Allyl Cyanide Research Articles

Enantioselective Synthesis of Axially Chiral Allylic Nitriles via Nickel-Catalyzed Desymmetric Cyanation of Biaryl Diallylic Alcohols.

Axially chiral nitriles are common motifs in organic photoelectric materials, biological compounds, and agrochemicals. Unfortunately, the limited synthetic approaches to axially chiral nitriles have impeded their availability. Herein, we report the first nickel-catalyzed desymmetric allylic cyanation of biaryl allylic alcohols for the synthesis of axially chiral nitrile structures in high yields with excellent enantioselectivities (up to 90 % yield and >99 % ee). This process enables the synthesis of a diverse range of axially chiral allylic nitriles bearing β,γ-unsaturated alcohol moieties. Leveraging the allylic alcohol and cyano groups as versatile functionalization handles allow for further derivatization of these axially chiral frameworks. Density functional theory (DFT) calculations suggest that both steric and electronic interactions play crucial roles in determining the enantioselectivity of this transformation. Moreover, this mild and facile protocol is also applicable for gram-scale preparation of the chiral nitriles.

Enantioselective Synthesis of Axially Chiral Allylic Nitriles via Nickel‐Catalyzed Desymmetric Cyanation of Biaryl Diallylic Alcohols

AbstractAxially chiral nitriles are common motifs in organic photoelectric materials, biological compounds, and agrochemicals. Unfortunately, the limited synthetic approaches to axially chiral nitriles have impeded their availability. Herein, we report the first nickel‐catalyzed desymmetric allylic cyanation of biaryl allylic alcohols for the synthesis of axially chiral nitrile structures in high yields with excellent enantioselectivities (up to 90 % yield and >99 % ee). This process enables the synthesis of a diverse range of axially chiral allylic nitriles bearing β,γ‐unsaturated alcohol moieties. Leveraging the allylic alcohol and cyano groups as versatile functionalization handles allow for further derivatization of these axially chiral frameworks. Density functional theory (DFT) calculations suggest that both steric and electronic interactions play crucial roles in determining the enantioselectivity of this transformation. Moreover, this mild and facile protocol is also applicable for gram‐scale preparation of the chiral nitriles.

Pd-Catalyzed Hydrocyanation of Methylenecyclopropanes: A Highly Selective Ring-Opening Access to 2-Substituted Allylic Nitriles.

Transition-metal-catalyzed hydrofunctionalization of methylenecyclopropanes presents a useful but challenging transformation due to the complex selectivity and multiple reaction pathways. We describe herein an unprecedented highly efficient and selective palladium-catalyzed hydrocyanation of methylenecyclopropanes to give various 2-substituted allylic nitriles. Mechanistic studies demonstrated that the transformation may undergo Markovnikov-type hydrometalation and β-carbon elimination.

Nickel-Catalyzed Cyanation of Allylic Alcohols: High Degree of Chiral Inversion in Aqueous Reaction Media.

Nickel-catalyzed aqueous cyanation of allylic alcohols is herein described. This catalytic protocol provided environmentally friendly and operationally simple access to a variety of allylic nitriles in good yields. For chiral allylic alcohols, the reaction gave chiral allylic nitriles with a high degree of chiral inversion. The accelerated release of cyanide in H2O was crucial for the success of this reaction.

Tandem [5,5]-/[3,3]-Rearrangements of Aryl Sulfoxides with Allyl Nitriles

AbstractTandem aromatic rearrangements represent a potent strategy for modulating the regioselectivity of a rearrangement process. In this article, we disclose two novel tandem aromatic rearrangements triggered by sulfonium [5,5]-rearrangement recently developed in our laboratory. Specifically, the [5,5]-rearrangement of aryl sulfoxides with allyl nitriles, followed by [3,3]-Cope rearrangement, forges a seamless tandem [5,5]-/[3,3]-rearrangement cascade, affording ortho-functionalized aryl sulfides. The other tandem process involves [5,5]-rearrangement of aryl sulfoxides with allyl nitriles, followed by nucleophilic addition/DDQ-oxidation-induced [3,3]-Cope rearrangement, eventually yielding meta-functionalized aryl sulfides. Both consecutive rearrangements enrich the repertoire of tandem aromatic rearrangement methodologies.

