Intramolecular Aminocyanation of Alkenes by N?CN Bond Cleavage

A metal‐free, Lewis acid promoted intramolecular aminocyanation of alkenes was developed. B(C₆F₅)₃ activates N‐sulfonyl cyanamides, thus leading to a formal cleavage of the N CN bonds in conjunction with vicinal addition of sulfonamide and nitrile groups across an alkene. This method enables atom‐economical access to indolines and tetrahydroquinolines in excellent yields, and provides a complementary strategy for regioselective alkene difunctionalizations with sulfonamide and nitrile groups. Labeling experiments with ¹³C suggest a fully intramolecular cyclization pattern due to the lack of label scrambling in double crossover experiments. Catalysis with Lewis acid is realized and the reaction can be conducted under air.     

Early Main Group Metal Catalysis: How Important is the Metal?

Organocalcium compounds have been reported as efficient catalysts for various alkene transformations. In contrast to transition metal catalysis, the alkenes are not activated by metal–alkene orbital interactions. Instead it is proposed that alkene activation proceeds through an electrostatic interaction with a Lewis acidic Ca²⁺. The role of the metal was evaluated by a study using the metal‐free catalysts: [Ph₂N⁻][Me₄N⁺] and [Ph₃C⁻][Me₄N⁺]. These “naked” amides and carbanions can act as catalysts in the conversion of activated double bonds (CO and CN) in the hydroamination of Ar NCO and R NCN R (R=alkyl) by Ph₂NH. For the intramolecular hydroamination of unactivated CC bonds in H₂CCHCH₂CPh₂CH₂NH₂ the presence of a metal cation is crucial. A new type of hybrid catalyst consisting of a strong organic Schwesinger base and a simple metal salt can act as catalyst for the intramolecular alkene hydroamination. The influence of the cation in catalysis is further evaluated by a DFT study.     

Early Main Group Metal Catalysis: How Important is the Metal?

Organocalcium compounds have been reported as efficient catalysts for various alkene transformations. In contrast to transition metal catalysis, the alkenes are not activated by metal–alkene orbital interactions. Instead it is proposed that alkene activation proceeds through an electrostatic interaction with a Lewis acidic Ca²⁺. The role of the metal was evaluated by a study using the metal‐free catalysts: [Ph₂N^?][Me₄N⁺] and [Ph₃C^?][Me₄N⁺]. These “naked” amides and carbanions can act as catalysts in the conversion of activated double bonds (C?O and C?N) in the hydroamination of Ar? N?C?O and R? N?C?N? R (R=alkyl) by Ph₂NH. For the intramolecular hydroamination of unactivated C?C bonds in H₂C?CHCH₂CPh₂CH₂NH₂ the presence of a metal cation is crucial. A new type of hybrid catalyst consisting of a strong organic Schwesinger base and a simple metal salt can act as catalyst for the intramolecular alkene hydroamination. The influence of the cation in catalysis is further evaluated by a DFT study.     

Copper‐Catalyzed Three‐Component Carboazidation of Alkenes with Acetonitrile and Sodium Azide

A copper‐catalyzed three‐component reaction of alkenes, acetonitrile, and sodium azide afforded γ‐azido alkyl nitriles by formation of one C(sp³)−C(sp³) bond and one C(sp³)−N bond. The transformation allows concomitant introduction of two highly versatile groups (CN and N₃) across the double bond. A sequence involving the copper‐mediated generation of a cyanomethyl radical and its subsequent addition to an alkene, and a C(sp³)−N bond formation accounted for the reaction outcome. The resulting γ‐azido alkyl nitrile can be easily converted into 1,4‐diamines, γ‐amino nitriles, γ‐azido esters, and γ‐lactams of significant synthetic value.     

