RESUMO
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.
RESUMO
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.
RESUMO
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.
RESUMO
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.
RESUMO
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%.
RESUMO
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.
Assuntos
Indolquinonas , Estereoisomerismo , CiclizaçãoRESUMO
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.
Assuntos
Cobre , Indolquinonas , Catálise , MetaisRESUMO
A sequential enantioselective conjugate addition/hydroalkoxylation between in situ generated ortho-quinomethanes and ynones by combining bifunctional squaramide and DBU catalysis has been developed. A variety of eight-membered cyclic ethers with two contiguous tertiary stereocenters were obtained in high yields with excellent stereoselectivities. This reaction not only provides a new strategy for constructing enantioenriched eight-membered cyclic ethers but also demonstrates the practicability of ynones as C4-syntons for the synthesis of chiral medium-membered rings.