester and indoline boronic ester was also accomplished. The protocol offers an efficient access to the corresponding chiral benzocyclic boronic esters, which are notably important chemical motifs in synthetic transformations.

A highly enantioselective palladium-catalyzed iodine atom transfer cycloisomerization of unactivated alkenes has been developed. This represents the first example of highly enantioselective carboiodination of olefin-tethered aryl iodides, which provides a perfect atom economy method to construct a series of optically active 2,3-dihydrobenzofuran, indolines and chromane bearing an alkyl iodide group in moderate to good yields. Moreover, the use of readily available starting materials, a broad substrate scope, high selectivity, mild reaction conditions, as well as versatile transformation of the product make this approach attractive. The mechanism of this Pd(0)-catalyzed asymmetric carboiodination of alkenes has been investigated with density functional theory.

The highly exo- and enantioselective gold-catalyzed tandem heterocyclization/[4 + 3] cycloaddition of 2-(1-alkynyl)-2-alken-1-ones and 1,3-diphenylisobenzofuran was implemented by utilizing Ming-Phos, which provides a facile access to chiral seven-membered oxa-bridged rings in 80-98% yield with high exo selectivity ( exo/ endo up to 50:1) and up to 97% ee.

A newly developed Ming-Phos ligand with a 3,5-bis(trifluoromethyl)phenyl substituent was demonstrated to be highly efficient for Ag-catalyzed asymmetric [3 + 2] cycloaddition reactions of azomethine ylides with maleimides, cyclopentene-1,3-diones, and N-(2-t-butylphenyl)maleimide. Being easily prepared on the gram scale in one step, the ligand in combination with a Ag catalyst enables the synthesis of a variety of highly functionalized bicyclic pyrrolidine derivatives in good yields and excellent enantioselectivities under mild conditions.

The first intramolecular enantioselective cyclopropanation of indenes and trisubstituted alkenes was accomplished by using new chiral phosphine X5 derived gold(I) complexes. This reaction is a straightforward, efficient method for constructing [5-3-6] fused-ring compounds with two vicinal all-carbon quaternary stereogenic centers, a core structure shared by numerous pharmacological products, and bioactive compounds. The salient features of this transformation include high enantioselectivity (up to >98% ee), excellent yield (>97%), and nice functional group tolerance.

Heck-type C-H bond activation of unactivated alkenes has emerged as a powerful strategy for the construction of synthetically valuable spirocycles over past 30 years, however, the development of asymmetric version has lagged largely behind. Herein we demonstrate a robust Heck-type reaction of a broad range of unactivated alkenes enabled by the first palladium/Xu-Phos-catalyzed tandem Heck/remote C−H bond alkylation. Moreover, both enantiomers of the product can be efficiently prepared using the same enantiomer of a chiral ligand via a position of the phenyl ring-dependent enantiodivergent synthesis. The salient features of this methodology include operational simplicity, high chemo- and enantioselectivity, broad substrate scope. In addition, we first revealed that the C(sp2)-H activation, alkene insertion and C−I reductive elimination steps are reversible by experiments.

The first example of highly enantioselective intramolecular hydroarylation of allyl aryl ethers was realized by palladium-catalyzed reductive heck reactions utilizing a new chiral sulfinamide phosphine ligand (N-Me-XuPhos). N-Me-XuPhos can be easily prepared on gram scale from readily available starting materials in a one-pot synthesis approach. A series of optically active 2,3-dihydrobenzofurans bearing a quaternary stereocenter were obtained in good yields and with excellent enantioselectivities. The practicality of this reaction was validated in the straightforward synthesis of CB2 receptor agonists. Moreover, deuterium was efficiently incorporated into the products.

A highly enantioselective copper-catalyzed [3 + 2] cycloaddition reaction of α-isocyanoesters with β,β-disubstituted enones has been developed. Dihydropyrroles were obtained in excellent yields and enantioselectivity by employing an inexpensive copper catalyst. This process provides a scalable and efficient route for the synthesis of highly enantioselective 2,3-dihydropyrroles bearing a trifluoromethylated all-carbon quaternary stereocenter. The salient feautures of this reaction include high efficiency, operational simplicity, high diastereoselectivity and enantioselectivity, a broad substrate scope, outstanding functional group tolerance, and products exhibiting high utility for further transformations.

