Herein, we report an enantioselective Pd/Cu-catalyzed sequential Heck/Sonogashira coupling reaction of electron-rich enamides with terminal alkynes as substrates. This transformation proceeds smoothly to afford 3-propargyl isoindolinone derivatives bearing quaternary stereogenic centers in moderate to good yields (43-77% yield) and good to excellent enantioselectivity (up to 93% ee). Functional groups such as halogen atoms (F, Cl, and Br), thienyl, and silyl moieties are tolerated well.
View Article and Find Full Text PDFHerein, a cobalt-catalyzed intramolecular enantioselective reductive Heck reaction is disclosed. Starting from --iodoaryl-2-(trifluoromethyl)acrylamides, a plethora of chiral oxindoles bearing trifluoromethylated quaternary stereogenic centers at the C3-position are achieved in moderate to good yields (up to 88% yield) and good to excellent enantioselectivities (up to 94% ee) by employing zinc/silane as reducing agent. Other than the trifluoromethyl group, a number of chiral oxindoles bearing alkyl, aryl, and ester groups at C3-position were also obtained albeit in relatively lower enantioselectivities (68-78% ee).
View Article and Find Full Text PDFAn efficient copper-catalyzed dearomative [3 + 2] annulation of indoles with 2-iodoacetic acid is developed. By employing Cu(OTf)/2,2'-bis(2-oxazoline) as the catalyst and LPO as the oxidant, a series of indoline-fused butyrolactones were synthesized in moderate to good yields. The reaction features mild conditions, a broad substrate scope, and readily available starting materials.
View Article and Find Full Text PDFAn enantioselective copper-catalyzed 1,2-arylboration reaction of enamines has been developed by employing ()-xyl-BINAP as a chiral ligand. A number of chiral borate-containing 3,3'-disubstituted isoindolinones were obtained in moderate to good yields and good to excellent enantioselectivities from the reactions of -(-iodobenzoyl)enamines and bis(pinacolato)diboron (Bpin) under mild reaction conditions. Synthetic transformations of the products were conducted to demonstrate the practicality of this reaction.
View Article and Find Full Text PDFAn enantioselective Pd-catalyzed intramolecular desymmetrizing cycloisomerization of -(cyclopent-3-en-1-yl)propiolamides has been developed by employing a new chiral phosphoramidite ligand. A series of structurally unique bridged azabicycles are achieved in moderate to excellent yields with good / selectivity and high enantioselectivity. Synthetic transformations are conducted to demonstrate the practical utility of this reaction.
View Article and Find Full Text PDFAn enantioselective Pd-catalyzed intramolecular dearomative reductive Heck reaction of -(-bromoaryl) indole-3-carboxamide is developed. By employing Pd(dba)/SPINOL-based phosphoramidite as the chiral catalyst and HCONa as the hydride source, a series of enantioenriched spiro indolines bearing vicinal stereocenters were afforded in moderate to good yields with excellent enantioselectivities. The reductive Heck reaction of formal tetrasubstituted alkene bearing β-hydrogens is therefore realized by inhibiting β-H elimination.
View Article and Find Full Text PDFChem Commun (Camb)
April 2024
Herein, we describe a copper-catalyzed intramolecular dearomative amination of indoles a formal aza-Wacker reaction. This protocol provides an efficient method to access aza-polycyclic indoline molecules bearing exocyclic CC bonds in moderate to excellent yields in the presence of molecular oxygen as an oxidant. It is worth noting that indolin-3-ones are achieved when employing C3-non-substituted indoles as substrates.
View Article and Find Full Text PDFA palladium-catalyzed dearomative diarylation of C2-deuterated or C2-nonsubstituted indoles through domino Heck/Suzuki coupling is established. Relying on electron-deficient phosphite ligand, side reactions including intermolecular Suzuki coupling and intramolecular C-D/H arylation are inhibited and a wide range of 2,3-diarylated indolines bearing vicinal tertiary stereocenters including deuterated ones are afforded in moderate to excellent yields (up to 94%) and excellent diastereoselectivities (>20:1). The catalyst loading can be lowered to 0.
