Copper-catalyzed aryldifluoromethylenation of N-arylacrylamides to synthesis of the diheterocyclic compounds linked by gem-difluoromethylene moiety

An efficient method of copper-catalyzed aryldifluoromethylenation of N-arylacrylamides is described to step-economic synthesis of the various biologically important biheterocyclic compounds linked by gem-difluoromethylene moiety through addition of benzo-1,3-azolic (oxa- or thia-)difluoromethyl radicals generated in situ to terminal of C–C double bond of N-arylacrylamides then cyclization cascade. This protocol has demonstrated to have broad substrate scope and excellent functional-group tolerance under mild reaction conditions.     

A cascade process toward the synthesis of fused polycyclic dihydropyridines

The synthesis of fused polycyclic dihydropyridines was achieved using a cascade process comprising a Suzuki coupling, a nucleophilic cyclization and a hydrogen migration. Several functional groups are tolerated in this reaction and the methodology could be applied with success to quinoline and isoquinoline derivatives.     

Copper-catalyzed multicomponent cascade process for the synthesis of hexahydro-1H-isoindolones

Copper-catalyzed coupling of imines, dienylstannanes, and acryloyl chlorides followed by a Diels-Alder reaction afforded hexahydro-1H-isoindolones. Diversification of the core via Pd-catalyzed cross-coupling defines a new modular approach to isoindolone combinatorial libraries.     

A process in need is a process indeed: scalable enantioselective synthesis of chiral compounds for the pharmaceutical industry

This report deals with enantioselective synthesis of viracept 1 (nelfinavir mesylate, AG 1343), a potent HIV protease inhibitor, and 3-hydroxytetradecanoic acid 3, a component of lipid A comprising lipopolysaccharide embedded in the cell surface of Gram-negative bacteria, from both strategic and practical perspectives. As regards the synthesis of 1, the synthetic approaches to its central intermediate 2 possessing the common structural motif of 1,4-differentially substituted-2-amino-3-hydroxylbutane are mainly discussed with emphasis on the molecular symmetry that has helped streamline the synthetic strategy. In the discussion of the synthetic strategies to access a single enantiomer of 3, the chiral methodologies that have been applied so far are assessed for industrial viability; the synthetic alternatives explored include resolution via diastereomeric salt formation, lipase-catalyzed kinetic resolution, asymmetric synthesis, and chiral pool approaches.     

A denitrogenative palladium-catalyzed cascade for regioselective synthesis of fluorenes

We herein report a denitrogenative palladium-catalyzed cascade for the modular and regioselective synthesis of polysubstituted fluorenes. Hydrazone facilitates the Pd(ii) to Pd(iv) oxidative addition in a Catellani pathway and is also the methylene synthon in the proposed reaction. Aryl iodides and 2-bromoarylaldehyde hydrazones undergo a norbornene-controlled tandem reaction sequence to give a broad scope of fluorenes in the presence of a palladium catalyst. The method described is scalable and adaptable to a three-component reaction with in situ generation of the hydrazone group. Preliminary mechanistic investigations have been conducted.

Hydrazone assists Pd(ii)/(iv) oxidative addition and is the methylene synthon in a palladium-catalyzed, norbornene-mediated regioselective synthesis of fluorenes.     

Catalytic metallonitrene/alkyne metathesis: a powerful cascade process for the synthesis of nitrogen-containing molecules

A conceptually novel metallonitrene/alkyne metathesis cascade reaction has been developed for the construction of nitrogen-containing compounds from simple alkyne starting materials. Rhodium(II) tetracarboxylate salts are efficient catalysts for this reaction, in which an electrophilic rhodium nitrene is trapped by an alkyne, resulting in the formation of a new C-N bond and the generation of a reactive metallocarbene for cascade reaction. The reaction is tolerant of both alkyl and aryl substituents on the alkyne, and proceeds at room temperature in a variety of common solvents. The modular nature of the reaction allows for the rapid construction of congested bicyclic systems from remarkably simple alkyne starting materials.     

