Asymmetric Synthesis of Functionalized α-Amino Acid Derivatives via the γ-Pyrone Carbaldimine-Based Organocatalytic Mannich Reaction.

A powerful synthetic strategy for the asymmetric synthesis of enantiomerically enriched γ-functionalized α-amino acid derivatives based on the highly stereoselective proline-catalyzed Mannich-type reaction of pre-prepared or -generated γ-pyrone-derived aldimines with carbonyl compounds and subsequent transformations of multifunctional reaction products has been developed. A significant positive nonlinear effect was detected for the key organocatalytic reaction. The developed strategy was applied for facile gram-scale preparation of ()-γ-oxonorvaline, used for site-specific modification of proteins, and both enantiomers of amycolatolide A recently isolated from the lichen-derived actinomycete sp.

Concise enantioselective synthesis of non-proteinogenic α-aminoacids an organocatalytic Mannich-type reaction.

A bifunctional tertiary amine-squaramide-catalyzed enantioselective Mannich-type addition of available allomaltol to -protected aldimines was developed. The resulted adducts were readily transformed into non-proteinogenic α-amino acids and their derivatives were not easily accessible by other methods oxidative fragmentation, esterification, amidation and deprotection reactions. The absolute ()-configuration of the thus obtained α-amino acids was established by comparison of the -Ts-PheGly optical rotation sign with the reported data.

Nitration of aromatics with dinitrogen pentoxide in a liquefied 1,1,1,2-tetrafluoroethane medium.

Regardless of the sustainable development path, today, there are highly demanded chemical productions still operating that bear environmental and technological risks inherited from the previous century. The fabrication of nitro compounds, and nitroarenes in particular, is traditionally associated with acidic wastes formed in nitration reactions exploiting mixed acids. However, nitroarenes are indispensable for industrial and military applications.

2-Nitroallyl carbonate-based green bifunctional reagents for catalytic asymmetric annulation reactions.

2-Nitroallylic carbonates, a new class of "green" 1,3-bielectrophilic reagents for organic synthesis and catalysis, have been prepared. The bifunctional tertiary amine-catalyzed asymmetric [3 + 3] annulations of cyclic enols with these reagents occur much faster than corresponding reactions with 2-nitroallylic esters and produce no acidic by-products poisoning the catalyst. Furthermore, 2-nitroallylic carbonates enable highly enantioselective one-pot synthesis of a variety of fused dihydropyrane derivatives from available precursors bearing pharmacophoric fragments.

Supercritical Antisolvent Processing of Nitrocellulose: Downscaling to Nanosize, Reducing Friction Sensitivity and Introducing Burning Rate Catalyst.

A supercritical antisolvent process has been applied to obtain the nitrocellulose nanoparticles with an average size of 190 nm from the nitrocellulose fibers of 20 μm in diameter. Compared to the micron-sized powder, nano-nitrocellulose is characterized with a slightly lower decomposition onset, however, the friction sensitivity has been improved substantially along with the burning rate increasing from 3.8 to 4.

Conjugate Addition of Carbon Acids to β,γ-Unsaturated α-Keto Esters: Product Tautomerism and Applications for Asymmetric Synthesis of Benzo[]phenazin-5-ol Derivatives.

A correlation between the equilibrium ratio of tautomeric products generated by the asymmetric Michael reactions of cyclic carbon acids with β,γ-unsaturated α-keto esters and the chemical shift of the α-proton in starting nucleophilic substrates was revealed which makes equilibration predictable. New tetrahydropyran-fused benzo[]phenazins were enantioselectively (up to 99% ee) synthesized from β,γ-unsaturated α-keto esters and benzo[]phenazin-5-ol, a powerful anti-cancer agent sAJM589. Facile recyclability of catalyst in the catalytic reactions was demonstrated.

Recent advances in the asymmetric synthesis of pharmacology-relevant nitrogen heterocycles via stereoselective aza-Michael reactions.

The prevalence of nitrogen containing heterocycles in natural products and pharmaceuticals is a doubtless fact. In this review, recent applications of a stereoselective aza-Michael reaction as an efficient tool for the asymmetric synthesis of naturally occurring nitrogen-containing heterocyclic scaffolds and their usefulness to pharmacology are reviewed and summarized. The available data are for the first time classified according to types of heterocyclic products and subdivided in accordance with synthetic methodologies used as key stereocontrolling steps (diastereoselective or enantioselective reactions, single bond-forming or cascade reactions, etc.

