Showing papers by "Xiaohua Liu published in 2015"

Asymmetric Dearomatization of Indoles through a Michael/Friedel–Crafts‐Type Cascade To Construct Polycyclic Spiroindolines

Abstract: A highly efficient asymmetric dearomatization of indoles was realized through a cascade reaction between 2-isocyanoethylindole and alkylidene malonates catalyzed by a chiral N,N'-dioxide/Mg(II) catalyst. Fused polycyclic indolines containing three stereocenters were afforded in good yields with excellent diastereo- and enantioselectivities through a Michael/Friedel-Crafts/Mannich cascade. When 2-substituted 2-isocyanoethylindoles were used, spiroindoline derivatives were obtained through a Michael/Friedel-Crafts reaction.

Regio- and Enantioselective Aza-Diels–Alder Reactions of 3-Vinylindoles: A Concise Synthesis of the Antimalarial Spiroindolone NITD609

Abstract: An asymmetric aza-Diels-Alder reaction of 3-vinylindoles with isatin-derived ketimines has been developed. A series of spiroindolone derivatives were thus obtained in good to excellent yields with excellent enantioselectivity (up to 96 % yield and 99 % ee). Furthermore, the antimalarial compound NITD609 could be obtained in three steps with an overall yield of 40.6 %. Control experiments and operando IR experiments imply a concerted reaction pathway. The regioselectivity and exo selectivity result from π-π interactions between the two indoline rings of the two reactants.

Asymmetric synthesis of 2,3-dihydropyrroles by ring-opening/cyclization of cyclopropyl ketones using primary amines.

Abstract: The asymmetric ring-opening/cyclization of cyclopropyl ketones with primary amine nucleophiles was catalyzed by a chiral N,N′-dioxide/scandium(III) complex through a kinetic resolution process. A broad range of cyclopropyl ketones and primary amines are suitable substrates of this reaction. The corresponding products were afforded in excellent enantioselectivities and yields (up to 97 % ee and 98 % yield) under mild reaction conditions. This method provides a promising access to chiral 2,3-dihydropyrroles as well as an effective procedure for the kinetic resolution of 2-substituted cyclopropyl ketones.

Enantioselective Construction of Vicinal Tetrasubstituted Stereocenters by the Mannich Reaction of Silyl Ketene Imines with Isatin‐Derived Ketimines

Abstract: A highly enantioselective Mannich reaction of silyl ketene imines with isatin-derived ketimines has been realized by using a chiral N,N'-dioxide/Zn(II) catalyst. A variety of β-amino nitriles containing congested vicinal tetrasubstituted stereocenters were obtained with excellent outcomes (up to 98 % yield, >19:1 d.r. and 99 % ee). Based on the experimental investigations, a possible transition state has been proposed to explain the origin of the asymmetric induction.

Direct Synthesis of Chiral Allenoates from the Asymmetric C-H Insertion of α-Diazoesters into Terminal Alkynes.

Abstract: The asymmetric C-H insertion of α-diazoesters into 1-alkynes was achieved using chiral cationic guanidinium salts and copper(I) complexes. Optically active 2,4-disubstituted allenoates were generated under mild reaction conditions from various α-diazoesters and 1-alkynes in high yield (up to 99%) and enantioselectivity (up to 97:3 e.r.). Control experiments excluded the possibility of an asymmetric isomerization of alkynoates.

Chiral Bifunctional Guanidine-Catalyzed Enantioselective Aza-Henry Reaction of Isatin-Derived Ketimines

Abstract: An efficient asymmetric aza-Henry reaction of isatin-derived ketimines has been achieved by using a chiral guanidine–amide organocatalyst. A series of 3-substituted 3-amino-2-oxindoles was obtained with excellent results (up to 99% yield, 94% ee). Other functionalized derivatives were also conveniently transformed. This metal-free system was convenient, practical, and insensitive to air and moisture. On the basis of the crystal structure of the catalyst and NMR spectra analysis, a bifunctional catalytic model was suggested to explain the origin of the asymmetric process.