View Article and Find Full Text PDF-Sulfonatocalix[]arenes (SCnA) have demonstrated great potential for drug encapsulation through host-guest complexation to improve solubility, stability, and bioavailability. In this study, the solubilization effect of SCnA ( = 4, 6, 8) on 95 active compounds derived from traditional Chinese medicine (TCM) was investigated. Based on the significant solubilization effect on alkaloids, SC6A/SC8A and 76 alkaloids were selected as the host and guest, respectively, to determine the binding constant by competitive fluorescence titration.
View Article and Find Full Text PDFA Pd-catalyzed intramolecular dearomative [4 + 2] cycloaddition reaction of naphthalenes with arylalkynes is developed. The protocol provides a straightforward method to access a range of polycyclic dihydronaphthalenes containing two vicinal all-carbon stereocenters in moderate yields under mild conditions in an air atmosphere. The deuterium labeling experiment suggests a pathway involving electrophilic dearomatization followed by Friedel-Crafts cyclization.
View Article and Find Full Text PDFHerein, we describe a nickel-catalyzed asymmetric dearomative aryl-difluoroallylation reaction of indoles with α-trifluoromethyl alkenes as an electrophilic coupling partner. The reaction proceeds via a cascade sequence involving dearomative Heck cyclization and reductive allylic defluorination. A series of -difluoroallyl substituted indolines are obtained in moderate to good yields (36-77% yield) with excellent enantioselectivity (up to 99% ee).
View Article and Find Full Text PDFA highly enantioselective cobalt-catalyzed desymmetrizing reductive cyclization of alkynyl cyclodiketones has been developed. Under mild reaction conditions by employing HBpin as a reducing agent and ferrocene-based PHOX as a chiral ligand, a series of polycyclic tertiary allylic alcohols bearing contiguous quaternary stereocenters are achieved in moderate to excellent yields with excellent enantioselectivities (up to 99%). Broad substrate scope and high functional group compatibility are observed in this reaction.
View Article and Find Full Text PDFBackground: Cimicifugae Rhizoma, known in Chinese as Shengma, is a common medicinal material in traditional Chinese medicine (TCM), mainly used for treating wind-heat headaches, sore throat, uterine prolapse, and other diseases.
Objectives: An approach using a combination of ultra-performance liquid chromatography (UPLC), MS, and multivariate chemometric methods was designed to assess the quality of Cimicifugae Rhizoma.
Methods: All materials were crushed into powder and the powdered sample was dissolved in 70% aqueous methanol for sonication.
A palladium-catalyzed dearomatizing [2+2+1] spiroannulation of indoles with two molecular internal alkynes is developed in the presence of Cu(OAc)/O as the oxidant, in which a domino sequence including C-H activation of indole followed by consecutive Heck reactions is involved. A range of 3,3'-spiroindolines bearing tetrasubstituted cyclopentadiene moieties and exocyclic C═C bonds at C2 are obtained in moderate to excellent yields.
View Article and Find Full Text PDFIntroduction: Alkaloids exist in various herbal medicine widely and exhibit diverse biological and pharmacological activities. p-Sulphonatocalix[6]arenes (SC6A) and p-sulphonatocalix[8]arenes (SC8A) are water-soluble supramolecular macrocycles and are applied to the extraction of alkaloids from herbal products.
Objective: In this study, an innovative method of SC6A/SC8A assisted extraction of the alkaloids from herbs was established.
Highly enantioselective palladium-catalyzed dearomative reductive Heck reaction and domino Heck-Suzuki reaction of 2-CF-indoles have been developed. Using Pd(OAc)/()-Synphos as the catalyst and EtSiH as a hydride source, a variety of indolines bearing a 2-trifluoromethyl quaternary stereocenter were obtained a dearomative reductive Heck reaction. Alternatively, using Pd(dba)/phosphoramidite as the catalyst and ArBNa as a coupling partner, structurally diverse indolines containing two vicinal carbon stereocenters were afforded through the domino dearomative Heck-Suzuki reaction.
View Article and Find Full Text PDFOlefin functionalization represents one of the most important synthetic transformations in organic synthesis. Over the past decades, palladium-catalyzed enantioselective Heck reactions, and Heck/anion-capture domino sequences through olefin carbopalladation followed by termination of the resulting alkyl-Pd species have been extensively developed. Extension of the coupling partners from classical olefins to other π-components would enable further advances and open new space in this field.