A powerful cascade approach for expeditious synthesis of trifluoromethylated furans

A powerful approach to synthesize trifluoromethylated furans has been developed. The method is operationally simple, broad in substrate scope, and amenable to scale-up using trifluoroacetic anhydride. Meanwhile, the strategy not only provided a versatile approach to synthesize trifluoromethylated furans but also provides a new method for exploring the new reactivity of trifluoroacetic anhydride.     

A new pd-catalyzed cascade reaction for the synthesis of strained aromatic polycycles

Two new palladium catalyzed cascade reactions involving a 4-exo-dig cyclocarbopalladation are described. These processes are shown to convert bromoenediynes and bromodienynes into strained aromatic compounds in a single step.     

An efficient synthesis of isocoumarins via a CuI catalyzed cascade reaction process

3-Alkyl isocoumarins are provided by CuI/amino acid-catalyzed Sonogashira coupling reaction of o-bromo benzoic acids and terminal alkynes and the subsequent additive cyclization. This cascade process allows synthesis of diverse isocoumarins by varying both coupling partners bearing a wide range of functional groups.     

A hierarchically zeolite Y for the N-heterocyclic compounds synthesis

High activity and selectivity of the hierarchical H-Ymmm zeolite in the synthesis of practically important pyridines (by interaction of C₂–C₄ alcohols with formaldehyde and ammonia, cyclocondensation of acetaldehyde and propanal with ammonia), dialkyl quinolines (by reaction of aniline with aldehydes) and alkyl dihydroquinolines (by reaction of aniline with ketones- acetone, acetophenone) were revealed in the research.The advantages of the micro-meso-macroporous H-Ymmm zeolite over the microporous H-Y zeolite in the synthesis of pyridines and quinolines were demonstrated. In the products formed by the reaction of ethanol with formaldehyde and ammonia, picolines (up to 63%) and lutidine are predominant in H-Ymmm, Pb-H-Ymmm and Fe-H-Ymmm zeolites. The interaction of n-propanol (n-butanol) with formaldehyde and ammonia in the presence of H-Ymmm zeolite with high selectivity produced 3,5-lutidine (up to 90%) or 3,5-diethylpyridine (85%). H-Ymmm zeolite makes it possible to prepare 2-methyl-5-ethylpyridine with 87% selectivity (reaction of acetaldehyde with ammonia) and 2-ethyl-3,5-dimethylpyridine with 58% selectivity (reaction of propanal with ammonia).The synthesis of dialkylquinolines and dialkyltetrahydroquinolines with a total selectivity of 65–73% by the interaction of aniline with C₃–C₅ aldehydes has been carried out. The dihydroquinoline derivatives with the selectivity of up to 70% have been synthesized by the reaction of aniline with ketones (acetone, acetophenone).     

A four-step enzymatic cascade for the one-pot synthesis of non-natural carbohydrates from glycerol

A total of four enzymatic steps were combined, in a one-pot reaction, to synthesize carbohydrates starting from glycerol. First, phosphorylation of glycerol by reaction with pyrophosphate in the presence of phytase at pH 4.0 in 95% glycerol afforded racemic glycerol-3-phosphate in 100% yield. The L-enantiomer of the latter underwent selective aerobic oxidation to dihydroxyacetone phosphate (DHAP) at pH 7.5 in the presence of glycerolphosphate oxidase (GPO) and catalase. Subsequently, fructose-1,6-bisphosphate aldolase catalyzed the aldol reaction of DHAP with butanal. Finally, dephosphorylation of the aldol adduct was mediated by phytase at pH 4 affording 5-deoxy-5-ethyl-D-xylulose in 57% yield from L-glycerol-3-phosphate. The phytase on/off-switch by pH was the key to controlling phosphorylation and dephosphorylation.     

