Gold-Catalyzed Desymmetric Lactonization of Alkynylmalonic Acids Enabled by Chiral Bifunctional P,N ligands.

Due to the linear coordination nature of gold(I) catalysts, achieving high enantiocontrol in asymmetric gold catalysis is a great challenge. To improve the enantiocontrol of gold catalysis, an ion-pairing strategy was therefore proposed. A series of bifunctional P,N ligands based on chiral spirocyclic and biaryl scaffolds were synthesized and applied in the gold(I)-catalyzed desymmetric lactonization of alkynylmalonic acids. A wide range of chiral lactones containing an α-position quaternary stereocenter were synthesized with high yields, excellent regioselectivity and enantioselectivity under mild reaction conditions. The synthetic utilities of the current reaction were demonstrated by gram-scale synthesis and transformations of chiral lactones. The origin of enantioselectivity and the role of the alcohol additive were elucidated via control experiments and DFT calculations.

Design and Synthesis of Chiral oxa-Spirocyclic Ligands for Ir-Catalyzed Direct Asymmetric Reduction of Bringmann's Lactones with Molecular H2.

We herein present a facile and column-free synthetic route toward a structurally unique oxa-spirocyclic diphenol, termed as O-SPINOL. Features of the synthesis include the construction of the all-carbon quaternary center at an early stage, a key double intramolecular SNAr step to introduce the spirocycles and the feasibility of operating on >100 g scale. Both enantiomers of O-SPINOL can be easily accessed through optical resolution with l-proline by control of the solvent. The chiral tridentate ligand O-SpiroPAP derived from O-SPINOL has been successfully synthesized and applied in the iridium-catalyzed asymmetric hydrogenation of bridged biaryl lactones under mild reaction conditions, providing valuable and enantioenriched axially chiral molecules in excellent yields and enantioselectivities (up to 99% yield and >99% ee). This method represents a rare example of constructing axially chiral molecules by direct reduction of esters with H2.

Gold-catalyzed highly enantioselective cycloadditions of 1,6-enynes and 1,6-diynes assisted by remote hydrogen bonding interaction.

Gold(I)-catalyzed highly enantioselective [4 + 2] cycloadditions of 1,6-enynes were achieved by utilizing chiral bifunctional P,N ligand. A wide range of 1,6-enynes were converted to enantioenriched 5-6-6-fused tricyclic compounds under mild reaction condition (up to 99% ee). This chiral gold(I) complex was also employed in the first desymmetric cycloadditions of 1,6-diynes bearing single ester group at the tether (up to 93% ee), where 5-exo-dig pathway predominates over 6-endo-dig pathway. DFT calculations and control experiments were performed to rationalize the origin of precise stereocontrol. It implies that hydrogen bonding interaction between the ester group of substrates and the secondary amine of the chiral P,N ligands plays a pivotal role in the control of enantioselectivity. The utilities of the current reaction were demonstrated by scale-up experiment and derivatizations.

Cobalt-Catalyzed Enantioselective Hydrogenation of Diaryl Ketones with Ferrocene-Based Secondary Phosphine Oxide Ligands.

A new class of cobalt catalytic system for asymmetric hydrogenation of ketones was herein reported, involving the development of novel ferrocene-based secondary phosphine oxide ligands. An unusual P-O bidentate coordination pattern with cobalt was confirmed by an X-ray diffraction study. The bichelating tetrahedral cobalt(II) complexes afforded high reactivities (up to 99% yield) and good to excellent enantioselectivities (up to 92% ee) in the AH of various ortho-substituted diaryl ketones. In addition, the diferrocenyl cobalt complex was characterized with intriguing UV-vis absorption and electrochemical properties.

Highly Enantioselective Rhodium(I)-Catalyzed Alder-ene-type Cycloisomerization of 1,7-Enynes.

The transition-metal-catalyzed asymmetric cycloisomerization of 1,7-enynes is regarded as a formidable challenge due to the poor ability of 1,7-enynes to serve as bidentate ligands to metal. In this Letter, a highly enantioselective rhodium(I)-catalyzed Alder-ene-type cycloisomerization of 1,7-enynes is disclosed, offering an efficient method for the synthesis of a wide range of fused six-membered cyclic compounds. Furthermore, a high turnover frequency experiment and deuterium-labeling experiment were performed to give insight into this transformation.

CuH-Catalyzed Atropoenantioselective Reduction of Bringmann's Lactones via Dynamic Kinetic Resolution.

A CuH-catalyzed atropoenantioselective reduction of Bringmann's lactones via dynamic kinetic resolution has been disclosed. This protocol features a broad substrate scope and good functional group tolerance and allows the rapid assembly of various valuable axially chiral biaryls in good to high yields (up to 92% yield) with high to excellent enantioselectivities (up to 96% ee). Moreover, this report represents a rare example that a carbonyl group of esters is reduced under homogeneous asymmetric CuH catalysis.

Pd(0)-CMC@Ce(OH)(4) organic/inorganic hybrid as highly active catalyst for the Suzuki-Miyaura reaction.

A very easy sequential metathesis for the synthesis of Pd(II)-CMC@Ce(OH)4 organic/inorganic hybrid and its application as effective pre-catalyst for the Suzuki-Miyaura reaction have been reported. It was found that the Pd nanoparticles (Pd NPs) were formed in situ in the course of the Suzuki-Miyaura couplings when Pd(II)-CMC@Ce(OH)4 was used as a pre-catalyst. The activity of the Pd NPs in the reaction was enhanced synergistically by the unique redox properties (Ce3+/Ce4+) of Ce(OH)4 and coordination with carboxyl groups as well as free hydroxyl groups of the hybrid of CMC@Ce(OH)4. The results exhibit the Pd(0)-CMC@Ce(OH)4 is super over Pd(II)@CMC, Pd(II)@CeO2, and Pd(II)@Ce(OH)4 catalysts in the Suzuki-Miyaura reaction. Moreover, the catalyst could be easily separated by simple filtration and reused at least seven runs without losing its activity.

[MSCT perfusion analysis of nasopharyngeal cancer].

OBJECTIVE: To study MSCT perfusion imaging of nasopharyngeal cancer and its differentiated diagnosis. METHOD: Thirty cases with nasopharyngeal cancer performed multi-detector CT perfusion examination. Among them, there were 6 cases of 25 post-radiotherapy patients performed perfusion imaging with CT scan. Nasopharynx perfusion parameters include blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface (PS). RESULT: Compared with normal region of nasopharynx, BF, BV and PS in nasopharyngeal cancer increased significantly, while MTT has not significant difference between these two areas. CONCLUSION: Nasopharynx perfusion parameters (BF, BV and PS) measured with CT were significantly altered in nasopharyngeal cancer. There was important appliance value in differentiated diagnosis of nasopharyngeal malignant neoplasms and evaluation of outcome of radiotherapy of nasopharyngeal cancer.