210426-69-0

Upstream product

• 110-52-1 1,4-dibromo-butane 
• 88-05-1 2,4,6-trimethylaniline 

Downstream Products

• 250650-89-6 1-(2,4,6-trimethyl-3-nitro-phenyl)-pyrrolidine 
• 250651-02-6 2,4,6-Trimethyl-3-pyrrolidin-1-yl-phenylamine 

Relevant academic research and scientific papers

Dehydrogenation/(3+2) Cycloaddition of Saturated Aza-Heterocycles via Merging Organic Photoredox and Lewis Acid Catalysis

Herein, we report a photoinduced dehydrogenation/(3+2) cycloaddition reaction by merging organic photoredox and Lewis acid catalysis, providing a straightforward and efficient approach for directly installing a benzofuran skeleton on the saturated aza-heterocycles. In this protocol, we also describe a novel organic photocatalyst (t-Bu-DCQ) with the advantages of a wider redox potential, easy synthesis, and a low price. Furthermore, the stepwise activation mechanism of dual C(sp3)-H bonds was demonstrated by a series of experimental and computational studies.

Organic photoredox catalytic α-C(sp3)-H phosphorylation of saturated: Aza -heterocycles

A metal-free C(sp3)-H phosphorylation of saturated aza-heterocycles via the merger of organic photoredox and Br?nsted acid catalyses was established under mild conditions. This protocol provided straightforward and economic access to a variety of valuable α-phosphoryl cyclic amines by using commercially available diarylphosphine oxide reagents. In addition, the D-A fluorescent molecule DCQ was used for the first time as a photocatalyst and exhibited an excellent photoredox catalytic efficiency in this transformation. A series of mechanistic experiments and DFT calculations demonstrated that this transformation underwent a sequential visible light photoredox catalytic oxidation/nucleophilic addition process.

Organocatalytic Cascade β-Functionalization/Aromatization of Pyrrolidines via Double Hydride Transfer

An unprecedented cascade β-functionalization/aromatization reaction of N-arylpyrrolidines was established. A series of β-substituted arylpyrroles embedded with trifluoromethyl groups are provided directly from N-arylpyrrolidines. The deuterium-labeling experiments indicate that sequential double hydride transfer processes serve as the key steps in this transformation.

Redox-Neutral β-C(sp3)-H Functionalization of Cyclic Amines via Intermolecular Hydride Transfer

Herein, we report the first redox-neutral and transition-metal-free β-C(sp3)-H functionalization of cyclic amines via a consecutive intermolecular hydride transfer process. A series of N-aryl pyrrolidines and N-aryl 1,2,3,4-tetrahydropyridines decorated with CF3 and carboxylic ester functionalities are directly accessed in good yields from pyrrolidines and piperidines. This work pushes forward the application of the intermolecular hydride transfer strategy in one-step assembly of molecular complexity.

C-H Functionalization of Amines via Alkene-Derived Nucleophiles through Cooperative Action of Chiral and Achiral Lewis Acid Catalysts: Applications in Enantioselective Synthesis

Catalytic transformations of α-amino C-H bonds to afford valuable enantiomerically enriched α-substituted amines, entities that are prevalent in pharmaceuticals and bioactive natural products, have been developed. Typically, such processes are carried out

Dual C(sp3)?H Bond Functionalization of N-Heterocycles through Sequential Visible-Light Photocatalyzed Dehydrogenation/[2+2] Cycloaddition Reactions

Herein we describe a mild method for the dual C(sp3)?H bond functionalization of saturated nitrogen-containing heterocycles through a sequential visible-light photocatalyzed dehydrogenation/[2+2] cycloaddition procedure. As a complementary approach to the well-established use of iminium ion and α-amino radical intermediates, the elusive cyclic enamine intermediates were effectively generated by photoredox catalysis under mild conditions and efficiently captured by acetylene esters to form a wide array of bicyclic amino acid derivatives, thus enabling the simultaneous functionalization of two vicinal C(sp3)?H bonds.

Dehydrogenative Aromatization and Sulfonylation of Pyrrolidines: Orthogonal Reactivity in Photoredox Catalysis

Oxidative dehydrogenative aromatization and selective sulfonylation reactions of N-heterocycles under visible-light photoredox catalysis were established. The mild reaction conditions make this approach an appealing and versatile strategy to functionalize/oxidize pyrrolidines whereby arylsulfonyl chlorides were identified to be both catalyst regeneration and sulfonylation reagents.

Diastereoselective tandem addition-cyclization reactions of unsaturated tertiary amines initiated by photochemical electron transfer (PET)

Polycyclic molecules and tetrahydroquinoleines were obtained in a tandem reaction involving the diastereoselective addition of α-aminoalkyl radicals to (5R)-5-menthyloxy-2[5H]-furanone 1. The facial diastereoselectivity on 1 is ≥90%. The α-aminoalkyl radicals were produced from tertiary amines by photochemical-induced electron transfer. When N, N-dialkylanilines 19 were used as starting tertiary amines, a rearomatization step was involved and important side reactions of 1 were observed. A mechanistic study involving isotopic labeling of the starting amine indicated that the byproducts resulted from reduction of I during the rearomatization process. An efficient optimization of the reaction was obtained by simply adding acetone or cyclopentanone as mild oxidants to the reaction mixture. The side products resulting from reduction of the furanone 1 were completely suppressed under these conditions, and the yields of the tetrahydroquinolines 21ai, 22a-f, and 26g-i were doubled.

Endothelin antagonists: Substituted mesitylcarboxamides with high potency and selectivity for ET(A) receptors

We have previously disclosed the discovery of 2,4-disubstituted anilinothiophenesulfonamides with potent ET(A)-selective endothelin receptor antagonism and the subsequent identification of sitaxsentan (TBC11251, 1) as a clinical development compound (Wu et al. J. Med. Chem. 1997, 40, 1682 and 1690). The orally active 1 has demonstrated efficacy in a phase II clinical trial of congestive heart failure (Givertz et al. Circulation 1998, 98, Abstr. 3044) and was active in rat models of myocardial infarction (Podesser et al. Circulation 1998, 98, Abstr. 2896) and acute hypoxia-induced pulmonary hypertension (Chen et al. FASEB J. 1996, 10 (3), A104). We now report that an additional substituent at the 6-position of the anilino ring further increases the potency of this series of compounds. It was also found that a wide range of functionalities at the 3-position of the 2,4,6-trisubstituted ring increased ETA selectivity by ~10-fold while maintaining in vitro potency, therefore rendering the compounds amenable to fine-tuning of pharmacological and toxicological profiles with enhanced selectivity. The optimal compound in this series was found to be TBC2576 (7u), which has ~10- fold higher ETA binding affinity than 1, high ET(A)/ET(B) selectivity, and a serum half-life of 7.3 h in rats, as well as in vivo activity.

A convenient synthesis of hindered N-ARYL substituted cyclic amines

An efficient and high yielding synthesis of N-substituted pyrrolidines and piperidines is described.