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Density functional theory calculations have been performed to address the detailed mechanism of phosphine-catalyzed hydroboration of propiolonitriles. The mechanism with the cyano participation was hindered by an inaccessible free-energy barrier of 42.3 kcal/mol, while the conventional one without the cyano participation was identified to be plausible. The involved elementary steps include nucleophilic addition of PBu 3 , 1,2-hydride transfer, 1,2-boron migration and removal of PBu 3 in succession, with the rate-determining free-energy barrier of 21.4 kcal/mol. The anti -addition stereoselectivity originated from the steric effect in the 1,2-boron migration step, and the complete regioselectivity was governed by the positional preference of PBu 3 attack. Lastly, the strongly electron-withdrawing effect of cyano was found to facilitate the desired hydroboration at room temperature by stabilizing some zwitterionic intermediates and transition states. This study provided a preciser understanding on the mechanism of phosphine-catalyzed hydroboration and unveiled factors governing the reactivity and selectivity. The mechanism of phosphine-catalyzed hydroboration of propiolonitriles was explored by density functional theory calculation. The regio- and stereoselectivity were addressed in detail. The role of the cyano substituent was unveiled. [Display omitted] [ABSTRACT FROM AUTHOR]

A mild base-promoted three-component deconstructive functionalization reaction of cyclic 1,3-diketones with aryl diazonium tetrafluoroborates in the presence of alcohols is reported, enabling direct ring-opening of unstrained cyclic ring systems to produce three types of skeletally diverse 1,n-ketoesters, namely, linear 1,5- and 1,4-ketoesters and ortho -ketobenzoates, with moderate to good yields. The methodology has the potential to be widely used throughout organic synthesis due to the use of easily accessible substrates, such as cyclic 1,3-diketones and aryl diazonium tetrafluoroborates, with different substitution patterns and mild reaction conditions. To create your abstract, type over the instructions in the template box below. Fonts or abstract dimensions should not be changed. [Display omitted] [ABSTRACT FROM AUTHOR]

The 1,3-dipolar cycloaddition of 3-nitro-2(1 H)-quinolones with azomethine ylides derived from sarcosine or thiazolidine-4-carboxylic acid and various 1 H -indole-2,3-diones (isatins) have been investigated. The structure and stereochemistry of the formed cycloadducts were studied in detail by X-ray diffraction and NMR spectroscopy methods. [Display omitted] [ABSTRACT FROM AUTHOR]

A novel four-component (five-molecular) diastereoselective synthesis of pyridinium salts of 2-piperidinones is reported. The Knoevenagel–Michael–Mannich cascade of reactions of aromatic aldehydes (2 eq.), nitriles, pyridinium ylides and ammonium acetate in ethanol provides convenient access to 1-((3 R*, 4 S*, 6 R*)-5,5-dicyano-2-oxo-4,6-diarylpiperidin-3-yl)pyridin-1-ium halogenides with three stereocenters (55–85 % yields) or 1- (3 R*, 4 S*, 5 S*, 6 R*) -(5-cyano-5-(alkoxycarbonyl)-2-oxo-4,6-diarylpiperidin-3-yl)pyridin-1-ium halogenides with four stereocenters (56–84 % yields). [Display omitted] [ABSTRACT FROM AUTHOR]

We report herein an original protocol to the indole nucleus, which could contribute to significantly expand the synthetic access to a heterocyclic moiety of undeniable paramount importance. The protocol consists in the construction of the benzene ring onto a pyrrole (benzannulation) starting from 2,3-dinitro-1,3-butadienes. This appealing, metal-free process characterized by high atom economy and mild reaction conditions allows to synthesize indoles possessing nitro group(s) on the benzene ring: a result which cannot be likewise easily obtained by exploiting most common pathways such as functionalization of a preformed indole or heteroannulation of a suitable benzene derivative. From a mechanistic point of view, a stepwise, ionic process is suggested by the identification of a pivot dihydroindole intermediate whose interception facilitates some selectivity in the preparation of different nitroindoles. Image 1 [ABSTRACT FROM AUTHOR]