Interaction between a di­methyl­amino group and an electron‐deficient alkene in ethyl (E)‐2‐cyano‐3‐(8‐di­methyl­amino­‐1‐naphthyl)­propenoate

The interaction between the peri substituents in the title compound, C₁₈H₁₈N₂O₂, measured at 150 K, represents an early stage in the addition reaction of an amino group to an electron‐deficient alkene, and has an N?Csp² separation of 2.531 (2) Å; comparison with related structures indicates that the nitrile group activates an alkene to nucleophilic attack more than a coplanar carboxyl­ic ester group.     

Catalytic Asymmetric C −H Functionalization under Photoredox Conditions by Radical Translocation and Stereocontrolled Alkene Addition

This work demonstrates how photoredox‐mediated C(sp³)?H activation through radical translocation can be combined with asymmetric catalysis. Upon irradiation with visible light, α,β‐unsaturated N‐acylpyrazoles react with N‐alkoxyphthalimides in the presence of a rhodium‐based chiral Lewis acid catalyst and the photosensitizer fac‐[Ir(ppy)₃] to provide a C?C bond‐formation product with high enantioselectivity (up to 97 % ee) and, where applicable, with some diastereoselectivity (3.0:1 d.r.). Mechanistically, the synthetic strategy exploits a radical translocation (1,5‐hydrogen transfer) from an oxygen‐centered to a carbon‐centered radical with a subsequent stereocontrolled radical alkene addition.     

Lewis Acid Catalyzed Transfer Hydromethallylation for the Construction of Quaternary Carbon Centers

The design and gram‐scale synthesis of a cyclohexa‐1,4‐diene‐based surrogate of isobutene gas is reported. Using the highly electron‐deficient Lewis acid B(C₆F₅)₃, application of this surrogate in the hydromethallylation of electron‐rich styrene derivatives provided sterically congested quaternary carbon centers. The reaction proceeds by C(sp³)?C(sp³) bond formation at a tertiary carbenium ion that is generated by alkene protonation. The possibility of two concurrent mechanisms is proposed on the basis of mechanistic experiments using a deuterated surrogate.     

Parahydrogen-Induced Polarization in Hydrogenation Reactions Mediated by a Metal-Free Catalyst

We report nuclear spin hyperpolarization of various alkenes achieved in alkyne hydrogenations with parahydrogen over a metal-free hydroborane catalyst (HCAT). Being an intramolecular frustrated Lewis pair aminoborane, HCAT utilizes a non-pairwise mechanism of H₂ transfer to alkynes that normally prevents parahydrogen-induced polarization (PHIP) from being observed. Nevertheless, the specific spin dynamics in catalytic intermediates leads to the hyperpolarization of predominantly one hydrogen in alkene. PHIP enabled the detection of important HCAT-alkyne-H₂ intermediates through substantial ¹H, ¹¹B and ¹⁵N signal enhancement and allowed advanced characterization of the catalytic process.     

Lewis Acid Coordination Redirects S‐Nitrosothiol Signaling Output

S‐Nitrosothiols (RSNOs) serve as air‐stable reservoirs for nitric oxide in biology. While copper enzymes promote NO release from RSNOs by serving as Lewis acids for intramolecular electron‐transfer, redox‐innocent Lewis acids separate these two functions to reveal the effect of coordination on structure and reactivity. The synthetic Lewis acid B(C₆F₅)₃ coordinates to the RSNO oxygen atom, leading to profound changes in the RSNO electronic structure and reactivity. Although RSNOs possess relatively negative reduction potentials, B(C₆F₅)₃ coordination increases their reduction potential by over 1 V into the physiologically accessible +0.1 V vs. NHE. Outer‐sphere chemical reduction gives the Lewis acid stabilized hyponitrite dianion trans‐[LA‐O‐N=N‐O‐LA]^2? [LA=B(C₆F₅)₃], which releases N₂O upon acidification. Mechanistic and computational studies support initial reduction to the [RSNO‐B(C₆F₅)₃] radical anion, which is susceptible to N?N coupling prior to loss of RSSR.     