Highly enantioselective gold-catalyzed intramolecular cyclization of N-allenamides was implemented by utilizing a designed chiral sulfinamide phosphine ligand (PC-Phos). This represents the first example of highly enantioselective intramolecular cyclization of N-allenamides. The practicality of this reaction was validated in the total synthesis of (R)-desbromoarborescidine A and formal synthesis of (R)-desbromoarborescidine C and (R)-deplancheine. Moreover, the catalyst system PC-Phos/AuNTf2 proved to be specifically efficient to promote the desymmetrization of N-allenamides in excellent yields with satisfactory ee values.

Supported metal nanoparticles (NPs) catalysts in constructing benzene-fused cyclic framework with chirality is very challenging. Dihydrobenzofuran and its derivatives are significant heterocyclic units in biologically molecules. Herein, size-controlled Pd NPs fixed on mesoporous silica (Pd/MS-xT) SBA-15, FDU-12 and mesocellular silica foams (MCFs) were utilized to synthesize racemic and asymmetric iodomethyl dihydrobenzofuran for the first time. The size of Pd NPs was regulated by increasing NaBH4 reduction treatments times (-xT) and enlarging supports pore. Based on large mesopore of MCF-3, supported catalyst 3%Pd/MCF-3-4T possessed larger Pd size gave the excellent performance at 92% racemic yield. Under chiral phosphine modifier N–Me-Xu3, we implemented more deserving asymmetric reaction over 3%Pd/MCF-3-1T with smaller Pd NPs. TGA for organic surface coverage demonstrated that the substrate preferred larger Pd NPs, N–Me-Xu3 capped more easily on smaller ones. Besides, effects of reaction medium and N–Me-Xu3 additive quantity further revealed the coordination of chiral modifier on Pd/MCF-3 was the determinant. For broader visions, the performance dependence based on surface properties of heterogeneous catalyst would play crucial contributions towards construction of complexed organic molecules.

The employment of β,β-disubstituted enones as dipolarophiles poses a considerable challenge due to their steric hindrance and low reactivity. A copper-catalyzed asymmetric exo-selective dipolar cycloaddition of β-trifluoromethyl β,β-disubstituted enones with azomethine ylides was developed, which provides an efficient access to valuable pyrrolidines bearing a trifluoromethylated all-carbon quaternary stereocenter. Up to quantitative yields with up to >20 : 1 dr and 99% ee were delivered. A broad substrate scope, good functional group tolerance, high stereoselectivity, as well as diverse synthetically valuable transformations of the products make this approach highly attractive.

The employment of α-trifluoromethyl α,β-unsaturated esters as dipolarophiles pose considerable challenge due to expeditious defluorination and intrinsic steric hindrance. The present work provides an efficient access to valuable pyrrolidines bearing a trifluoromethylated all-carbon quaternary stereocenter through copper/M7-catalyzed asymmetric dipolar cycloaddition of α-trifluoromethyl α,β-unsaturated esters with azomethine ylides. The products were obtained in up to 98% yield with up to >20:1 d.r. and 99% ee. A broad substrate scope, good functional group tolerance, high stereoselectivity, as well as diverse synthetically valuable transformations of the products make this approach highly attractive.

A highly enantioselective dicarbofunctionalization of unactivated alkenes was implemented by a Pd-catalyzed asymmetric tandem Heck/Suzuki coupling reaction. This reaction represents the first example of a highly enantioselective intramolecular cyclization/cross-coupling of olefin-tethered aryl halides with alkyl-, alkenyl- or arylboronic acids, and provides rapid access to a number of chiral compounds, such as dihydrobenzofurans, indolines, chromanes, and indanes bearing a quaternary stereocenter, in good yields with excellent enantioselectivities. The practicality of this reaction was validated in the modification of biologically complex molecules such as peptides, piperitol, CB2 receptor agonists, etc. Moreover, the synthesis of two enantiomers can be easily realized by simple change in the order of the steps in the coupling sequence.