Upon treatment with the metal enolates of methylene active compounds (dimethyl malonate and dibenzoylmethane) (C -nucleophiles) and benzyl carbamate (N -nucleophile), d -allal- and d -galactal-derived vinyl epoxides are stereoselectively transformed, in a single step, into diastereoisomeric, highly functionalized, enantiopure cis - and trans -2,5-disubstituted-2,5-dihydrofurans. Image 1 [ABSTRACT FROM AUTHOR]

A density functional study of the [2 + 2] cycloaddition between methyleneindolinones and enals catalyzed by prolinol derivatives is presented here. The calculations show that dienamines could be generated under acid-free conditions, and the hydroxyl of the catalysts plays a key role in the formation of dienamines. The following cycloaddition process between methyleneindolinones and the new formed dienamines includes two-step intramolecular electron transfers. The stereoselectivity is mainly attributed to the charge distributions on the reaction centers and the H-bonding interaction between the catalysts and methyleneindolinones. The excellent 3,4-regioselectivity is largely ascribed to the fact that the pre-product of 1,2-reactivity is tough to hydrolyze, but could return to the precursor. Besides, the large steric hindrance of catalysts is not conducive to the 3,4-reactivity, while the H-bonding between the catalysts and methyleneindolinones has less effect on the regioselectivity. The reactivity and selectivity of the [2 + 2] cycloaddition between methyleneindolinones and enals catalyzed by prolinol derivatives were investigated using DFT M05-2X methods. Image 1 • The hydroxyl of catalysts is critical for the formation of dienamines without acid. • The [2 + 2] cycloaddition process contains two-step intramolecular electron transfers. • The stereocenters mainly stems from the charge distributions on the reaction center. • The H-bonding interaction plays a vital role in the stereoselectivity. • The 3,4-regioselectivity depends on the hard hydrolysis of the 1,2-pre-product. [ABSTRACT FROM AUTHOR]

For nearly two decades, synthetic chemists have been fascinated by the structural complexity and synthetic challenges afforded by the guanacastepene and heptemerone diterpenoids. Numerous synthetic approaches to these compounds have been reported, but to date the application of enantioselective catalysis to this problem has not been realized. Herein we report an enantioselective synthesis of an advanced intermediate corresponding to the tricyclic core common to the guanacastepenes and heptemerones. Highlights of this work include sequential Pd-catalyzed decarboxylative allylic alkylation reactions to generate the two all carbon quaternary stereocenters, the use of ring-closing metathesis to close the A ring in the presence of a distal allyl sidechain, and a regio- and diastereoselective oxidation of a trienol ether to introduce oxygenation on the A ring. Image 1 [ABSTRACT FROM AUTHOR]

Ceric ammonium nitrate-mediated oxidative cyclizations of CH-acids with terpenes and terpene like substrates were investigated. Dimedone, acetylacetone, and methyl nitroacetate were condensed with pinene, norbornene, nopol, camphene, and carvone and the reaction stereoselectivity was examined. Condensation with endocyclic double bonds in pinene and nopol displayed stereoselectivity, resulting in the formation of pure enantiomers. Condensation with exocyclic double bonds in camphene and carvone produced enantiomer mixtures. The mechanism of the intramolecular annulation in a nopol derivative is discussed with the help of DFT and ab initio calculations. Image 1 [ABSTRACT FROM AUTHOR]

Abstract Dirhodium(II)-catalyzed oxonium ylide formation–[2,3]-sigmatropic rearrangement of 6-allyloxy-2-diazo-3-ketoesters possessing a C-6 substituent is described. The reaction of 6-alkyl- or 6-aryl-substituted 6-allyloxy-2-diazo-3-ketoesters with a catalytic amount of Rh 2 (S -PTTL) 4 proceeded in a chemoselective and stereoselective manner to provide 6-substituted 2-allyl-3-oxotetrahydropyran-2-carboxylates in good yields and with high diastereoselectivities. To demonstrate the utility of this sequential reaction, we conducted the total synthesis of (+)-tanikolide, in which the construction of the δ-lactone skeleton was achieved by employing a 2-iodobenzamide-catalyzed oxidative cleavage of tetrahydropyran-2-methanol. Graphical abstract Image 1 Highlights • Six-membered oxonium ylide formation-[2,3]-sigmatropic rearrangement is described. • The reaction using Rh 2 (S -PTTL) 4 proceeded in a chemo- and stereoselective manner. • The Rh(II)-catalyzed reaction could be applied to the total synthesis of tanikolide. [ABSTRACT FROM AUTHOR]