A zwitterion produced by a strong intramolecular N→B interaction in 1‐hydroxy‐2‐(pyridin‐2‐ylcarbonyl)benzo[d][1,2,3]diazaborinine

2‐Acylated 2,3,1‐benzodiazaborines can display unusual structures and reactivities. The crystal structure analysis of the boron heterocycle obtained by condensing 2‐formylphenylboronic acid and picolinohydrazide reveals it to be an N→B‐chelated zwitterionic tetracycle (systematic name: 1‐hydroxy‐11‐oxo‐9,10,17λ⁵‐triaza‐1λ⁴‐boratetracyclo[8.7.0.0^2,7.0^12,17]heptadeca‐3,5,7,12,14,16‐hexaen‐17‐ylium‐1‐uide), C₁₃H₁₀BN₃O₂, produced by the intramolecular addition of the Lewis basic picolinoyl N atom of 1‐hydroxy‐2‐(pyridin‐2‐ylcarbonyl)benzo[d][1,2,3]diazaborinine to the boron heterocycle B atom acting as a Lewis acid. Neither of the other two pyridinylcarbonyl isomers (viz. nicotinoyl and isonicotinoyl) are able to adopt such a structure for geometric reasons. A favored yet reversible chelation equilibrium provides an explanation for the slow D₂O exchange observed for the OH resonance in the ¹H NMR spectrum, as well as for its unusual upfield chemical shift. Deuterium exchange may take place solely in the minor open (unchelated) species present in solution.     

Rhodium‐Catalyzed Alkene Difunctionalization with Nitrenes

The Rh^II‐catalyzed oxyamination and diamination of alkenes generate 1,2‐amino alcohols and 1,2‐diamines, respectively, in good to excellent yields and with complete regiocontrol. In the case of diamination, the intramolecular reaction provides an efficient method for the preparation of pyrrolidines, and the intermolecular reaction produces vicinal amines with orthogonal protecting groups. These alkene difunctionalizations proceed by aziridination followed by nucleophilic ring opening induced by an Rh‐bound nitrene generated in situ, details of which were uncovered by both experimental and theoretical studies. In particular, DFT calculations show that the nitrogen atom of the putative [Rh]₂=NR metallanitrene intermediate is electrophilic and support an aziridine activation pathway by N ??? N=[Rh]₂ bond formation, in addition to the N ??? [Rh]₂=NR coordination mode.     

Amidinosulphenylation of alkenes

Phenylsulphenamides react chemoselectively with an alkene and a nitrile in the presence of trifluoromethanesulphonic acid to give $\text{N}$-(β-phenylthioalkyl) amidines; in the absence of nitrile an amine is formed.Regioselective 1,2-difunctionalization of alkenes with a nitrogen nucleophile and an alkylthio^1?3 or alkylseleno^1,4 group has attracted a good deal of interest recently, because it presents a simple answer to the lack of nitrogen electrophiles capable of attacking a weak nucleophile such as an alkene.⁵ Reductive or oxidative elimination of the RS(e) group leads to overall addition to or substitution at the alkene by the nitrogen nucleophile (“N”) respectively (Scheme 1).     

Surfing π Clouds for Noncovalent Interactions: Arenes versus Alkenes

A comparative study of molecular balances by NMR spectroscopy indicates that noncovalent functional‐group interactions with an arene dominate over those with an alkene, and that a π‐facial intramolecular hydrogen bond from a hydroxy group to an arene is favored by approximately 1.2 kJ mol^?1. The strongest interaction observed in this study was with the cyano group. Analysis of the series of groups CH₂CH₃, CH?CH₂, C?CH, and C?N shows a correlation between conformational free‐energy differences and the calculated charge on the C^α atom of these substituents, which is indicative of the electrostatic nature of their π interactions. Changes in the free‐energy differences of conformers show a linear dependence on the solvent hydrogen bond acceptor parameter β.     