View Article and Find Full Text PDFIntroduction: Folium nelumbinis is used as vegetable, functional food and herbal medicine in Asia. p-Sulfonatocalix[6]arene (SC6A) is a water-soluble supramolecular macrocycle and has never been applied to the extraction of herbal products.
Objective: In this study, SC6A-assisted extraction of nuciferine from Folium nelumbinis has been carried out to develop an eco-friendly extraction process with high extraction efficacy and easy operation.
Enantioselective [3 + 2] annulation of -heteroarenes with alkynes has been developed via a cobalt-catalyzed dearomative umpolung strategy in the presence of chiral ligand and reducing reagent. A variety of electron-deficient -heteroarenes, including quinolines, isoquinolines, quinoxaline, and pyridines, and internal or terminal alkynes are employed in this reaction, showing a broad substrate scope and good functionality tolerance. Annulation of electron-rich indoles with alkynes is also developed.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
March 2021
The extensively developed ene-type enantioselective cycloisomerization of classical 1,n-enynes provides an efficient approach to chiral cyclic 1,4-dienes. In contrast, the catalytic asymmetric heteroarenyne (heteroarene-alkyne) cycloisomerization involving the dearomative transformation of endocyclic aromatic C=C bonds remains unknown. Herein, we communicate a PdH-catalyzed enantioselective heteroarenyne cycloisomerization reaction of alkyne-tethered indole substrates (formal 1,5- and 1,6-enynes).
View Article and Find Full Text PDFDearomative functionalization reactions represent an important strategy for the synthesis of valuable three-dimensional molecules from simple planar aromatics. Naphthalene is a challenging arene towards transition-metal-catalyzed dearomative difunctionalization reactions. Reported herein is an application of naphthalene as a masked conjugated diene in a palladium-catalyzed dearomative 1,4-diarylation or 1,4-vinylarylation reaction via tandem Heck/Suzuki sequence.
View Article and Find Full Text PDFArylboration and arylsilylation reactions of -(2-iodoaryl)acrylamides with bis(pinacolato)-diboron (Bpin) or PhMeSi-Bpin are developed by using simple CuOAc as the sole catalyst. A range of boron- or silane-bearing 3,3'-disubstituted oxindoles are obtained in moderate to excellent yields. The reaction is proposed to proceed via a domino sequence involving intermolecular olefin borylcupration or silylcupration followed by intramolecular coupling of an alkyl-Cu intermediate with aryl iodide.
View Article and Find Full Text PDFA palladium-catalyzed domino Larock annulation/dearomative Heck reaction is developed, which delivers a range of tetracyclic indoline derivatives in moderate to excellent yields through a Larock annulation of N-bromobenzoyl o-iodoanilines with alkynes and a subsequent intramolecular dearomative Heck reaction. This protocol provides a straightforward route to structurally diverse indolines from readily available starting materials by forming two new rings and three chemical bonds in a single step.
View Article and Find Full Text PDFAn efficient palladium-catalyzed intramolecular deacetylative dearomatization reaction of 3-acetoxyindoles has been developed. A range of tetracyclic indolin-3-ones bearing C2-quaternary stereocenters are achieved in good yields, showing a wide substrate scope for this reaction. A preliminary enantioselective reaction is established to furnish the product in 63% ee by using (,,)-phosphoramide-PE as a chiral ligand.
View Article and Find Full Text PDFEnantioselective intramolecular dearomative Heck reactions have been developed by Pd-catalyzed cross-coupling of aryl halides or aryl triflates with the internal C═C bond of indoles, benzofurans, pyrroles, and furans. A variety of structurally unique spiroheterocycles and benzofused heterocycles having N/O-substituted quaternary carbon stereocenters, and exocyclic olefin moieties were afforded in moderate to excellent yields with good to excellent enantioselectivities, showing a broad scope of the present protocol. A series of new BINOL- and H8-BINOL-based phosphoramidite ligands were synthesized and proved to be efficient chiral ligands in the reactions of C2-tethered substrates to form spiroheterocycles.
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