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Intramolecular amination of organoboronates occurs with a 1,2-metalate shift of an aminoboron "ate" complex to form azetidines, pyrrolidines, and piperidines. Bis(boronates) undergo site-selective amination to form boronate-containing azacycles. Enantiomerically enriched azacycles are formed with high stereospecificity.

In this paper is described an easily synthesized chiral diazaborolidine that is inexpensive, stable, and provides excellent stereoselection across a number of reaction classes. These versatile compounds possess utility in four different classes of cycloaddition reactions, offering good yield and stereoselectivity. X-ray structure analysis provides insight about the origin of stereocontrol.

A diaryl ketone series was identified as vanin-1 inhibitors from a high-throughput screening campaign. While this novel scaffold provided valuable probe

The Pt-catalyzed diboration of cyclic alkenes is extended to unsaturated heterocycles and bicyclic compounds and can be accomplished in a diastereoselective fashion. The optimal procedures, substrate scope, and diastereoselectivity were investigated, and examples employing both homogeneous and heterogeneous catalysis were examined. Lastly, application to the construction of the nucleoside analog (±)-aristeromycin was conducted.

Many diseases are believed to be driven by pathological levels of reactive oxygen species (ROS) and oxidative stress has long been recognized as a driver for inflammatory disorders. Apoptosis signal-regulating kinase 1 (ASK1) has been reported to be activated by intracellular ROS and its inhibition leads to a down regulation of p38-and JNK-dependent signaling. Consequently, ASK1 inhibitors may have the potential to treat clinically important inflammatory pathologies including renal, pulmonary and liver diseases. Analysis of the ASK1 ATP-binding site suggested that Gln756, an amino acid that rarely occurs at the GK+2 position, offered opportunities for achieving kinase selectivity for ASK1 which was applied to the design of a parallel medicinal chemistry library that afforded inhibitors of ASK1 with nanomolar potency and excellent kinome selectivity. A focused optimization strategy utilizing structure-based design resulted in the identification of ASK1 inhibitors with low nanomolar potency in a cellular assay, high selectivity when tested against kinase and broad pharmacology screening panels, and attractive physicochemical properties. The compounds we describe are attractive tool compounds to inform the therapeutic potential of ASK1 inhibition.

A stereoselective synthesis of trans-1,2,3,6-tetrahydropyridines 8 is described. This synthesis proceeds via intramolecular Mistunobu reactions of 1,5-syn-(Z)-amino alcohols 7, which were prepared by a highly diastereo- and enantioselective double-allylboration reaction of aldehyde 5 and silylimine 6. The chiral bifunctional γ-borylallylborane 9E was generated in situ by hydroboration of allene 3 with (diisopinocampheyl)borane 4. This strategy was applied to the total synthesis of andrachcine 1, thus establishing with certainty the absolute and relative configuration of the natural product.

A versatile synthesis of 7-azaindoles from substituted 2-fluoropyridines is described. C3-metalation and 1,4-addition to nitroolefins provide substituted 2-fluoro-3-(2-nitroethyl)pyridines. A facile oxidative Nef reaction/reductive amination/intramolecular SNAr sequence furnishes 7-azaindolines. Finally, optional regioselective electrophilic C5-substitution (e.g., bromination or nitration) and subsequent in situ oxidation delivers highly functionalized 7-azaindoles in high overall efficiency.

A visible-light-driven Minisci protocol that employs an inexpensive earth-abundant metal catalyst, decacarbonyldimanganese Mn2 (CO)10 , to generate alkyl radicals from alkyl iodides has been developed. This Minisci protocol is compatible with a wide array of sensitive functional groups, including oxetanes, sugar moieties, azetidines, tert-butyl carbamates (Boc-group), cyclobutanes, and spirocycles. The robustness of this protocol is demonstrated on the late-stage functionalization of complex nitrogen-containing drugs. Photophysical and DFT studies indicate a light-initiated chain reaction mechanism propagated by . Mn(CO)5 . The rate-limiting step is the iodine abstraction from an alkyl iodide by . Mn(CO)5 .

On all fours: The title reaction with (Ipc)2 BH provides tetrasubstituted enolborinates which undergo aldol reactions with aldehydes to form products with all-carbon quaternary centers with exceptional diastereo- and enantioselectivity. A change to the substitution pattern of the starting amide leads to either diastereomer of the α-methyl-α-ethyl-β-hydroxy carboxamide (1 or 2).

An efficient and highly enantio- and diastereoselective synthesis of syn propionamide aldols is described. Formation of the Z-enolborinate via the hydroboration of 4-acryloylmorpholine with (diisopinocampheyl)borane followed by aldol reactions with representative achiral and chiral aldehydes provided syn-α-methyl-β-hydroxy morpholine carboxamides with excellent enantio- and diastereoselectivity (96–98% ee and d.r. >20:1).

A metal-free and completely regioselective three-component synthesis of highly functionalized pyridines from 1,3-dicarbonyl derivatives and Michael acceptors has been achieved. Activated Michael acceptors, that is, β,γ-unsaturated α-oxo carbonyl derivatives, were utilized, allowing substitution at the 4-position and remarkable functional diversity at the 2-position of the pyridine ring. The scope and limitations of this environmentally friendly domino reaction are disclosed, with full experimental data, and the results of mechanistic investigations are discussed.

The article discusses the preparation of (2R, 3S)-3-Hydroxy-2-methyl-1-morpholino-5-phenylpentan-1-one. Enantioselective reductive aldol reactions that have been developed to date use chiral transition metal catalysts, turnover numbers are modest (typically

The reaction has a vast substrate scope and tolerates multiple functional groups, thus allowing for the diversification of complex biomolecules and active pharmaceutical agents.

