39769-08-9

Upstream product

• 459-57-4 4-fluorobenzaldehyde 
• 104-94-9 4-methoxy-aniline 
• 67-56-1 methanol 
• 62-53-3 aniline 
• 140-75-0 para-fluorobenzylamine 
• 459-56-3 4-fluorobenzylic alcohol 
• 7292-73-1 (2RS)-N-(p-fluorophenyl)glycine 
• 356531-43-6 4-fluoro-N-(4-methoxyphenyl)benzenemethanamine 
• 405-99-2 para-fluorostyrene 
• 100-17-4 para-methoxynitrobenzene 
• 140373-17-7 α-hydroxymethyl-4-fluorobenzylamine 
• 38693-94-6 (E)-4-<2-(4-fluorophenyl)ethenyl>phenol 
• 2101-87-3 p-methoxy-phenylazide 

Downstream Products

• 144465-79-2 (3R,4S)-1-(4-methoxyphenyl)-3-(triisopropylsilyloxy)-4-(4-fluorophenyl)azetidin-2-one 
• 172851-54-6 (3R,4S)-3-hydroxy-4-(4-fluorophenyl)azetidin-2-one 
• 172851-37-5 (3R,4S)-3-(triisopropylsilyloxy)-4-(4-fluorophenyl)azetidin-2-one 
• 172851-39-7 (3R,4S)-1-tert-butoxycarbonyl-3-(1-triisopropysilyloxy)-4-(4-fluorophenyl)azetidin-2-one 
• 172851-40-0 (3R,4S)-1-(4-fluorobenzoyl)-3-triisopropysilyloxy-4-(4-fluorophenyl)azetidin-2-one 

Relevant academic research and scientific papers

Azetidinimines as a novel series of non-covalent broad-spectrum inhibitors of β-lactamases with submicromolar activities against carbapenemases KPC-2 (class A), NDM-1 (class B) and OXA-48 (class D)

The occurrence of resistances in Gram negative bacteria is steadily increasing to reach extremely worrying levels and one of the main causes of resistance is the massive spread of very efficient β-lactamases which render most β-lactam antibiotics useless. Herein, we report the development of a series of imino-analogues of β-lactams (namely azetidinimines) as efficient non-covalent inhibitors of β-lactamases. Despite the structural and mechanistic differences between serine-β-lactamases KPC-2 and OXA-48 and metallo-β-lactamase NDM-1, all three enzymes can be inhibited at a submicromolar level by compound 7dfm, which can also repotentiate imipenem against a resistant strain of Escherichia coli expressing NDM-1. We show that 7dfm can efficiently inhibit not only the three main clinically-relevant carbapenemases of Ambler classes A (KPC-2), B (NDM-1) and D (OXA-48) with Ki's below 0.3 μM, but also the cephalosporinase CMY-2 (class C, 86% inhibition at 10 μM). Our results pave the way for the development of a new structurally original family of non-covalent broad-spectrum inhibitors of β-lactamases.

Au(I) Catalyzed Synthesis of Densely Substituted Pyrazolines and Dihydropyridines via Sequential Aza-Enyne Metathesis/6π-Electrocyclization

A gold(I) autotandem catalysis protocol is reported for the de novo synthesis of densely substituted pyrazolines and dihydropyridines from the corresponding imine derivatives in a highly regioselective fashion via a one-pot aza-enyne metathesis/6π-electrocyclization sequence. The substituents on the nitrogen atom of the imine perfectly control the reaction pathways from the pivotal 1-azabutadiene intermediate; thus, carbazates were converted into pyrazolines via 6π-electrocyclization of α,β-unsaturated hydrazones, while aryl imines provided dihydropyridines via 6π-electrocyclization of 3-azahexatrienes.

Iron-Catalyzed Hydrogen Transfer Reduction of Nitroarenes with Alcohols: Synthesis of Imines and Aza Heterocycles

A straightforward and selective reduction of nitroarenes with various alcohols was efficiently developed using an iron catalyst via a hydrogen transfer methodology. This protocol led specifically to imines in 30-91% yields, with a good functional group tolerance. Noticeably, starting from o-nitroaniline derivatives, in the presence of alcohols, benzimidazoles can be obtained in 64-72% yields when the reaction was performed with an additional oxidant, DDQ, and quinoxalines were prepared from 1,2-diols in 28-96% yields. This methodology, unprecedented at iron for imines, also provides a sustainable alternative for the preparation of quinoxalines and benzimidazoles.

Dearomative Photocatalytic Construction of Bridged 1,3-Diazepanes

The construction of diverse sp3-rich skeletal ring systems is of importance to drug discovery programmes and natural product synthesis. Herein, we report the photocatalytic construction of 2,7-diazabicyclo[3.2.1]octanes (bridged 1,3-diazepanes) via a reductive diversion of the Minisci reaction. The fused tricyclic product is proposed to form via radical addition to the C4 position of 4-substituted quinoline substrates, with subsequent Hantzsch ester-promoted reduction to a dihydropyridine intermediate which undergoes in situ two-electron ring closure to form the bridged diazepane architecture. A wide scope of N-arylimine and quinoline derivatives was demonstrated and good efficiency was observed in the construction of sterically congested all-carbon quaternary centers. Computational and experimental mechanistic studies provided insights into the reaction mechanism and observed regioselectivity/diastereoselectivity.