Catalytic Asymmetric Intramolecular Homologation of Ketones with α-Diazoesters: Synthesis of Cyclic α-Aryl/Alkyl β-Ketoesters

Abstract: A catalytic asymmetric intramolecular homologation of simple ketones with α-diazoesters was firstly accomplished with a chiral N,N′-dioxide–Sc(OTf)3 complex. This method provides an efficient access to chiral cyclic α-aryl/alkyl β-ketoesters containing an all-carbon quaternary stereocenter. Under mild conditions, a variety of aryl- and alkyl-substituted ketone groups reacted with α-diazoester groups smoothly through an intramolecular addition/rearrangement process, producing the β-ketoesters in high yield and enantiomeric excess.

Ligand Control of Diastereodivergency in Asymmetric Inverse Electron Demand Diels–Alder Reaction

Abstract: A diastereodivergent direct catalytic asymmetric inverse electron demand Diels–Alder reaction between ketenes and 3-alkylenyloxindoles was accomplished by using chiral N,N′-dioxide/gadolinium complexes. By adjusting only the substituents of the ligand and retaining other catalysis conditions, both syn- and anti-indole-fused dihydropyranones bearing two vicinal stereogenic centers were obtained in high yields with excellent ee values. Thus, by changing the configuration of the chiral ligands, all stereoisomers could be obtained from the same set of starting materials.

Asymmetric Synthesis of 2,3‐Dihydropyrroles by Ring‐Opening/Cyclization of Cyclopropyl Ketones Using Primary Amines.

Abstract: The asymmetric ring-opening/cyclization of cyclopropyl ketones with primary amine nucleophiles is catalyzed by a chiral N,N′-dioxide/scandium(III) complex through a kinetic resolution process.

Method for asymmetric catalytic synthesis of gamma-nitropyrazole amide compound

Abstract: The invention relates to a method for asymmetric catalytic synthesis of a gamma-nitropyrazole amide compound. The method comprises the following steps: reacting at the temperature of 30 DEG C and at the normal pressure for 72-96h by taking nitroparaffin and alpha, beta-unsaturated pyrazole amide as raw materials, taking a complex formed by chiral amine oxide and a rare earth metal compound as a catalyst, taking a molecular sieve shown in the specification as an additive and taking dichloromethane as a solvent to obtain the chiral gamma-nitropyrazole amide compound, wherein the yield is up to 99% and the enantiomeric excess is up to 99% ee. The catalytic system has the advantages of simplicity in operation, mild reaction conditions, no need of using acid and base additives, convenience in purification of a product, high yield and enantioselectivity, an effect of being in line with green atom economy and good industrial application prospects; furthermore, the gamma-nitropyrazole amide compound obtained by reaction can obtain some molecules with physiological activity by simple chemical conversions.

Method for asymmetric catalytic synthesis of spirocyclic tetrahydrocarbazoline compound

Abstract: The invention discloses a method for asymmetric catalytic synthesis of a spirocyclic tetrahydrocarbazoline compound, comprising the steps: by taking 3-alkenyl indole and isatin derived ketimine as raw materials, a complex formed by chiral amine oxide and nickel trifluoromethane sulfonate as a catalyst and dichloromethane as a solvent, performing reaction on the raw materials at (-30) DEG C to (-10) DEG C at the normal pressure for 96-192h; then adding 6.0M HCl(solution) and performing reaction at 30 DEG C for 4-48h to obtain the chiral spirocyclic tetrahydro carbazoline compound, wherein the yield of the chiral spirocyclic tetrahydro carbazoline compound can reach up to 95%, and the enantioselectivity can reach up to 99%. According to the method provided by the invention, the catalytic reaction conforms with the green chemistry atom economy and has a good prospect in industrial application, thereby providing a new path for asymmetric synthesis of compounds with high anti-malarial activity (NITD609).