Abstract Nitroso-ene (NE) reactions have been adapted in the construction of nitrogen-containing motifs in many biologically interesting compounds. The transient and highly reactive "nitroso" species remains a challenge for designing stereocontrolled syntheses. Although chiral auxiliary-based method has been developed to achieve high diastereoselectivity, the use of the inherent chirality of the nitroso compound for stereochemical control remains underdeveloped. We chose the formation of a γ-lactam via a NE cyclization as a basis to study the applicable principles for future asymmetric syntheses. The selected examples presented herein reveal that the intramolecular hydrogen bond would provide conformational restraint to facilitate excellent facial selectivity in the NE reaction via a chair-like transition state. The sterically bulky amino group also provides excellent stereochemical control possibly through steric repulsion. The following transformations led to a key intermediate (Ohfune's lactone) in the preparation of manzacidins A and C and thus constitutes a formal synthesis. Graphical abstract Image 1 Highlights • Stereochemistry in the nitroso-ene cyclization: intramolecular hydrogen-bonding and steric hindrance effect. • Application in the stereodivergent synthesis of manzacidins A and C. • Construction of nitrogen-containing quaternary carbon center through nitroso-ene reaction. [ABSTRACT FROM AUTHOR]

Abstract Transition metal catalysis has enabled the highly stereoselective and protecting group-free synthesis of the C14 C23 fragment of the apoptosis-inducing natural products biselyngbyolide A and B. A Pd-catalyzed Stille reaction between a vinyl stannane and a crotyl carbonate formed the skipped diene with complete control of the trisubstituted bond and excellent control over the branched/linear products. A Cu-catalyzed Stahl oxidation was used to form the requisite aldehyde needed for a Ag-catalyzed asymmetric allylation. The latter provided the final fragment with excellent stereochemical control. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Abstract This review is focused on the recent advances in the functionalization of allenes via radical process. Different radical partners including carbon radicals and heteroatom radicals are discussed in the reactions of allenes. Generally, the radical formed in situ would attack the allene at the central carbon leading to allyl radical intermediate. However, the formation of alkenyl radical intermediate from allene could be observed as well in some cases with high regioselectivity and stereoselectivity. Graphical abstract Recent advances in the functionalization of allenes via radical process are summarized. Different radical partners including carbon radicals and heteroatom radicals are discussed in the reactions of allenes. Image 1 [ABSTRACT FROM AUTHOR]

Abstract A general and highly selective method for the synthesis of carbohydrate-derived ( Z )-vinyl halides and silanes is described. This reaction takes place through a β-elimination process of sugar-derived α-halomethylcarbinol acetates promoted by samarium diiodide. Starting materials have been easily prepared in two steps consisting in an initial addition of halomethyllithium compounds to the corresponding galactose-derived aldehyde, followed by acetylation. A mechanism that explains both the formation of ( Z )-vinyl derivatives and its selectivity is proposed. Finally, the synthetic usefulness of these compounds has been applied in cross-coupling reactions with ethynyl benzene towards the formation of selected enyne derivatives. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

The title compounds were synthesized from the selectively protected N -acylated d -glucosamine derivatives, containing α-halo carboxylic acid moieties, via intramolecular 3- O -alkylation. It was found that if the starting compound contains asymmetric electrophilic center, isomuramic acid derivatives were mainly formed, regardless of the configuration of the electrophilic carbon atom. An explanation for the observed stereochemical results was proposed on the basis of the analysis of steric interactions in the molecules of the starting compounds, as well as using the concept of anchimeric assistance. It was shown that N -acetylation of the obtained lactam derivatives and subsequent methanolysis under mild conditions led to the selective cleavage of δ-lactam ring resulting in the formation of the corresponding ester derivatives of N -acetylmuramic acid or its analogues in high yields. [ABSTRACT FROM AUTHOR]

The stereoselective synthesis of 5,5-spiroacetals by Rh(II)-catalysed double C–H insertion of methylene acetals bearing two diazo ester substituents is described. The diastereoselectivity of this bidirectional approach can be tuned through appropriate choice of catalyst, and chiral catalysts lead to products with up to 89% ee . The diastereoselectivity of the first cyclisation suggests that the second cyclisation proceeds via a non-concerted pathway. [ABSTRACT FROM AUTHOR]