C-Symmetric Chiral Squaramide, Recyclable Organocatalyst for Asymmetric Michael Reactions.

A very simple and highly efficient C-symmetric tertiary amine-squaramide organocatalyst for asymmetric Michael reactions has been elaborated. In the presence of only 1 mol % of this catalyst, kojic acid derivatives and β-dicarbonyl compounds reacted with nitroolefins, affording the corresponding adducts in a nearly quantitative yield with an enantioselectivity up to 99% ee. The kojic acid-derived adducts could be efficiently produced under "green" conditions (in 96% EtOH or pure water).

Asymmetric Michael addition between kojic acid derivatives and unsaturated ketoesters promoted by C-symmetric organocatalysts.

An efficient sterically hindered C2-symmetric bifunctional tertiary amine-squaramide organocatalyst for the asymmetric Michael addition/hemiketalization domino reaction of kojic acid derivatives with β,γ-unsaturated α-ketoesters has been designed. Pharmacology-relevant functionalized 2,3,4,8-tetrahydropyrano[3,2-b]pyran derivatives were produced over the catalyst in as low as 1 mol% with up to 99% yield and 99% ee. The procedure is at least 30-fold scalable and the catalyst is readily reusable in the catalytic reaction via acid-base extraction.

Asymmetric synthesis of warfarin and its analogs catalyzed by C-symmetric squaramide-based primary diamines.

Novel C2-symmetric N,N'-bis(2-amino-1,2-diphenylethyl)squaramides with 1,2-di(pyridin-2-yl)ethane and 1,2-diphenylethane spacer groups were designed and applied as organocatalysts in asymmetric additions of 4-hydroxycoumarin and 4-hydroxy-6-methyl-2H-pyran-2-one to α,β-unsaturated ketones. Both enantiomers of the anticoagulant warfarin and its analogs were prepared in up to 96% yield and with 96% ee. Recyclability of the developed catalysts and synthetic utility of the prepared Michael adducts for asymmetric synthesis of potential chiral medications via acylation reactions were demonstrated.

High diastereoselective amine-catalyzed Knoevenagel-Michael-cyclization-ring-opening cascade between aldehydes, 3-arylisoxazol-5(4H)-ones and 3-aminocyclohex-2-en-1-ones.

A highly diastereoselective three-component cascade reaction among aromatic aldehydes, 3-arylisoxazol-5(4H)-ones and 3-aminocyclohex-2-en-1-ones takes place under the catalysis of triethylamine, providing (3SR,4SR)-4-aryl-3-[(E)-(hydroxyimino)(aryl)methyl]-4,6,7,8-tetrahydroquinoline-2,5(1H,3H)-diones in 45-85% yields. The transformation presumably proceeds through a sequential cascade of Knoevenagel/Michael-addition/cyclization/ring-opening reactions. This process was carried out in green media (EtOH/water, 1:1-1:3) at reflux.

Nazarov reaction: current trends and recent advances in the synthesis of natural compounds and their analogs.

The Nazarov reaction (cyclization) is one of the most useful synthetic tools for the stereoselective preparation of various cyclopentenone scaffolds. This review summarizes recent applications of this reaction to the synthesis of natural compounds and their usefulness to pharmacology analogs published over 2005-2016. Modern protocols for the facile generation of key cationic intermediates and efficient catalytic, in particular asymmetric, versions of Nazarov cyclization are considered.

Stereospecific diaza-Cope rearrangement as an efficient tool for the synthesis of DPEDA pyridine analogs and related C-symmetric organocatalysts.

A simple and efficient synthesis of enantiomerically pure (1S,2S)-1,2-di(pyridin-2-yl)- and (1R,2R)-1,2-di(pyridin-4-yl)-ethane-1,2-diamines from commercial picolinaldehyde or isonicotinaldehyde and 2,2'-((1S,2S)-1,2-diaminoethane-1,2-diyl)diphenol (HPEN) via a stereospecific diaza-Cope rearrangement has been developed. Diamine (R,R)-2b was readily converted to novel diastereomeric ionic group-supported bis-prolinamides (R,S)-1b and (R,R)-1b which appeared to be efficient organocatalysts of asymmetric cross-aldol reactions in aldehyde/aldehyde, ketone/ketone or ketone/aldehyde reagent systems under neat conditions to afford corresponding aldols in high yields and with up to 99% ee. Furthermore, catalyst (R,S)-1b could be reused over 15 times in the same or similar catalytic reactions exhibiting close to original activity and a high level of stereoinduction.