Numerical analysis and early detection ofPlasmodium falciparum using a high performanceplasmonic biosensor with an external sensingapproach.

The authors propose a surface plasmon resonance (SPR) sensor based on photonic crystal fibers (PCFs) using three hexagonal ring lattices. The sensor can detect biomolecules with maximum wavelength and amplitude sensitivities of 23,000nm/RIU and 1310.93R I U -1, respectively, in the RI range of 1.32 to 1.42. It can detect infected red blood cells with Plasmodium falciparum for RIs of 1.402, 1.373, 1.395, and 1.383 in various malaria-infected red blood cell stages, including ring phase, trophozoite phase, and schizont phase. Furthermore, the sensor will be able to detect biomolecules such as viruses, proteins, DNA/RNA strands, acetone, ethanol, hexane, isopropanol, hexanol, formic acid, allyl cyanide, and others in its range. With these impressive results and identification capacity, the proposed sensor would benefit the biomaterial field and be appropriate for the early identification of malaria disease.

Oxidative triflamidation of allyl cyanide in nitrile solutions

The reaction of triflamide with allyl cyanide in benzonitrile and isobutyronitrile solutions in the presence of NBS has been studied. In both cases, the corresponding amidines - the products of the solvent incorporation are formed. In benzonitrile, depending on the reaction conditions, the isomeric N -(2-bromo-3-cyanopropyl)- N '-(triflyl)benzamidine and N -(1-bromo-3-cyanoprop-2-yl)- N '-(triflyl)benzamidine were obtained in various ratio. From the reaction in isobutyronitrile, N -(2-bromo-3-cyanopropyl)- N '-(triflyl)isobutyramidine and the product of diamination, N -[3-cyano-1-(triflamido)propyl]isobutyramide were isolated.

Construction of Cyclobutane‐Centered Tricyclic Caged Skeleton through a [5,5]‐Rearrangement Triggered Cascade

AbstractIn this report, we describe the combination of [5,5]‐rearrangement‐triggered dearomatization recently developed in our laboratory with an intramolecular formal [2+2]‐cycloaddition for constructing an intriguing polysubstituted tricyclo[4.2.1.03,8]nonane derivatives. The synthesis features the use of simple and readily available three distinct starting materials including aryl sulfoxides, allyl nitriles, and certain nucleophiles or dienes which directly enriches the diversity of target molecules. This study provides an entirely new protocol for the synthesis of cyclobutane‐centered tricyclic caged skeleton.

Oxidative Triflamidation of Allyl Cyanide in Nitrile Solutions

Oxidative Triflamidation of Allyl Cyanide in Nitrile Solutions

Catalytic Enantioselective Construction of Chiral γ-Azido Nitriles through Nitrile Group-Promoted Electrophilic Reaction of Alkenes.

An efficient approach for the construction of enantioenriched γ-azido nitriles through the chiral sulfide-catalyzed asymmetric electrophilic thioazidation of allylic nitriles is disclosed. A wide range of electron-deficient and -rich aryl, heterocyclic aryl, and alkyl substituents are suitable on the substrates of allylic nitriles. The regio-, enantio-, and diastereoselectivities of the reactions are excellent. As versatile platform molecules, the obtained chiral γ-azido nitriles can be easily converted into high-value-added chiral molecules that are not easily accessed by other methods. Control experiments revealed that the allylic nitrile group is important for control of the reactivity and enantioselectivity of the reaction leading to a broad substrate scope.

Antifungal Activity of Glucosinolate-Derived Nitriles and Their Synergistic Activity with Glucosinolate-Derived Isothiocyanates Distinguishes Various Taxa of Brassicaceae Endophytes and Soil Fungi.