Solid supported Pd(0): an efficient recyclable heterogeneous catalyst for chemoselective reduction of nitroarenes

Solid supported palladium(0) (SS-Pd) catalyzed highly chemoselective reduction of nitroarenes to the corresponding anilines was accomplished under a milder reaction condition. This catalyst showed high compatibility with various reducing agents (NaBH₄, Et₃SiH, and NH₂NH₂·H₂O) and a large number of reducible functional groups such as sulfonamide, amides, carboxylic acid, ester, alcohol, halide, hetero cycle, nitrile, alkene, carbonyl, O-benzyl, and N-benzyl were tolerated. Most of the reactions were clean and high yielding. The SS-Pd catalyst could be recycled up to seven runs without significant loss of activity.     

Three derivatives of 4‐fluoro‐5‐sulfonylisoquinoline

In 4‐fluoroisoquinoline‐5‐sulfonyl chloride, C₉H₅ClFNO₂S, (I), one of the two sulfonyl O atoms lies approximately on the isoquinoline plane as a result of minimizing the steric repulsion between the chlorosulfonyl group and the neighbouring F atom. In (S)‐(−)‐4‐fluoro‐N‐(1‐hydroxypropan‐2‐yl)isoquinoline‐5‐sulfonamide, C₁₂H₁₃FN₂O₃S, (II), there are two crystallographically independent molecules (Z′ = 2). The molecular conformations of these two molecules differ in that the amine group of one forms an intramolecular bifurcated hydrogen bond with the F and OH groups, whilst the other forms only a single intramolecular N—H...F hydrogen bond. The N—H...F hydrogen bonds correspond to weak coupling between the N(H) and ¹⁹F nuclei, observed in the ¹H NMR solution‐state spectra. In (S)‐(−)‐4‐[(4‐fluoroisoquinolin‐5‐yl)sulfonyl]‐3‐methyl‐1,4‐diazepan‐1‐ium chloride, C₁₅H₁₉FN₃O₂S⁺·Cl⁻, (III), the isoquinoline plane is slightly deformed, suggestive of a steric effect induced by the bulky substituent on the sulfonyl group.     

Geometry‐Retentive C‐Alkenylation of Lithiated α‐Aminonitriles: Quaternary α‐Alkenyl Amino Acids and Hydantoins

α‐Amino nitriles tethered to alkenes through a urea linkage undergo intramolecular C‐alkenylation on treatment with base by attack of the lithionitrile derivatives on the N′‐alkenyl group. A geometry‐retentive alkene shift affords stereospecifically the E or Z isomer of the 5‐alkenyl‐4‐iminohydantoin products from the corresponding starting E ‐ or Z ‐N ′‐alkenyl urea, each of which may be formed from the same N ‐allyl precursor by stereodivergent alkene isomerization. The reaction, formally a nucleophilic substitution at an sp² carbon atom, allows the direct regioselective incorporation of mono‐, di‐, tri‐, and tetrasubstituted olefins at the α‐carbon of amino acid derivatives. The initially formed 5‐alkenyl iminohydantoins may be hydrolyzed and oxidatively deprotected to yield hydantoins and unsaturated α‐quaternary amino acids.     

Stoichiometric and Catalytic C−C and C−H Bond Formation with B(C6F5)3 via Cationic Intermediates

This work showcases a new catalytic cyclization reaction using a highly Lewis acidic borane with concomitant C−H or C−C bond formation. The activation of alkyne‐containing substrates with B(C₆F₅)₃ enabled the first catalytic intramolecular cyclizations of carboxylic acid substrates using this Lewis acid. In addition, intramolecular cyclizations of esters enable C−C bond formation as catalytic B(C₆F₅)₃ can be used to effect formal 1,5‐alkyl migrations from the ester functional groups to unsaturated carbon–carbon frameworks. This metal‐free method was used for the catalytic formation of complex dihydropyrones and isocoumarins in very good yields under relatively mild conditions with excellent atom efficiency.     