A pericyclic cascade to the stereocontrolled synthesis of 9-cis-retinoids

A domino reaction that is pericyclic in nature is thought to be triggered upon treatment of alkenynol 10 with arylsulfenyl chlorides. The process comprises an ordered sequence of sigmatropic rearrangements: a reversible [2,3]-allyl sulfenate to allyl sulfoxide shift, followed by a [2,3]-propargyl sulfenate to allenyl sulfoxide rearrangement, and last a stereodifferentiating [1,5]-sigmatropic hydrogen migration leading to polyene 13. The occurrence of the C7 to C11 hydrogen migration has been demonstrated by labeling experiments. The double diastereoselection of the [1,5]-sigmatropic hydrogen shift to afford a single isomer of the final polyene 13 is thought to arise from a combination of the electronic effect of the sulfoxide at one terminus, and the steric effect imparted by the bulky trimethylcyclohexenyl substituent at the other terminus. The overall process thus constitutes a stereoselective synthesis of an E,Z,Z-triene fragment from an alkenynol and, in particular, a retinoid with the 7E,9Z,11Z,13E configuration on the conjugated polyenic side chain. Application of this method to the synthesis of retinoids, including labeled analogues, is straightforward.     

A new method for the synthesis of organopolyoxometalate hybrid compounds

The reaction of a quaternary ammonium salt of the tin chloride-substituted polyoxometalate, [PSn(Cl)W11O39]4-, with a variety of n-nucleophiles including primary, secondary, and tertiary amines and a tertiary phosphine, yielded tin-centered Lewis acid-base adducts, [PSn(Cl)W11O39]4--n-nucleophile; with more nucleophilic secondary amines such as diisopropylamine, apparently some [PSnN[CH(CH3)2]2W11O39]4- was formed as a minor product. The compounds were identified by 1H, 119Sn, 15N, 31P, and 183W NMR, ESI-MS, and elemental analyses. The key connectivity of the Sn-Cl center with the amine was clarified by the observation of 3J Sn-H couplings (Sn from the polyoxometalate cluster and H from the amine moiety) in a 2D 119Sn-1H heteronuclear multiple-bond correlation NMR experiment. This new, rather simple synthetic method was also utilized for preparing amino acid-polyoxometalate hybrid compounds.     

A two-stage iterative process for the synthesis of poly-oxazoles

[reaction: see text]. Methodology has been developed to prepare bis-oxazoles via a two-stage iterative process. The sequence begins with C(2)-chlorination of a lithiated oxazole using hexachloroethane. Generation of the C(2)-C(4)(') bond by S(N)Ar substitution with TosMIC anion, followed by conversion to the heterocycle in a one-pot reaction with glyoxylic acid monohydrate, affords the desired bis-oxazole in good yield and purity. The two-stage process allows for efficient synthesis of a tris-oxazole and the first iterative preparation of a tetra-oxazole.     

An efficient one-pot asymmetric synthesis of biaryl compounds via Diels-Alder/retro-Diels-Alder cascade reactions

[reaction: see text] A single-step chirality transfer method for the synthesis of axially chiral biaryl compounds by construction of the second aromatic ring via a Diels-Alder/retro-Diels-Alder cascade reaction is reported. This methodology should find broad application in the synthesis of natural products and asymmetric catalysts.     

Rhodium-catalyzed cascade reactions: A methylenation-hydroboration homologative process

A very efficient rhodium-catalyzed cascade process allowing the transformation of aldehydes and ketones into their corresponding one or two-carbon homologated alcohol products through a methylenation-hydroboration sequence is reported. Wilkinson’s complex is used to catalyze both reactions in a one-pot procedure that does not require the isolation of the alkene intermediate.     

含能化合物合成中典型反应过程的热效应

分别以尿素硝化制备二硝基脲、DATF氧化制备DNTF、DINA叠氮化制备叠氮硝胺工艺为研究对象,利用反应量热仪实验测定了三种典型单元反应过程的热量释放数据。结果表明,尿素硝化反应放热量为1.63kJ·g-1(以尿素计),最大放热速率为174.7 W;DATF氧化反应放热量为2.26 kJ·g-1(以DATF计),最大放热速率为64.7 W;DINA叠氮化反应放热量为0.88 kJ·g-1(以NaN3计),最大放热速率为90.1 W,同时获得各反应过程中的物料传热系数与比热容随时间变化曲线,为工艺设计与过程安全性研究提供理论依据。