The glucosinolates of Brassicaceae plants are converted into bioactive isothiocyanates and other volatiles during a challenge by pathogens and other biotic stressors. However, the role of alternative downstream products with weaker potency (e.g., nitriles) is far from being fully understood. This study tested the possible synergistic antifungal interaction between various glucosinolate-derived nitriles and 2-phenylethyl isothiocyanate (PEITC) on 45 fungal strains, including endophytes from horseradish roots (Brassicaceae) and soil fungi, using an airtight system enabling the accurate study of extremely volatile antifungal agents. The median minimal inhibitory concentrations (MICs) were 1.28, 6.10, 27.00 and 49.72 mM for 1H-indole-3-acetonitrile (IAN), 3-phenylpropanenitrile (PPN), 4-(methylsulfanyl)-butanenitrile (MSBN) and 3-butenenitrile (BN, = allyl cyanide), respectively. Thus, nitriles were considerably weaker antifungal agents compared to PEITC with a median MIC of 0.04 mM. For the same nitriles, the median fractional inhibitory concentration indices (FICIs) of the combinations were 0.562, 0.531, 0.562 and 0.625, respectively. Altogether, 47.7%, 56.8%, 50.0% and 27.3% of tested fungal strains showed a synergistic antifungal activity (FICI ≤ 0.5) for the nitrile-isothiocyanate combinations, respectively. Hypocreales strains showed the least sensitivity towards the GSL decomposition products and their combinations. The mean MIC values for PEITC showed 0.0679 ± 0.0358, 0.0400 ± 0.0214, 0.0319 ± 0.0087 and 0.0178 ± 0.0171 mM for Hypocreales, Eurotiales, Glomerellales and Pleosporales, respectively. In addition, nitriles, especially IAN, also showed significant differences. For the same fungi, the median FICI values fell in the ranges of 0.61-0.67, 0.52-0.61, 0.40-0.50 and 0.48-0.67, respectively, depending on the nitrile. Our results suggest that glucosinolate-derived nitriles may enhance isothiocyanate antifungal activity and that they may play an active role in shaping the plant microbiome and contribute to the filtering of microbes by plants.

Development of Catalytic Isocyanation via Precise Reactivity Control of Ambident Reagent

Isonitrile (R-NC) is a regioisomer of the corresponding nitrile (R-CN), whose C-terminus has carbene like property. Isonitriles have been deeply investigated from the viewpoint of their use. In contrast to the usability, the synthesis of isonitriles themselves are not sufficiently studied. In this manuscript, we describe our findings on catalytic nucleophilic isocyanation using cyanide with precise control of the ambident reactivity. We successfully demonstrated Pd-catalyzed allylic isocyanation. A wide variety of allylic isonitriles were obtained by this method, in high yield with good linear selectivity. Allylic nitriles were not observed at all, which were the possible side products in the reaction. Even though the reaction is the Pd-catalyzed allylic substitution, no π-allyl Pd(II) intermediate is involved in the catalytic cycle. Pd salt, such as Pd(OAc)2 and Pd(CN)2, was just the precursor of catalytic active species. It was reversibly converted into the ate complex, (Me3Si)[Pd-(CN)3], with excess amount of trimethylsilyl cyanide (Me3SiCN). The ate complex plays dual roles: 1) The Me3Si group activates phosphate leaving group on the allylation electrophile. 2) The [Pd(CN)3]- part reacts as the nucleophile with its N-terminus because the strong interaction between Pd center and C-terminus of cyanide suppresses the C-nucleophilicity. Benzylic isocyanation was successfully catalyzed by Ag2O. Both primary and secondary benzylic isonitriles were obtained in high yield. Pd-catalyzed synthesis of α-aryl-α-isocyanoacetamide derivative was also demonstrated. This catalytic procedure was appropriate to the sequential transformation into the trisubstituted oxazole without isolation of the isonitrile intermediate. Mechanistic investigations revealed that the nucleophilic isocyanation proceeded through a SN1-type substitution predominantly.