Nickel(II)‐Catalyzed Asymmetric Propargyl and Allyl Claisen Rearrangements to Allenyl‐ and Allyl‐Substituted β‐Ketoesters.

Abstract: This is a highly efficient Ni(II)-catalyzed Claisen rearrangement of a variety of both propargyl and allyl vinyl ethers using a chiral N,N-dioxide as ligand.

Chiral Bifunctional Guanidine-Catalyzed Enantioselective Aza-Henry Reaction of Isatin-Derived Ketimines.

Abstract: An efficient asymmetric aza-Henry reaction of isatin-derived ketimines has been achieved by using a chiral guanidine–amide organocatalyst. A series of 3-substituted 3-amino-2-oxindoles was obtained with excellent results (up to 99% yield, 94% ee). Other functionalized derivatives were also conveniently transformed. This metal-free system was convenient, practical, and insensitive to air and moisture. On the basis of the crystal structure of the catalyst and NMR spectra analysis, a bifunctional catalytic model was suggested to explain the origin of the asymmetric process.

Catalytic Asymmetric Intramolecular Homologation of Ketones with α-Diazoesters: Synthesis of Cyclic α-Aryl/Alkyl β-Ketoesters.

Abstract: A catalytic asymmetric intramolecular homologation of simple ketones with α-diazoesters was firstly accomplished with a chiral N,N′-dioxide–Sc(OTf)3 complex. This method provides an efficient access to chiral cyclic α-aryl/alkyl β-ketoesters containing an all-carbon quaternary stereocenter. Under mild conditions, a variety of aryl- and alkyl-substituted ketone groups reacted with α-diazoester groups smoothly through an intramolecular addition/rearrangement process, producing the β-ketoesters in high yield and enantiomeric excess.

Asymmetric Dearomatization of Indoles Through a Michael/Friedel—Crafts-Type Cascade to Construct Polycyclic Spiroindolines.

Abstract: Asymmetric dearomatization of indoles is achieved by a cascade reaction between isocyanoethylindole and alkylidene malonates catalyzed by a chiral N,N-dioxide/Mg catalyst.

Intermediate for use in synthesizing paroxetine, preparation method for the intermediate, and uses thereof

Abstract: A paroxetine intermediate, a method for preparing the same, and uses thereof are provided. Specifically, the method includes: reacting a compound of formula I below with a compound of formula II in the presence of an organic base under the catalysis of a complex formed from a chiral amine oxide L and a rare-earth metal compound Ln(OTf) 3 to prepare a compound of formula III below: wherein R 1 is alkyl, phenyl or benzyl; R 2 , R 3 , R 4 are each independently C 1 -C 6 alkyl or C 6 -C 10 aryl; the chiral amine oxide L has the following structure: wherein n = 1,2; and R = Ph-, 2,6-Me 2 C 6 H 3 -, 2,6-Et 2 C 6 H 3 -, 2,6-iPr 2 C 6 H 3 -, Ph 2 CH-.

Enantioselective Construction of Vicinal Tetrasubstituted Stereocenters by the Mannich Reaction of Silyl Ketene Imines with Isatin‐Derived Ketimines.

Abstract: A highly enantioselective Mannich reaction of silyl ketene imines with isatin-derived ketimines is realized by using a chiral N,N′-dioxide/ZnII catalyst.

Direct Synthesis of Chiral Allenoates from the Asymmetric C—H Insertion of α‐Diazoesters into Terminal Alkynes.

Abstract: The asymmetric C-H insertion of α-diazoesters into 1-alkynes was achieved using chiral cationic guanidinium salts and copper(I) complexes. Optically active 2,4-disubstituted allenoates were generated under mild reaction conditions from various α-diazoesters and 1-alkynes in high yield (up to 99%) and enantioselectivity (up to 97:3 e.r.). Control experiments excluded the possibility of an asymmetric isomerization of alkynoates.