Synthesis of Chiral Diarylmethylamides via Catalytic Asymmetric Aza-Michael Addition of Amides to ortho-Quinomethanes.

Chiral diarylmethylamides are a privileged skeleton in many bioactive molecules. However, the enantioselective synthesis of such molecules remains a long-standing challenge in organic synthesis. Herein, we report a chiral bifunctional squaramide catalyzed asymmetric aza-Michael addition of amides to in situ generated ortho-quinomethanes, affording enantioenriched diarylmethylamides in good yields with excellent enantioselectivities. This work not only provides a new strategy for the construction of the diarylmethylamides but also represents the practicability of amides as nitrogen-nucleophiles in asymmetric organocatalysis.

Diastereo- and Enantioselective Synthesis of Eight-Membered N-Heterocycles from Benzofuran-Derived Azadienes and Ynones.

Enantioselective synthesis of eight-membered N-heterocycles represents a long-standing challenge in organic synthesis. Here, by combining the squaramide and DBU catalysis, a sequential asymmetric conjugate addition/cyclization reaction between benzofuran-derived azadienes and ynones has been well-developed, providing straightforward access to chiral eight-membered N-heterocycles in high yields with stereoselectivities. This protocol features the use of a bifunctional squaramide catalyst for controlling the enantioselectivity of products, while the DBU is utilized to achieve intramolecular cyclization and improve the diastereoselectivity of products.

Metal-free and enantioselective synthesis of 1,4-benzoxazepines from para-quinone methide derivatives and α-bromohydroxamates.

A sequential asymmetric conjugate addition/cyclisation of α-bromohydroxamates with para-quinone methide derivatives has been developed, which provides enantioenriched 1,4-benzoxazepines in generally high yields (up to 95%) and good enantioselectivities (up to 97 : 3 er). This protocol not only offers a novel and straightforward strategy for constructing chiral 1,4-benzoxazepines, but also demonstrates the potential of α-bromohydroxamates as three-atom synthons in asymmetric cyclisation reactions.

Copper-catalyzed asymmetric 1,6-conjugate addition of in situ generated para-quinone methides with ß-ketoesters.

A Cu-catalyzed asymmetric 1,6-conjugate addition of in situ generated para-quinone methides (p-QMs) with ß-ketoester has been developed to construct a ketoester skeleton bearing an adjacent tertiary-quaternary carbon stereocenter in good yields and high enantioselectivities. This is the first example of metal-catalyzed asymmetric transformations of the in situ generated p-QMs, avoiding using pre-synthesized p-QMs requiring bulky 2,6-substitutions and highlighting a new dual catalytic activation with the chiral bis(oxazoline)-metal complex acting as a normal Lewis acid to activate the ß-ketoesters and a source of Brønsted acid responsible for generating the p-QMs in situ.

Asymmetric bis(oxazoline)-Ni(II) catalyzed α-hydroxylation of cyclic ß-keto esters under visible light.

Using visible light as a driving force and molecular oxygen as a green oxidant, we developed bis(oxazoline)-Ni(acac)2 catalyzed asymmetric α-hydroxylation of ß-keto esters under low photosensitizer loading, and the protocol enabled an efficient transformation to provide the desired chiral α-hydroxy-ß-keto esters in high yields (up to 99%) and enantioselectivities (up to 99% ee) at room temperature.

Regio- and Enantioselective Friedel-Crafts Benzhydrylation of Indoles in Carbocyclic Ring with ortho-Quinomethanes: Access to Chiral Diarylindolylmethanes.

The functionalization of indoles in the carbocyclic ring has been achieved via organocatalytic enantioselective Friedel-Crafts benzhydrylation of hydroxyindoles with in situ generated ortho-quinomethanes in oil-water biphases, allowing an efficient access to varied diarylindolylmethanes with a wide substrate scope. The high yields, excellent stereoselectivities, mild conditions, low catalyst loading, and easy scalability also demonstrated the interest of this novel methodology.

Asymmetric copper-catalyzed fluorination of cyclic ß-keto esters in a continuous-flow microreactor.

A highly enantioselective homogeneous fluorination of cyclic ß-keto esters catalyzed by diphenylamine linked bis(oxazoline)-Cu(OTf)2 complexes has been established in a continuous flow microreactor. The microreactor allowed an efficient transformation with reaction times ranging from 0.5 to 20 min, and the desired products were afforded in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee) at a low catalyst loading of 1 mol%.

Regioselective catalytic asymmetric N-alkylation of isoxazol-5-ones with para-quinone methides.

A highly regioselective and enantioselective N-alkylation of isoxazol-5-ones with para-quinone methides promoted by bi-functional squaramide catalysts was developed. This unexpected asymmetric N-addition of isoxazolinones afforded a series of enantioenriched N-diarylmethane substituted isoxazolinones with high yields and enantioselectivities (up to 97 : 3 er). This reaction not only provides a useful approach for intermolecular chiral C-N bond formation but also demonstrates the immense potential of isoxazol-5-ones as N-nucleophiles in catalytic asymmetric reactions.

Development of ELISA for metallothionein-II allows determination of heavy metal pollution of fresh water.

Metallothionein (MT), a metal-binding protein induced primarily by heavy metals in vertebrates, is considered a biomarker for environmental heavy-metal contamination. To investigate heavy metal pollution in the freshwater environment, MT-I and MT-II were purified from livers of crucian carp (Carassius carassius) by gel exclusion chromatography and ion exchange chromatography. To detect the purified MT-II, a specific monoclonal antibody (mAb) against crucian carp MT-II was produced from the hybridoma strains by cell-cell fusion. By using Enzyme-Linked Immunosorbent Assay (ELISA) with this mAb, the purified crucian carp MT-II was detected with a high specificity and sensitivity. There was a good correlation between the amount of MT-II in carp livers and the concentration of heavy metals in water. ELISA was then used to evaluated the degree of heavy metal pollution in two freshwater systems. The results indicate that the MT-II content in carp liver tissue can be used as an indicator of environmental heavy-metal pollution.