Nickel(0)‐Catalyzed Hydrocyanation of Terminal Allenes: A Regio‐ and Enantioselective Approach to Branched Allylic Nitriles

AbstractA highly branched regioselective nickel(0)‐catalyzed hydrocyanation of mono‐ and 1,1‐disubstituted allenes as well as an asymmetric hydrocyanation of 1,1‐disubstituted allenes are reported herein, giving access to branched tertiary and quaternary β,γ‐allylic nitriles. For the regioselective hydrocyanation of terminal allenes, a nickel(0)/Biphephos catalytic system applicable to a substrate scope containing functional groups such as ester, THP‐group, primary aliphatic iodide, and a free carboxylic acid, provides yields up to 96%. By applying a catalytic system of Ni(0)/TADDOL‐based bisphosphite catalyst to 1,1‐disubstituted allenes, branched quaternary allylic nitriles are obtained in yields up to 99% and enantioselectivities up to 86%. Both protocols take advantage of a manageable HCN source and evidence good atom economy. In addition, the reaction's synthesis utility is highlighted by gram‐scale reactions with subsequent assorted transformation of the nitrile group as well as alkylation of the tertiary nitriles in α‐position.magnified image

Triflamidation of Allyl-Containing Substances:Unusual Dehydrobromination vs. Intramolecular Heterocyclization.

Allyl halides with triflamide under oxidative conditions form halogen-substituted amidines. Allyl cyanide reacts with triflamide in acetonitrile or THF solutions in the presence of NBS to give the products of bromotriflamidation with a solvent interception, whereas in CH2Cl2 two regioisomers of the bromotriflamidation product without a solvent interception were obtained. The formed products undergo base-induced dehydrobromination to give linear isomers with the new C=C bond conjugated either with the nitrile group or the amidine moiety or alkoxy group. Under the same conditions, the reaction of allyl alcohol with triflamide gives rise to amidine, which was prepared earlier by the reaction of diallyl formal with triflamide. Unlike their iodo-substituted analogs, bromo-substituted amidines successfully transform into imidazolidines under the action of potassium carbonate.

Copper-catalyzed enantioselective decarboxylative cyanation of β,γ-unsaturated carboxylic acids to access chiral allyl nitriles

Copper-catalyzed asymmetric radical cyanation reactions have emerged as a powerful platform for construction of a variety of enantioenriched cyano-containing compounds under mild conditions. Herein, we report a copper-catalyzed enantioselective decarboxylative cyanation of readily available β, γ -unsaturated carboxylic acids promoted by a hypervalent iodine(III) reagent. The key allyl radical can be efficiently formed through single-electron reduction of in-situ -generated phenyliodine(III) dicarboxylates by Cu(I) species. This protocol features mild conditions, wide substrate scope, and functional group tolerance, producing a diverse range of chiral allyl nitriles in moderate to good yields and with high regio- and enantioselectivities. The enantioenriched allyl nitrile products can be used for the preparation of various synthetically useful chiral intermediates through simple transformations. • Copper-catalyzed asymmetric radical cyanation reactions are developed • Enantioselective decarboxylative cyanation of β,γ -unsaturated carboxylic acids is shown • The reaction is promoted by a hypervalent iodine(III) reagent • Efficient generation of the highly reactive allyl radical powers the reaction Copper-catalyzed asymmetric radical cyanation reactions have emerged as a powerful platform for construction of enantioenriched cyano-containing compounds under mild conditions. Zhang and Huang et al. develop a copper-catalyzed enantioselective decarboxylative cyanation of readily available β,γ-unsaturated carboxylic acids promoted by a hypervalent iodine(III) reagent.