A versatile synthesis of 7-azaindoles from substituted 2-fluoropyridines is described. C3-metalation and 1,4-addition to nitroolefins provide substituted 2-fluoro-3-(2-nitroethyl)pyridines. A facile oxidative Nef reaction/reductive amination/intramolecular SNAr sequence furnishes 7-azaindolines. Finally, optional regioselective electrophilic C5-substitution (e.g., bromination or nitration) and subsequent in situ oxidation delivers highly functionalized 7-azaindoles in high overall efficiency.

International audience; We designed a new, user-friendly oxidative dual heterogeneous catalytic system capable of promoting polysubstituted pyridines as unique products from simple activated Michael acceptors, 1,3-dicarbonyls and ammonium acetate. This metal-free environmentally-respectful and totally regioselective domino reaction proved to be a great strategy to access bi- and tri-aryl type pyridines as well as challenging bi- and tri-heteroaryl type pyridines in a single operation.

A nontoxic and inexpensive photocatalytic initiation of anti-Markovnikov hydrothiolation of olefins using visible light is reported. This method is characterized by low catalyst loading, thereby enabling a mild and selective method for radical initiation in thiol–ene reactions between a wide scope of olefins and thiols.

The aldol reaction of stereodefined tetrasubstituted enolborinates, derived from the reaction of α,β-unsaturated carboxamides with enantiopure diisopinocampheylborane, with aliphatic and aromatic aldehydes is described.

An efficient and highly enantio- and diastereoselective synthesis of syn propionamide aldols is described. Formation of the Z-enolborinate via the hydroboration of 4-acryloylmorpholine with (diisopinocampheyl)borane followed by aldol reactions with representative achiral and chiral aldehydes provided syn-α-methyl-β-hydroxy morpholine carboxamides with excellent enantio- and diastereoselectivity (96–98% ee and d.r. >20:1).

The (diisopinocampheyl)borane promoted reductive aldol reaction of acrylate esters 4 is described. Isomerization of the kinetically formed Z(O)-enolborinate 5Z to the thermodynamic E(O)-enolborinate 5E via 1,3-boratropic shifts, followed by treatment with representative achiral aldehydes, leads to anti-α-methyl-β-hydroxy esters 9 or 10 with excellent diastereo- (up to ≥20:1 dr) and enantioselectivity (up to 87% ee). The results of double asymmetric reactions of 5E with several chiral aldehydes are also presented.

A metal-free and completely regioselective three-component synthesis of highly functionalized pyridines from 1,3-dicarbonyl derivatives and Michael acceptors has been achieved. Activated Michael acceptors, that is, β,γ-unsaturated α-oxo carbonyl derivatives, were utilized, allowing substitution at the 4-position and remarkable functional diversity at the 2-position of the pyridine ring. The scope and limitations of this environmentally friendly domino reaction are disclosed, with full experimental data, and the results of mechanistic investigations are discussed.

The (diisopinocampheyl)borane promoted reductive aldol reaction of acrylate esters 4 is described. Isomerization of the kinetically formed Z(O)-enolborinate 5Z to the thermodynamic E(O)-enolborinate 5E via 1,3-boratropic shifts, followed by treatment with representative achiral aldehydes, leads to anti-α-methyl-β-hydroxy esters 9 or 10 with excellent diastereo- (up to ≥20:1 dr) and enantioselectivity (up to 87% ee). The results of double asymmetric reactions of 5E with several chiral aldehydes are also presented.

The reaction of activated Michael acceptors, 1,3-dicarbonyl derivatives and ammonium acetate allows for the preparation of a library of highly substituted bi- and tri(hetero)aryl pyridines.

An unprecedented formal [3 + 3]-cyclodehydration approach leads to the synthesis of N-alkyl and N-arylsubstituted 2-pyridones from β-ketoamides and primary or secondary propargylic alcohols.

International audience; A direct, one-pot and regioselective access to N-alkyl- and N-aryl-substituted 2-pyridones is described from readily available β-ketoamides and either primary or secondary propargyl alcohols. This approach involves the combination of two different cooperative homogeneous and heterogeneous catalytic systems based on a transition metal oxide and a supported organocatalyst, respectively.

In the context of sustainable chemistry, because of economic and ecological increasing pressure, domino multicomponent reactions (MCRs) constitute a central academic and industrial investigation domain in diversity-oriented synthesis of functionalized heterocycles. Although isocyanide-based MCRs generally predominate nowadays, the use of 1,3-dicarbonyls as substrates, proposed as early as 1882 by Hantzsch, proved to be highly efficient, but have been relatively unexplored until recently. In the last few years, such transformations received a growing attention as new useful methodologies valuable for the selective direct access to highly functionalized small organic molecules of primary synthetic and biological value. This review focuses on the more significant recent developments on the use of β-diketo building blocks for MCRs published in the last 5 years.

In the context of sustainable chemistry, because of economic and ecological increasing pressure, domino multicomponent reactions (MCRs) constitute a central academic and industrial investigation domain in diversity-oriented synthesis of functionalized heterocycles. Although isocyanide-based MCRs generally predominate nowadays, the use of 1,3-dicarbonyls as substrates, proposed as early as 1882 by Hantzsch, proved to be highly efficient, but have been relatively unexplored until recently. In the last few years, such transformations received a growing attention as new useful methodologies valuable for the selective direct access to highly functionalized small organic molecules of primary synthetic and biological value. This review focuses on the more significant recent developments on the use of β-diketo building blocks for MCRs published in the last 5 years.