Diethylsilane as a Powerful Reagent in Au Nanoparticle-Catalyzed Reductive Transformations

Diethylsilane (Et2SiH2), a simple and readily available dihydrosilane, that exhibits superior reactivity, as compared to monohydrosilanes, in a series of reductive transformations catalyzed by recyclable and reusable Au nanoparticles (1 mol-%) supported on TiO2. It reduces aldehydes or ketones almost instantaneously at ambient conditions. It can be used in a one pot rapid reductive amination procedure, in which premixing of aldehyde and amine is required prior to the addition of the reducing agent and the catalyst, even in a protic solvent. An unprecedented method for the synthesis of N-arylisoindolines is also shown in the reductive amination between o-phthalaldehyde and anilines. In this transformation, it is proposed that the intermediate N,2-diphenylisoindolin-1-imines are reduced stepwise to the isoindolines. Finally, Et2SiH2 readily reduces amides into amines in excellent yields and shorter reaction times relative to previously known analogous nano Au(0)-catalyzed protocols.

Ni-Catalyzed asymmetric reduction of α-keto-β-lactams: via DKR enabled by proton shuttling

Chiral α-hydroxy-β-lactams are key fragments of many bioactive compounds and antibiotics, and the development of efficient synthetic methods for these compounds is of great value. The highly enantioselective dynamic kinetic resolution (DKR) of α-keto-β-lactams was realized via a novel proton shuttling strategy. A wide range of α-keto-β-lactams were reduced efficiently and enantioselectively by Ni-catalyzed asymmetric hydrogenation, providing the corresponding α-hydroxy-β-lactam derivatives with high yields and enantioselectivities (up to 92% yield, up to 94% ee). Deuterium-labelling experiments indicate that phenylphosphinic acid plays a pivotal role in the DKR of α-keto-β-lactams by promoting the enolization process. The synthetic potential of this protocol was demonstrated by its application in the synthesis of a key intermediate of Taxol and (+)-epi-Cytoxazone. This journal is

Iron-Catalyzed Nitrene Transfer Reaction of 4-Hydroxystilbenes with Aryl Azides: Synthesis of Imines via C=C Bond Cleavage

C=C bond breaking to access the C=N bond remains an underdeveloped area. A new protocol for C=C bond cleavage of alkenes under nonoxidative conditions to produce imines via an iron-catalyzed nitrene transfer reaction of 4-hydroxystilbenes with aryl azides is reported. The success of various sequential one-pot reactions reveals that the good compatibility of this method makes it very attractive for synthetic applications. On the basis of experimental observations, a plausible reaction mechanism is also proposed.

Visible-Light-Mediated, Chemo- and Stereoselective Radical Process for the Synthesis of C-Glycoamino Acids

An approach for efficient synthesis of C-glycosyl amino acids is described. Different from typical photoredox-catalyzed reactions of imines, the new process follows a pathway in which α-imino esters serve as electrophiles in chemoselective addition reactions with nucleophilic glycosyl radicals. The process is highlighted by the mild nature of the reaction conditions, the highly stereoselectivity attending C-C bond formation, and its applicability to C-glycosylations using both armed and disarmed pentose and hexose derivatives.

Cobalt-Catalyzed Dehydrogenative Coupling of Amines into Imines

Primary amines have been subjected to an acceptorless dehydrogenative homo- and heterocoupling into imines with a cobalt catalyst. The catalytically active species are composed of cobalt nanoparticles, which are generated in situ by heating Co2(CO)8 in the presence of trioctylphosphine oxide as a surfactant. The nanoparticles have been characterized by transmission electron microscopy where the image showed spherical and small particles with a narrow size distribution. The catalyst can be recovered and used again with essentially no effect on the yield. The catalyst can also be used for the dehydrogenative coupling of alcohols and amines into imines.

Rhodium-catalyzed synthesis of imines and esters from benzyl alcohols and nitroarenes: Change in catalyst reactivity depending on the presence or absence of the phosphine ligand

The [Rh(COD)Cl]2/xantphos/Cs2CO3 system efficiently catalyzes the reductive N-alkylation of aryl nitro compounds with alcohols by a borrowing-hydrogen strategy to afford the corresponding imine products in good to excellent yields. In the absence of xantphos, the [Rh(COD)Cl]2/Cs2CO3 catalytic system behaves as an effective catalyst for the dehydrogenative coupling of alcohols to esters, with nitrobenzene as a hydrogen acceptor. The reactivity of the rhodium catalytic system can be easily manipulated to selectively afford the imine or ester.