Formation of 2D Self-Assembled Layers of Allyl Cyanide on Pd(111)

We present a mechanistic study on the interaction of allyl cyanide (AC) with Pd(111) resulting in the formation of different types of self-organized 2D layers. We employ a combination of scanning tunneling microscopy with infrared reflection absorption spectroscopy to obtain complementary information on the real space distribution of AC molecules in the self-organized 2D layers and on their chemical structure as a function of surface temperature. Specifically in the temperature range of 230–250 K, AC was found to form a self-organized 2D layer involving two different types of surface species adsorbed in trans and cis configurations. Each of these species forms identical individual (8 × 5) sublattices, which are shifted with respect to each other by three Pd atoms. Both functional groups of AC─the CN and C═C bonds─are oriented nearly parallel with respect to the metal surface. With decreasing temperature, strong changes in the layer structure were observed: the AC species agglomerate in irregular concave nonagons comprising nine molecules with the nearest AC–AC distance of three Pd atoms. These individual concave nonagons form a self-assembled 2D layer with the (13 × 10) overstructure on the extended areas of Pd(111). Below 210 K, the degree of order in the AC overlayer drastically decreases and only little structured features can be found. They comprise mainly hexagons embedded into a disordered 2D layer and some parallel rows. The nearest AC–AC distance is close to three Pd atoms in these structures. For all observed AC layers, we provide detailed atomistic-level models and accurate distances between the individual species, which were found to strongly depend on the surface temperature. With the increasing surface temperature, a noticeable increase in the characteristic distances between the interacting neighboring species was observed, which we refer to as changes in the nature of intermolecular interactions.

Radical-mediated carboselenation of terminal alkynes under mild conditions

Metal-free radical carboselenation of terminal alkynes is developed for the synthesis of (E)-γ-seleno-substituted allyl nitriles with excellent regioselectivity and stereoselectivity.

Copper-Catalyzed Enantioselective Decarboxylative Cyanation of β,γ-Unsaturated Carboxylic Acids to Access Chiral Allyl Nitriles

Copper-Catalyzed Enantioselective Decarboxylative Cyanation of β,γ-Unsaturated Carboxylic Acids to Access Chiral Allyl Nitriles

Nickel-Catalyzed Regiodivergent Cyanation of Allylic Alcohols: Scope, Mechanism, and Application to the Synthesis of 1,n-Dinitriles

Here, we report a regiodivergent cyanation of allylic alcohols under nickel catalysis. With a delicate control over the regioselectivity of allylic cyanation, more challenging branched products were successfully obtained. A variety of alkenyl nitriles and branched allylic nitriles can be synthesized. In addition, dinitriles can also be achieved from the corresponding allylic alcohols in good yields with high selectivity by a subsequent hydrocyanation process. The obtained dinitriles can easily undergo amidation or reduction or can be converted to heterocycles, piperidines, and multisubstituted pyridines. Density functional theory (DFT) calculations offered more information on the crucial role of ligands in tuning the regioselectivity and reactivity.

Competing Reaction Pathways in Heterogeneously Catalyzed Hydrogenation of Allyl Cyanide: The Chemical Nature of Surface Species.

We present a mechanistic study on the formation of an active ligand layer over Pd(111), turning the catalytic surface highly active and selective in partial hydrogenation of an α,β‐unsaturated aldehyde acrolein. Specifically, we investigate the chemical composition of a ligand layer consisting of allyl cyanide deposited on Pd(111) and its dynamic changes under the hydrogenation conditions. On pristine surface, allyl cyanide largely retains its chemical structure and forms a layer of molecular species with the CN bond oriented nearly parallel to the underlying metal. In the presence of hydrogen, the chemical composition of allyl cyanide strongly changes. At 100 K, allyl cyanide transforms to unsaturated imine species, containing the C=C and C=N double bonds. At increasing temperatures, these species undergo two competing reaction pathways. First, the C=C bond become hydrogenated and the stable N‐butylimine species are produced. In the competing pathway, the unsaturated imine reacts with hydrogen to fully hydrogenate the imine group and produce butylamine. The latter species are unstable under the hydrogenation reaction conditions and desorb from the surface, while the N‐butylimine adsorbates formed in the first reaction pathway remain adsorbed and act as an active ligand layer in selective hydrogenation of acrolein.