A highly enantioselective gold(I)-catalyzed intermolecular tandem cyclization/[3 + 2] cycloaddition of 2-(1-alkynyl)-2-alken-1-ones with 3-stylindoles was achieved by using Ming-Phos as a chiral ligand. A variety of chiral highly substituted cyclopenta[c]furans were obtained in good yields (up to 99%) with excellent diastereoselectivities (>20:1) and enantioselectivities (up to 97% ee). The salient features of the present protocol include mild conditions, excellent yields, and high diastereo- and enantioselectivities, using readily available starting materials and a chiral ligand.

Reported herein is an asymmetric [3+2] cycloaddition reaction of azomethine ylides with β-trifluoromethyl β,β-disubstituted enones, a reaction which is enabled by a Ming-Phos-derived copper(I) catalyst (Ming-Phos=chiral sulfinamide monophosphines, Figure 1). This method provides scalable and efficient access to the highly substituted pyrrolidines with a trifluoromethylated, all-carbon quaternary stereocenter in good yields with up to greater than 20:1 d.r. and 98 % ee. The reaction has a broad substrate scope and tolerates a wide range of functional groups.

The enantioselective intermolecular [2 + 2] cycloaddition of 3-styrylindoles with N-allenyl oxazolidinone has been achieved for the first time by the employment of a Xiang-Phos derived chiral gold-catalyst. The corresponding cycloadducts could be obtained in good yields (up to 95%) with up to 95% ee.

The polymer-bound Ming-Phos was easily prepared by the highly efficient immobilization of our recently developed Ming-Phos in polystyrene by copolymerization in the presence of 5% DVB, which shows good performance in the application of heterogeneously catalyzed asymmetric cycloaddition. A pair of enantiomers of the product with opposite configurations could be easily delivered in high yields with excellent enantioselectivity by the application of two diastereomers of the heterogeneous catalyst. This heterogeneous catalyst not only exhibits similar catalytic activity and enantioselectivity to those of the homogeneous catalyst but also could be easily recovered and recycled for up to eight cycles.

An unprecedented ligand-controlled regiodivergent Cu(I)-catalyzed asymmetric intermolecular (3 + 2) cycloaddition reaction of α-substituted iminoesters with β-fluoromethyl β,β-disubstituted enones was developed. This novel strategy provides an efficient method for the enantioselective regiodivergent synthesis of pyrrolidines bearing two adjacent quaternary stereocenters or two discrete quaternary stereocenters, opening up a new era for medicinal chemistry and diversity-oriented synthesis. DFT calculations showed that the P,N-ligand L2 acts as a pseudobidentate ligand. The formation of a O-Cu bond with the carbonyl oxygen atom of the enone and dissociation of the amine nitrogen of L2 from the Cu(I) center occurs during the catalytic cycle; this is the main reason for the tuning the regioselectivity of the cycloaddition reaction caused by switching of the ligand. The salient features of this work include high yields (up to99%), a general substrate scope, the use of commercially available ligands, and high regio-(up to20:1 rr), diastereo- (up to20:1 dr), and enantioselectivity (up to99% ee).

A simple, new type of chiral sulfinamide monophosphines, the so-called Ming-Phos ligands, is reported; these ligands could be easily prepared from inexpensive and commercially available starting materials. The Ming-Phos ligands performed well in the enantioselective gold-catalyzed cycloaddition reaction of 2-(1-alkynyl)-alk-2-en-1-ones with nitrones. Both enantiomers of the products could be obtained in good yields and with excellent diastereo- and enantioselectivity through transformations that were catalyzed by gold complexes derived from two diastereomers of Ming-Phos ligand M5 (Ar=1-naphthyl).

The enantioselective intermolecular [2 + 2] cycloaddition of 3-styrylindoles with N-allenyl oxazolidinone has been achieved for the first time by the employment of a Xiang-Phos derived chiral gold-catalyst. The corresponding cycloadducts could be obtained in good yields (up to 95%) with up to 95% ee.

Reported herein is an asymmetric [3+2] cycloaddition reaction of azomethine ylides with β-trifluoromethyl β,β-disubstituted enones, a reaction which is enabled by a Ming-Phos-derived copper(I) catalyst (Ming-Phos=chiral sulfinamide monophosphines, Figure 1). This method provides scalable and efficient access to the highly substituted pyrrolidines with a trifluoromethylated, all-carbon quaternary stereocenter in good yields with up to greater than 20:1 d.r. and 98 % ee. The reaction has a broad substrate scope and tolerates a wide range of functional groups.