Frustrated Lewis Pairs: Metal‐free Hydrogen Activation and More

Sterically encumbered Lewis acid and Lewis base combinations do not undergo the ubiquitous neutralization reaction to form “classical” Lewis acid/Lewis base adducts. Rather, both the unquenched Lewis acidity and basicity of such sterically “frustrated Lewis pairs (FLPs)” is available to carry out unusual reactions. Typical examples of frustrated Lewis pairs are inter‐ or intramolecular combinations of bulky phosphines or amines with strongly electrophilic RB(C₆F₅)₂ components. Many examples of such frustrated Lewis pairs are able to cleave dihydrogen heterolytically. The resulting H⁺/H^? pairs (stabilized for example, in the form of the respective phosphonium cation/hydridoborate anion salts) serve as active metal‐free catalysts for the hydrogenation of, for example, bulky imines, enamines, or enol ethers. Frustrated Lewis pairs also react with alkenes, aldehydes, and a variety of other small molecules, including carbon dioxide, in cooperative three‐component reactions, offering new strategies for synthetic chemistry.     

Methylene Bridging Effect on the Structures,Lewis Acidities and Optical Properties of Semi-planar Triarylboranes

Three synthetic methods towards semi-planar triarylboranes with two aryl rings connected by a methylene bridge have been developed. The fine-tuning of their stereoelectronic properties and Lewis acidities was achieved by introducing fluorine, methyl, methoxy, n-butyl and phenyl groups either at their exocyclic or bridged aryl rings. X-ray diffraction analysis and quantum-chemical calculations provided quantitative information on the structural distortion experienced by the near planar hydro-boraanthracene skeleton during the association with Lewis bases such as NH₃ and F⁻. Though the methylene bridge between the ortho-positions of two aryl rings of triarylboranes decreased the Gibbs free energies of complexation with small Lewis bases by less than 5 kJ mol⁻¹ relative to the classical Lewis acid BAr₃, the steric shielding of the CH₂ bridge is sufficient to avoid the formation of Lewis adducts with larger Lewis bases such as triarylphosphines. A newly synthesized spirocyclic amino-borane with a long intramolecular B−N bond that could be dissociated under thermal process, UV-irradiation, or acidic conditions might be a potential candidate in Lewis pairs catalysis.     

Metal‐to‐Ligand Alkyl Migration Inducing Carbon–Sulfur Bond Cleavage in Dialkyl Yttrium Complexes Supported by Thiazole‐Containing Amidopyridinate Ligands: Synthesis,Characterization, and Catalytic Activity in the Intramolecular Hydroamination Reaction

Neutral Y^III dialkyl complexes supported by tridentate N^?,N,N monoanionic methylthiazole– or benzothiazole–amidopyridinate ligands have been prepared and completely characterized. Studies on their stability in solution revealed progressive rearrangement of the coordination sphere in the benzothiazole‐containing system through an unprecedented metal‐to‐ligand alkyl migration and subsequent thiazole ring opening. Attempts to synthesize hydrido species from the dialkyl precursor led to the generation of a dimeric yttrium species stabilized by a trianionic N^?,N,N^?,S^? ligand as the result of metal‐to‐ligand hydride migration with chemoselective thiazole ring opening and subsequent dimerization through intermolecular addition of the residual Y?H group to the imino fragment of a second equivalent of the ring‐opened intermediate. DFT calculations were used to elucidate the thermodynamics and kinetics of the process, in support of the experimental evidence. Finally, all isolated yttrium complexes, especially their cationic forms prepared by activation with the Lewis acid Ph₃C⁺[B(C₆F₅)₄]^?, were found to be good candidate catalysts for intramolecular hydroamination/cyclization reactions. Their catalytic performance with a number of primary and secondary amino alkenes was assessed.