An Axially Chiral Styrene-Phosphine Ligand for Pd-Catalyzed Asymmetric N-Alkylation of Indoles.

An efficient palladium-catalyzed enantioselective direct N-alkylation of indoles using a novel type of axially chiral styrene-phosphine ligand SJTU-PHOS-1 was developed. This reaction demonstrated good functional group compatibility and a wide range scope of substrates in mild conditions. Moreover, the DFT calculations expounded the coordination mode of the metal catalyst and the axially chiral styrene-phosphine ligand in the enantioselectivity control.

Cu/Ni-Catalyzed Cyanomethylation of Alkenes with Acetonitrile for the Synthesis of ß,γ-Unsaturated Nitriles.

We have developed a protocol for the Cu/Ni-catalyzed cyanomethylation of alkenes with acetonitrile for the synthesis of ß,γ-unsaturated nitriles. This is the first example of a direct coupling of the alkene sp2 C-H bond and the acetonitrile sp3 C-H bond for the preparation of ß,γ-unsaturated nitriles. Acetonitrile, an inexpensive and stable solvent, is demonstrated to be a useful cyanomethyl source. The combination of copper and nickel catalysts resulted in a high reaction efficiency.

Palladium-catalyzed allylic C-H oxidation under simple operation and mild conditions.

We discovered an effective and simple system (Pd/BQ/air/r.t.) for making allylic alcohols through Pd-catalyzed allylic C-H bond functionalization. This approach exhibits advantages due to its simple operation, mild conditions, and environmentally benign features. By modifying reaction conditions, it can be suitable for preparing unsaturated aldehydes, allylic esters, ethers, and amines.

Hydrochloric Acid-Promoted Intermolecular 1,2-Thiofunctionalization of Aromatic Alkenes.

An efficient method for making 1,2-thiofunctionalized products via the difunctionalization of aromatic alkenes was developed. In this method, cheap and readily available hydrochloric acid was used to promote 1,2-thiofunctionalization of aryl alkenes with N-arylsulfenylphthalimide and different types of nucleophiles. Importantly, extension of nucleophiles can reach aryl ethers, indoles, and carboxylic acids with good reactivity. This practical and convenient method has broad substrate scope and high yields under metal-free and mild conditions. Furthermore, we achieved conversion and application for making sulfoxide and sulfone by oxidation.

Alkyne Hydroheteroarylation: Enantioselective Coupling of Indoles and Alkynes via Rh-Hydride Catalysis.

We report an enantioselective coupling between alkynes and indoles. A Rh-hydride catalyst isomerizes alkynes to generate a metal-allyl species that can be trapped with both aromatic and heteroaromatic nucleophiles.

Copper-catalyzed aromatic C-H alkoxylation with alcohols under aerobic conditions.

An efficient protocol for copper-catalyzed aromatic C-H alkoxylation with alcohols has been developed under aerobic conditions. The protocol provides a complementary method to couple arenes and alcohols to furnish aromatic ethers. The advantages of this method are the employment of a cheap Cu(OAc)2 catalyst, oxygen as the terminal oxidant and alcohol as both an alkoxy reagent and a solvent. Notably, the catalytic amount of benzoic acid plays a significant role in this transformation.

Cu-Catalyzed Cyanation of Arylboronic Acids with Acetonitrile: A Dual Role of TEMPO.

The cyanation of arylboronic acids by using acetonitrile as the "CN" source has been achieved under a Cu(cat.)/TEMPO system (TEMPO=2,2,6,6-tetramethylpiperidine N-oxide). The broad substrate scope includes a variety of electron-rich and electron-poor arylboronic acids, which react well to give the cyanated products in high to excellent yields. Mechanistic studies reveal that TEMPO-CH2 CN, generated in situ, is an active cyanating reagent, and shows high reactivity for the formation of the CN(-) moiety. Moreover, TEMPO acts as a cheap oxidant to enable the reaction to be catalytic in copper.

Cu-Catalyzed Cyanation of Indoles with Acetonitrile as a Cyano Source.

Cu-catalyzed cyanation of indoles with acetonitrile for the synthesis of 3-cyanoindoles has been developed. The Cu/TEMPO/(Me3Si)2 system has been identified to promote highly efficient and selective C-H cyanation of indoles by use of unactivated acetonitrile as a cyano source via a sequential iodination/cyanation process in one pot. This reaction furnishes 3-cyanoindoles in moderate to good yields and tolerates a series of functional groups. Moreover, low-cost copper catalysts and hazardless acetonitrile as a cyano source feature the practicability of this reaction.

Cu-catalyzed direct amidation of aromatic C-H bonds: an access to arylamines.