It has been reported that Arabidopsis thaliana leaf trichome can act as a mechanosensory switch, transducing mechanical stimuli into physiological signals, mainly through a buckling instability to focus external force (e.g., exerted by insects) on the base of trichome. The material and structural properties of trichomes remain largely unknown in this buckling instability. In this report, we mainly focused on material standpoint to explore the possible mechanism facilitating the buckling instability. We observed that the Young's modulus of trichome cell wall decreased gradually from branch to the base region of trichome. Interestingly, we also found a corresponding decline of calcium concentration on the trichome cell wall. Results of finite element method (FEM) simulation suggested that such a gradient distribution of Young's modulus significantly promotes force focusing and buckling instability on the base of trichome. It is indicated that Arabidopsis trichome has developed into an active mechanosensor benefiting from gradient cell wall mechanical properties.

The new title ligands can be easily prepared from inexpensive and commercially available starting materials.

The dependence of the adatom diffusion on the strained (1 1 1) surface of Cu metal was investigated using molecular dynamics simulation. It is found that the diffusion coefficient of the Cu adatom on Cu surface decreases with increasing tensile strain at different temperatures where we studied. On the strained surface, the diffusion coefficient still exhibits approximately Arrhenius behavior. The main diffusion is the hopping diffusion. While, with the temperature or the tensile strain raised further, the exchange diffusion appears. And its frequency will increase with these values.

The mechanical properties of single-walled nanotubes (SWNTs) filled with small fullerenes (C20, C36 and C60) were investigated using molecular dynamics (MD) simulation. The interaction between carbon atoms was described by a combination of the many-body Brenner potential with a two-body pair potential. We found that below the critical value of the strain, the stress of SWNT increases linearly with the strain and the Young's modulus of certain SWNT with different filling densities is almost the same for small strain. It was also observed that the buckling force, which corresponds to the critical strain, becomes higher as the filling density of SWNT is increased in general. However, in the case of SWNT of larger radius filled with smaller fullerenes, the dependence of the buckling force on the filling density is expected to be different, which was attributive to the long-distance attractive interaction between atoms of fullerene and those of SWNT.

To study the diagnostic value of anti-cyclic citrullinated peptide antibody (anti-CCP) and magnetic resonance imaging (MRI) of metacarpophalangeal joints (MCP) and wrist in early rheumatoid arthritis (RA).MRI of MCP and wrist joint, laboratory indices of anti-CCP and rheumatic factor (RF) were performed and recorded in the 94 early-stage RA patients, 24 non-typical monoarthritis and 35 other arthritis. The MRI findings and OMERACT (outcome measures in rheumatoid arthritis clinical trials) score were analyzed in comparison with their clinical and laboratory indices.The sensitivity of anti-CCP, synovitis, bone erosion and bone erosion was 55.3%, 100%, 25.5% and 88.3% respectively in early-stage RA patients. The specificity was 88.6%, 71.4%, 94.3% and 65.7% respectively. There was significant difference between early-stage RA group and other arthritis group (P0.05). Bone erosion was found to be the most specific among MRI findings. And bone erosion of wrist joint had a positive correlation with anti-CCP. MRI was a more efficient supplemental modality in diagnosing early-stage RA as compared with conventional radiological films. Among 94 early-stage RA, their MRI findings and OMERACT scores of wrist joint appeared more obvious.Anti-CCP has a better specificity for early-stage RA than RF. But MRI may visualize the disorder of RA earlier while it is often missed by radiological films. Both have prominent diagnostic values in early RA patients. Bone erosion of wrist joint has a positive correlation with anti-CCP. MRI may help to differentiate those RA patients with negative anti-CCP.

The sulphur dioxide content and thermal stability of the quinol-SO2 clathrate have been studied by thermogravimetric analysis (TG), its derivative (DTG) and differential scanning calorimetry (DSC). These analyses demonstrated the thermal recoverability of the quinol from the clathrate and hence its potential use as a sponge for SO2 present in the environment as a pollutant. Similarly, Bu4N(+)I(-) was found to occlude NO2 and SO2 at 50°C in solution.