Phenoxathiin-based thiacalix[4]arene, obtained by the acid-catalysed rearrangement of the corresponding spirodienone derivative, was immobilized using the alkylation with chloroacetonitrile to yield three (out of four theoretically possible) stereoisomers. As the conformational outcome of the reaction could not be unambiguously assigned using standard NMR techniques, the method of Residual Dipolar Coupling constants (RDCs) was applied. The measuring of an anisotropic through-space dipole-dipole interactions in the lyotropic liquid crystalline alignment medium (PELG, poly-γ-ethyl- l -glutamate, and PBLG, poly-γ-benzyl- l -glutamate) enabled the assignment of the individual conformers. The usefulness of this approach was finally confirmed by the X-ray crystallography data. [ABSTRACT FROM AUTHOR]

A new sulfenylation reaction has been established, stereoselectively affording 37 examples of α -arylthio- α,β -unsaturated ketones with generally good yields via a metal-free three-component reaction of α -thiocyanate ketones with diaryliodonium salts and 1,2-dicarbonyls. The reaction enabled multiple bond-forming events including C(sp 2 )–S formation to provide a high-efficient and practical method toward α -arylthio- α,β -unsaturated ketones. The reasonable mechanism for forming α -arylthio- α,β -unsaturated ketones was proposed. [ABSTRACT FROM AUTHOR]

A concise and operationally simple photocatalysis strategy for the annulative cyanoalkyletherification of 1,6-enynes with cyclic oxime esters and alcohols is reported, producing a set of functionalized 1-indanones bearing an all-carbon quaternary center with generally good yields. In this process, single electron reduction of cyclic oxime esters drives deconstructive carbon−carbon σ-bond cleavage to yield a key cyanopropyl radical poised for addition−cyclization. This reaction is redox-neutral and demonstrates good functional group compatibility and a wide substrate scope, in which diversified alcohols can be engaged in the annulation reaction to prepare exocyclic vinyl ethers. [Display omitted] [ABSTRACT FROM AUTHOR]

The reaction of 3-nitro-2-trifluoro(trichloro)methyl- and 3-nitro-2-phenyl-2 H -chromenes with 1-morpholinocyclopentene under the conditions of kinetic or thermodynamic control led to the formation of products due to enamine addition at the C-4 atom of chromene as individual cis,trans - or trans,trans -isomers, differing by the position of double bond in the enamine moiety. Hydrolysis of these compounds in dilute HCl did not cause changes of pyran ring configuration and provided the respective 4-(cyclopentanon-2-yl)chromanes with anti -configuration of hydrogen atoms at the С-4 and С-2 ′ atoms. Stereochemistry of the obtained compounds was confirmed by X-ray structural analysis. [ABSTRACT FROM AUTHOR]

A stereoselective hydrogenation of 1,3-diynes with an air-stable copper(I)/N-heterocyclic carbene complex, [IPrCuOH], has been developed. The corresponding products, 1,3-dienes, are obtained in a stereoselective manner depending on their substitution pattern: Diaryl-diynes yield E,E -1,3-dienes, whereas dialkyl-diynes are converted to the corresponding Z,Z -1,3-dienes. Hydrogenation and deuteration experiments with enynes indicate that these are competent reaction intermediates in the hydrogenation of diynes. [ABSTRACT FROM AUTHOR]

A Cu-catalyzed radical reaction of Cl 2 C(CN) 2 was utilized for stereoselective conversion of unsaturated molecules into functionalized carbocycles. Chloromalononitrile radicals, generated by treating Cl 2 C(CN) 2 with catalytic amounts of CuCl and dppf in refluxing dioxane, intermolecularly reacted with the unsaturated bonds of acyclic or 10-membered compounds. The resultant carboradicals then intramolecularly added to another unsaturated bond to produce 1,2-disubstituted cyclopentane or trans -decalin derivatives. The chemo- and stereoselectivities of these radical cascade reactions are discussed in detail. [ABSTRACT FROM AUTHOR]