A Cu-catalyzed aromatic C-H amidation with phthalimide under oxygen as a terminal oxidant without using additional additives has been achieved. This reaction has the broad substrate scope and shows moderate to good yields in most cases. This method is complementary to the previously reported metal-catalyzed C-H amination systems.

Copper-catalyzed aromatic C-H bond halogenation with lithium halides under aerobic conditions.

A concise and practical Cu-catalyzed protocol for the preparation of chloro- and bromoarenes via C-H bond activation has been developed. The advantages of this strategy are the employment of cheap Cu(NO3)2·3H2O, LiX and O2, and its compatibility with both electron-donating and electron-withdrawing substituents on aryl rings.

Palladium-catalyzed intramolecular decarboxylative coupling of arene carboxylic acids/esters with aryl bromides.

Give me a ring? An efficient approach has been developed for the intramolecular decarboxylative coupling of arene carboxylic acids/esters with aryl bromides catalyzed by palladium (see scheme). From a synthetic viewpoint, this method is highly attractive because the catalyst loading is low, the optimized reaction conditions are mild, and the substrate scope is broad.

Mechanistic insights into the rhodium-catalyzed intramolecular ketone hydroacylation.

[Rh((R)-DTBM-SEGPHOS)]BF(4) catalyzes the intramolecular hydroacylation of ketones to afford seven-membered lactones in large enantiomeric excess. Herein, we present a combined experimental and theoretical study to elucidate the mechanism and origin of selectivity in this C-H bond activation process. Evidence is presented for a mechanistic pathway involving three key steps: (1) rhodium(I) oxidative addition into the aldehyde C-H bond, (2) insertion of the ketone CO double bond into the rhodium hydride, and (3) C-O bond-forming reductive elimination. Kinetic isotope effects and Hammett plot studies support that ketone insertion is the turnover-limiting step. Detailed kinetic experiments were performed using both 1,3-bis(diphenylphosphino)propane (dppp) and (R)-DTBM-SEGPHOS as ligands. With dppp, the keto-aldehyde substrate assists in dissociating a dimeric precatalyst 8 and binds an active monomeric catalyst 9. With [Rh((R)-DTBM-SEGPHOS)]BF(4), there is no induction period and both substrate and product inhibition are observed. In addition, competitive decarbonylation produces a catalytically inactive rhodium carbonyl species that accumulates over the course of the reaction. Both mechanisms were modeled with a kinetics simulation program, and the models were consistent with the experimental data. Density functional theory calculations were performed to understand more elusive details of this transformation. These simulations support that the ketone insertion step has the highest energy transition state and reveal an unexpected interaction between the carbonyl-oxygen lone pair and a Rh d-orbital in this transition state structure. Finally, a model based on the calculated transition-state geometry is proposed to rationalize the absolute sense of enantioinduction observed using (R)-DTBM-SEGPHOS as the chiral ligand.

Direct Synthesis of Alkenylboronates from Alkenes and Pinacol Diboron via Copper Catalysis.

We report an efficient approach for the direct synthesis of alkenylboronates using copper catalysis. The Cu/TEMPO catalyst system (where TEMPO = (2,2,6,6-tetramethylpiperidin-1-yl)oxyl) exhibits both excellent reactivity and selectivity for the synthesis of alkenylboronates, starting from inexpensive and abundant alkenes and pinacol diboron. This approach allows for the direct functionalization of both aromatic and aliphatic terminal alkenes. Mechanistic experiments suggest that the alkenylboronates arise from oxyboration intermediates.

Acetonitrile as a cyanating reagent: Cu-catalyzed cyanation of arenes.

A novel approach to the Cu-catalyzed cyanation of simple arenes using acetonitrile as an attractive cyano source has been documented. The C-H functionalization of arenes without directing groups involves a sequential iodination/cyanation to give the desired aromatic nitriles in good yields. A highly efficient Cu/TEMPO system for acetonitrile C-CN bond cleavage has been discovered. TEMPO is used as a cheap oxidant and enables the reaction to be catalytic in copper. Moreover, TEMPOCH2CN 6 has been identified as the active cyanating agent and shows high reactivity for forming the -CN moiety.

MRC-SPECT: A sub-500 µm resolution MR-compatible SPECT system for simultaneous dual-modality study of small animals.

In this paper, we will report the development of an ultrahigh resolution MR-compatible SPECT system that can be operated inside a pre-existing clinical MR scanner for simultaneous dual-modality imaging of small animals. This system is constructed with 40 small-pixel CdTe detector modules assembled in a fully stationary ring SPECT geometry. We have experimentally demonstrated that this system is capable of providing an imaging resolution of <500 µm when operating inside MR scanners. We will report the design, construction of the MRI-compatible SPECT system, including the detector technology, collimator, system development and so on. The first imaging results obtained with this newly constructed SPECT system will also be reported.