939799-25-4

Upstream product

• 3132-99-8 m-bromobenzoic aldehyde 
• 5680-79-5 glycine ethyl ester hydrochloride 

Downstream Products

• 939799-31-2 methyl (1S,3R,3aS,6aR)-4,6-dioxo-3-(m-bromophenyl)-5-phenyl-octahydropyrrolo[3,4-c]pyrrole-1-carboxylate 
• 1420291-83-3 trimethyl (2R,3S,4R,5S)-5-(3-bromophenyl)pyrrolidine-2,3,4-tricarboxylate 

Relevant academic research and scientific papers

Copper(i)/Ganphos catalysis: enantioselective synthesis of diverse spirooxindoles using iminoesters and alkyl substituted methyleneindolinones

A copper-catalyzed asymmetric 1,3-dipolar cycloaddition of glycine iminoesters with alkyl substituted 3-methylene-2-oxindoles is described. By usingde novodesign of P-stereogenic phosphines as ligands, spiro[pyrrolidin-3,3'-oxindole]s are generated in good to excellent yields with high asymmetric induction. A further reduced catalyst loading of 0.1 mol% is sufficient to achieve a satisfactory enantioselectivity of 90% ee. The DFT calculations suggest the second Michael addition of the 1,3-dipole to be the rate- andenantio-determining step. A key feature of this 1,3-dipolar cycloaddition is the wide substrate applicability, even with alkyl aldehyde-derived azomethine ylide; thus it has streamlined a highly enantioselective access to a new class of antiproliferative agents, MDM2-p53.

Well-Designed Phosphine-Urea Ligand for Highly Diastereo- and Enantioselective 1,3-Dipolar Cycloaddition of Methacrylonitrile: A Combined Experimental and Theoretical Study

A novel chiral phosphine-urea bifunctional ligand has been developed for Cu-catalyzed asymmetric 1,3-dipolar cycloaddition of iminoesters with methacrylonitrile, a long-standing challenging substrate in asymmetric catalysis. Distortion-interaction energy analysis based on density functional theory (DFT) calculations reveals that the distortion energy plays an important role in the observed enantioselectivity, which can be attributed to the steric effect between the phosphine ligand and the dipole reactant. DFT calculations also indicate that nucleophilic addition is the enantioselectivity-determining step and hydrogen bonding between the urea moiety and methacrylonitrile assists in control of the diastereo- and enantioselectivity. By a combination of metal catalysis and organocatalysis, excellent diastereo- and enantioselectivities (up to 99:1 diastereomeric ratio, 99% enantiomeric excess) as well as good yields are achieved. A wide range of substitution patterns of both iminoester and acrylonitrile is tolerated by this catalyst system, providing access to a series of highly substituted chiral cyanopyrrolidines with up to two quaternary stereogenic centers. The synthetic utility is demonstrated by enantioselective synthesis of antitumor agent ETP69 with a pivotal nitrile pharmacophore and an all-carbon quaternary stereogenic center.

Enantioselective Mannich Reaction of Glycine Iminoesters with N-Phosphinoyl Imines: A Bifunctional Approach

A bifunctional catalytic approach for the asymmetric Mannich reaction of glycine iminoesters with N-phosphinoyl imines has been developed. By the combination of metal catalysis and organocatalysis, the vicinal two stereogenic centers were efficiently constructed, affording a wide range of syn-diamino esters in high yields with excellent enantio- and diastereoselectivities (up to >99:1 dr, 99% ee).

Ligand-Controlled Inversion of Diastereo- and Enantioselectivity in Silver-Catalyzed Azomethine Ylide-Imine Cycloaddition of Glycine Aldimino Esters with Imines

A highly diastereo- and enantioselective silver-catalyzed azomethine ylide-imine (AYI) cycloaddition reaction of glycine aldimino esters with imines was developed in which the Xing-Phos-controlled syn-selective or DTBM-Segphos-induced anti-selective AYI cycloaddition reaction could be applied to the synthesis of a variety of stereodivergent 1-alkyl-2,5-substituted imidazolidines with high yields and excellent enantioselectivities (up to 99% ee) as well as good diastereoselectivities (up to 99:1 dr) under mild reaction conditions.

Silicon-based Bulky Group?Tuned Parallel Kinetic Resolution in Copper-Catalyzed 1,3-Dipolar Additions

The development of new strategies or reaction processes that tease new reactivity of functional groups continues to spur synthetic chemists toward innovative solutions that access new compounds. Herein, we find that the silicon-based bulky group enables a 1,3-dipolar addition?initiated parallel kinetic resolution (PKR) to occur unexpectedly, leading to the highly enantioselective synthesis of two structurally different types of amino acid derivatives via chemodivergent [3+2] cycloaddition reactions and tandem conjugate addition-elimination reaction respectively. The resulting and structurally divergent enantioenriched amino acid derivatives that contain four contiguous stereogenic centers and an all-carbon quaternary center were obtained with up to 99% ee with >95:1 dr and good yields. (Figure presented.).

Cycloaddition reactions of glycine imine anions to phenylazocarboxylic esters - A new access to 1,3,5-trisubstituted 1,2,4-triazoles

Phenylazocarboxylic tert-butyl esters have recently been shown to be highly versatile building blocks due to their ability to undergo nucleophilic aromatic substitutions under mild conditions, particularly well with [18F]fluoride, and to act as precursors for aryl radicals. In this article, we now report first examples for cycloaddition reactions to phenylazocarboxylates. In a one-pot reaction with readily accessible glycine imines, a variety of highly substituted 1,2,4-triazoles could be obtained.

Asymmetric [3+2] cycloaddition of azomethine ylides catalyzed by silver(I) triflate with a chiral bipyrrolidine-derived phosphine ligand

Two novel chiral bipyrrolidine-derived phosphine ligands L1 and L2 were synthesized. The AgOTf + L1 protocol catalyzes the asymmetric [3+2] cycloaddition of azomethine ylides with alkenes to give highly substituted pyrrolidines in good yields (up to 90%) with moderate to high diastereoselectivities (up to >19:1 dr) and enantioselectivities (up to 76%).

Asymmetric [3+2] cycloaddition of azomethine ylides catalyzed by silver(I) triflate with a chiral bipyrrolidine-derived phosphine ligand

Two novel chiral bipyrrolidine-derived phosphine ligands L1 and L2 were synthesized. The AgOTf + L1 protocol catalyzes the asymmetric [3+2] cycloaddition of azomethine ylides with alkenes to give highly substituted pyrrolidines in good yields (up to 90%) with moderate to high diastereoselectivities (up to >19:1 dr) and enantioselectivities (up to 76%). Georg Thieme Verlag Stuttgart.New York.

Metal-free asymmetric 1,3-dipolar cycloaddition of N-arylmaleimides to azomethine ylides catalyzed by chiral tertiary amine thiourea

The first metal-free asymmetric 1,3-dipolar cycloaddition of N-arylmaleimides to azomethine ylides catalyzed by chiral tertiary amine thiourea to form multiply substituted pyrrolidines in excellent yields (up to 89%) and enantioselectivities (up to 96% ee) is presented. This procedure allows a rapid diversity-oriented synthesis of chiral pyrrolidine derivatives with high optical purity. A series of bifunctional thiourea catalysts were applied for the first time to the highly asymmetric 1,3-dipolar cycloaddition of N-arylmaleimides to azomethine ylides togive the products in excellent yields (up to 89%) and enantioselectivities (up to 96% ee).