Tests of antiproliferative activity of Mannich adducts of aromatic nucleophiles and a chiral bicyclic imine revealed a di- tert -butylphenol derivative as a promising compound for further exploration. To study the influence of substitution pattern and a configuration of stereogenic centers on the inhibition of cancer cell growth, a series of Mannich bases were obtained with a good to high diastereoselectivity from the reaction of the imine and three isomeric di- tert- butylphenols. Six new enantiopure adducts were isolated and fully characterized. Selected derivatives were shown to exhibit an interesting antiproliferative activity comparable to cisplatin. [ABSTRACT FROM AUTHOR]

Singlet-oxygenation of 3-hydroxyphenyl-substituted dihydrofurans fused with a cyclohexane 1a − c exclusively gave the corresponding syn/anti -stereoisomeric mixtures of dioxetanes 2a − c . The syn/anti -π-facial selectivity in the 1,2-cycloaddition of singlet oxygen ( 1 O 2 ) was found to be remarkably sensitive to the solvent as well as the reaction temperature. In fact, the solvent effect was so conspicuous that inversion of the syn/anti -π-facial selectivity was observed in different solvents, such as chloroform and toluene. An LSER (linear solvation energy relationships) analysis suggested that the Lewis-acidity/basicity and HBD (hydrogen-bond donor)/HBA (hydrogen-bond acceptor) ability as well as dipolarity/polarizability of the solvent played an important role in this change in syn/anti -π-facial selectivity. An investigation of the temperature-dependency of the singlet-oxygenation suggested that the syn/anti -π-facial-selective 1,2-cycloaddition of 1 O 2 to 1 was a conformationally-(entropy-) controlled process. [ABSTRACT FROM AUTHOR]

A new protocol for the synthesis of d -galactal-derived N -ethoxycarbonyl vinyl aziridine 1β-CO 2 Et , starting from tri- O -acetyl- d -glucal, is described. The new protocol constitutes a simple and fast access, with a satisfactory overall yield (5 steps, 36%), to a d -galactal-derived vinyl aziridine with a clear improvement compared with the previously described procedure leading to the structurally related N -nosyl aziridine 1β-Ns which, starting from the same precursor, proceeded through 13 steps with a low, decidedly unsatisfactory, overall yield (3%). [ABSTRACT FROM AUTHOR]

Diels-Alder reactions of substituted cyclobutenones with 6-methoxy-1-vinyl-3,4-dihydronaphthalene and methoxy-substituted-1,3-butadiene have been studied with DFT. In the reactions of 6-methoxy-1-vinyl-3,4-dihydronaphthalene with cyclobutenone and α-bromocyclobutenone, the formation of the meta and ortho isomers have the same barriers, indicating that the two isomers might be formed in equal proportions, contrary to earlier reports. The regiochemistry of the reaction is mainly controlled by the ketone functionality at C1 on the dienophiles. In the reactions of methoxy-substituted-1,3-butadiene with cyclobutenone and α, β-substituted cyclobutenones the ortho/endo and para/endo stereo-isomeric pathways are the most favorable pathways, changing to exo selectivity when OH, Br, CH 3 are placed on the β-carbon of the cyclobutenone, but still with ortho and para regioselectivity. The stereoselectivity is independent of the bulkiness of substituents. The stability of substituted cycloadducts are lower compared to unsubstituted adducts and this explains why the α-cyanoketones and α-bromoketone products readily undergo trans -methylation and angular-alkylation as electrophiles. [ABSTRACT FROM AUTHOR]

A series of the derivatives of chondroitin sulfate E (CS-E) disaccharide repeating unit were prepared by postglycosylation–oxidation strategy. The strategy showed excellent performance in glycosylation both on the reactivity and stereoselectivity. Different protecting methodologies were used for the manipulation of disaccharide building blocks. Substitutes at C-4 of glucosyl donors mildly influenced the glycosylation. The current synthesis afforded a feasible approach for the preparation of CS-E repeating unit. [ABSTRACT FROM AUTHOR]

A multi-component bicyclization strategy has been established, allowing a flexible and practical approach to 29 examples of skeletally diverse fused quinazolines from low-cost and readily accessible aldehydes with cycloketones and cyanoamides. The reaction is easy to perform simply by mixing three common reactants and Cs 2 CO 3 in ethylene glycol under microwave irradiation and can be finished within 25 min with water as a sole byproduct. A sequence cascade process consisting of Knoevenagel condensation/[4+2] cyclization/intramolecular aza-Michael addition/aza-nucleophilic reaction-ring opening is involved in this new scaffold generating reaction. During this sequence, four stereogenic centers with one quaternary carbon-amino functionality have been controlled very well; and the stereochemistry has been unequivocally determined by X-ray structural analysis. [ABSTRACT FROM AUTHOR]