Prospective Symbiosis of Green Chemistry and Energetic Materials.

A global increase in environmental pollution demands the development of new "cleaner" chemical processes. Among urgent improvements, the replacement of traditional hydrocarbon-derived toxic organic solvents with neoteric solvents less harmful for the environment is one of the most vital issues. As a result of the favorable combination of their unique properties, ionic liquids (ILs), dense gases, and supercritical fluids (SCFs) have gained considerable attention as suitable green chemistry media for the preparation and modification of important chemical compounds and materials.

C-Symmetric pyrrolidine-derived squaramides as recyclable organocatalysts for asymmetric Michael reactions.

Novel C-symmetric N,N'-bis-[(pyrrolidin-2-yl)methyl-squaramide] TFA salts bearing (R,R)- or (S,S)-1,2-di(pyridin-2-yl)ethane spacer groups were synthesized and applied, in combination with TEA, as efficient organocatalysts for asymmetric reactions between cyclohexanone derivatives and β-nitrostyrenes to afford the corresponding Michael adducts in high yields with good to excellent enantioselectivity. The catalytic procedure is readily scalable and recyclable over four times without a negative impact on the selectivity of the reaction. Some of the prepared compounds are valuable precursors to useful bioactive molecules.

(1,2-Diaminoethane-1,2-diyl)bis(N-methylpyridinium) Salts as a Prospective Platform for Designing Recyclable Prolinamide-Based Organocatalysts.

A new efficient and highly recyclable organocatalyst has been developed for asymmetric cross-aldol reactions under neat conditions in ketone-ketone, ketone-aldehyde, and aldehyde-aldehyde systems. The catalyst features two prolinamide fragments and a C2-symmetrical (1,2-diaminoethane-1,2-diyl)bis(N-methylpyridinium) group. The catalyst retained high activity and excellent stereoselection over the operating period of more than 830 h (25 cycles).

Chiral ionic liquid/ESI-MS methodology as an efficient tool for the study of transformations of supported organocatalysts: deactivation pathways of Jørgensen-Hayashi-type catalysts in asymmetric Michael reactions.

The deactivation pathways of Jørgensen-Hayashi-type organocatalysts modified with an ionic liquid fragment in asymmetric Michael reactions of α,β-enals with C- (nitromethane, dimethylmalonate) or N-nucleophiles (N-carbobenzyloxyhydroxylamine) that involved an iminium-ion formation step were studied for the first time by the electrospray ionization mass spectrometry (ESI-MS). "Parasitic" side reactions and undesirable cation intermediates that poisoned the catalysts were identified in accordance with their m/z values as well as their relation to the reported mechanisms of Michael reactions in the presence of O-TMS-α,α-diarylprolinol (TMS=trimethylsilyl) derivatives. The proposed approach may be useful for the study of transformations of other types of organocatalysts modified with ionic groups in various organocatalytic reactions and for the development of novel robust catalysts and processes that would be suitable for large-scale industrial applications.

Synthetic utilization of polynitroaromatic compounds. 1. S-derivatization of 1-substituted 2,4,6-trinitrobenzenes with thiols.

Reactions of 1-R-2,4,6-trinitrobenenes (R = alkyl, protected aldehyde, aminocarbonyl, cyano groups, or isoxazole ring) with thiol salts were investigated. In most cases, these reactions gave a mixture of minor para and major ortho substitution products. Reactions of N,N-disubstituted 2,4,6-trinitrobenzamides with S-,O-, and N-nucleophiles afforded products of substitution of the p-nitro group exclusively.

Synthetic utilization of polynitroaromatic compounds. 2. Synthesis Of 4,6-dinitro-1,2-benzisothiazol-3-ones and 4,6-dinitro-1, 2-benzisothiazoles from 2-benzylthio-4,6-dinitrobenzamides.

Cyclization of 2-benzylthio-4,6-dinitrobenzamides to 4,6-dinitro-1, 2-benzisothiazol-3-ones was achieved using SO(2)Cl(2) in CH(2)Cl(2) at room temperature. Alkylation of these heterocycles proceeded in a nonregioselective manner to yield a mixture of corresponding O- and N-alkylated products. Oxidation of 4,6-dinitro-1,2-benzisothiazoles (50% H(2)O(2) in AcOH) afforded the corresponding S-oxides and S, S-dioxides, depending on oxidation conditions.