This present work reported a detailed DFT study to the reaction mechanism and stereoselectivities of the NHC-catalyzed [4+2] cycloaddition of ketenes with 1-azadienes. The calculated results reveal that the ‘ketene-first’ mechanism is more energetically favorable than the ‘azadiene-first’ one, and the cycloaddition step is demonstrated to be both the rate- and stereoselectivity-determining step. The Gibbs free energy barrier to afford the product in SS configuration is lower than those in other configurations, which is well consistent with the experimental results. Analyses to the distortion–interaction energies of two key species and the components of the free energy barriers of the step in which the stereocenters generate were conducted, and it was concluded that stereoseletivities of the reaction should originate from differences of enthalpy barriers via the four transition state isomers, rather than the distinctions of barriers stemming from entropy penalties. [ABSTRACT FROM AUTHOR]

Backbone-fluorinated gamma-amino acids are novel shape-controlled building blocks that have potential utility in a variety of biological contexts. However, their synthesis poses challenges in terms of chemo-, regio- and stereoselectivity, and this has proven to be the major bottleneck in the ongoing development of their various biological applications. To address this problem, several new synthetic strategies were investigated in this work. This has led to the identification of new methods that are superior in terms of yield and stereocontrol. [ABSTRACT FROM AUTHOR]

The four component reactions involving diazoamides, amines, aldehydes, exomethylenes/imines were performed in the presence of copper(I) thiophenecarboxylate as a catalyst to afford dispiroindolo-pyrrolidine/-imidazolidine derivatives in good yield with regio-, chemo- and diastereoselective manner. The structure and stereochemistry of dispiroheterocyclic ring systems were confirmed based on the representative single-crystal X-ray analysis. These reactions involve the generation of intermolecular azomethine ylide intermediates and the subsequent 1,3-dipolar cycloaddition process with olefins or imines. [ABSTRACT FROM AUTHOR]

A convergent total synthesis of promysalin, a metabolite of Pseudomonas putida RW10S1 with antibiotic activity, is described. The synthetic approach is based around a salicyldehydroproline core and a dihydroxymyristamide fragment. Crucial steps include a MacMillan asymmetric α-hydroxylation applied for the construction of the myristamide framework, and a lactam reduction by Superhydride ® to obtain the dehydroproline fragment. Because of the modular nature of the synthesis, ready access to analogues for biological evaluation is available. [ABSTRACT FROM AUTHOR]

Intramolecular cyclopropanation followed by ring opening of remotely placed furan was demonstrated using rhodium(II) catalysed cyclic diazoamides tethered on furan to produce 12- to 23-membered oxindole incorporated macrocycles. The length of the spacer is an important factor to decide the stereoselectivity of the product. [ABSTRACT FROM AUTHOR]

The regio- and stereoselective glycosylation at the 6-position in 2,3,4,6-unprotected hexopyranosides has been investigated with dibutyltin oxide as the directing agent. Perbenzylated hexopyranosyl bromides were employed as the donors and the glycosylations were promoted by tetrabutylammonium bromide. The couplings were completely selective for both glucose and galactose donors and acceptors as long as the stannylene acetal of the acceptor was soluble in dichloromethane. This gave rise to a number of 1,2-cis-linked disaccharides in reasonable yields. Mannose donors and acceptors, on the other hand, did not react in the glycosylation under these conditions. [ABSTRACT FROM AUTHOR]

Reactions of 2-R-3-nitro-2 H -chromenes (R=CF 3 , CCl 3 , Ph) with α-morpholinostyrene in acetonitrile proceed diastereoselectively to give mainly trans – cis -2,3,4-trisubstituted chromane enamines at room temperature and trans – trans -chromane enamines at 60 °C as a result of nucleophilic addition at the C-4 atom of the chromene system. Acid hydrolysis of these compounds proceeded with retention of the configuration of the pyran ring and gave 4-phenacylchromanes. The stereochemistry of the products was established by X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]