Manganese‐Catalyzed Dehydrogenative [4+2] Annulation of NH Imines and Alkynes by CH/NH Activation

Described herein is a manganese‐catalyzed dehydrogenative [4+2] annulation of N? H imines and alkynes, a reaction providing highly atom‐economical access to diverse isoquinolines. This transformation represents the first example of manganese‐catalyzed C? H activation of imines; the stoichiometric variant of the cyclomanganation was reported in 1971. The redox neutral reaction produces H₂ as the major byproduct and eliminates the need for any oxidants, external ligands, or additives, thus standing out from known isoquinoline synthesis by transition‐metal‐catalyzed C? H activation. Mechanistic studies revealed the five‐membered manganacycle and manganese hydride species as key reaction intermediates in the catalytic cycle.     

Degenerate rearrangement of 9-isopropenyl-9,10-dimethyl-phenanthren-9-yl and 9,10-dimethyl-9-(trans-1-methylprop-1-en-1-yl)phenanthren-9-yl cations

¹H NMR study has shown that long-lived 9-R-9,10-dimethylphenanthren-9-yl cations (R = isopropenyl, trans-1-methylprop-1-en-1-yl) generated in the system HSO₃F-SO₂ClF-CD₂Cl₂ at ?130°C undergo degenerate rearrangement via 1,2-vinyl shifts (ΔG’ = 37 and 39 kJ/mol, respectively, at ?88°C). Analysis of the geometric parameters of the initial structures and transition states calculated by the DFT method indicates that unfavorable steric factors are responsible for the sharp deceleration of 1,2-shifts of the isopropenyl and trans-1-methylprop-1-en-1-yl groups as compared to vinyl and cis-1-methylprop-1-en-1-yl groups, respectively.     

2,4‐Dinitrophenol‐Catalyzed α‐C(sp3)−H and C(sp)−H Bond Functionalization of Cyclic Amines and Alkynes: Highly Regio‐/Diastereoselective Synthesis of α‐Alkynyl‐3‐Amino‐2‐Oxindoles

A transition‐metal‐ and oxidant‐free DNP (2,4‐dinitrophenol)‐catalyzed atom‐economical regio‐ and diastereoselective synthesis of monofunctionalized α‐alkynyl‐3‐amino‐2‐oxindole derivatives by C?H bond functionalization of cyclic amines and alkynes with indoline‐2,3‐diones has been developed. This cascade event sequentially involves the reductive amination of indoline‐2,3‐dione by imine formation and cross coupling between C(sp³)?H and C(sp)?H of the cyclic amines and alkynes. This reaction offers an efficient and attractive pathway to different types of α‐alkynyl‐3‐amino‐2‐oxindole derivatives in good yields with a wide tolerance of functional groups. The salient feature of this methodology is that it completely suppresses the homocoupling of alkynes. To the best of our knowledge, this is the first example of a DNP‐catalyzed metal‐free direct C(sp³)?H and C(sp)?H bond functionalization providing biologically active α‐alkynyl‐3‐amino‐2‐oxindole scaffolds.     

Reactivity Studies of Iridium Pyridylidenes [TpMe2Ir(C6H5)2(C(CH)3C(R)NH] (R=H,Me, Ph)

The reactivity of a series of iridium? pyridylidene complexes with the formula [Tp^Me2Ir(C₆H₅)₂(C(CH)₃C(R)N H] ( 1 a – 1 c ) towards a variety of substrates, from small molecules, such as H₂, O₂, carbon oxides, and formaldehyde, to alkenes and alkynes, is described. Most of the observed reactivity is best explained by invoking 16 e^? unsaturated [Tp^Me2Ir(phenyl)(pyridyl)] intermediates, which behave as internal frustrated Lewis pairs (FLPs). H₂ is heterolytically split to give hydride? pyridylidene complexes, whilst CO, CO₂, and H₂C?O provide carbonyl, carbonate, and alkoxide species, respectively. Ethylene and propene form five‐membered metallacycles with an IrCH₂CH(R)N (R=H, Me) motif, whereas, in contrast, acetylene affords four‐membered iridacycles with the IrC(?CH₂)N moiety. C₆H₅(C?O)H and C₆H₅C?CH react with formation of Ir? C₆H₅ and Ir? C?CPh bonds and the concomitant elimination of a molecule of pyridine and benzene, respectively. Finally the reactivity of compounds 1 a – 1 c against O₂ is described. Density functional theory calculations that provide theoretical support for these experimental observations are also reported.     

RhIII‐Catalyzed C?H Activation: A Versatile Route towards Various Polycyclic Pyridinium Salts

An efficient and convenient method for the synthesis of highly substituted polycyclic pyridinium salts from the reaction of various 2‐aryl‐pyridines and 2‐aryl‐sp²‐nitrogen‐atom‐containing heterocycles with alkynes through rhodium(III)‐catalyzed C? H activation and annulation under an O₂ atmosphere is described. A possible mechanism that involves the chelation‐assisted C? H activation of the 2‐aryl‐pyridine substrate, insertion of the alkyne, and reductive elimination is proposed. This mechanism was supported by the isolation of a five‐membered rhodacycle ( I′ ). In addition, kinetic isotope studies were performed to understand the intimate reaction mechanism.     

Exploring Bis(cyclometalated) Ruthenium(II) Complexes as Active Catalyst Precursors: Room‐Temperature Alkene–Alkyne Coupling for 1,3‐Diene Synthesis

Described is the development of a new class of bis(cyclometalated) ruthenium(II) catalyst precursors for C? C coupling reactions between alkene and alkyne substrates. The complex [(cod)Ru(3‐methallyl)₂] reacts with benzophenone imine or benzophenone in a 1:2 ratio to form bis(cyclometalated) ruthenium(II) complexes ( 1 ). The imine‐ligated complex 1 a promoted room‐temperature coupling between acrylic esters and amides with internal alkynes to form 1,3‐diene products. A proposed catalytic cycle involves C? C bond formation by oxidative cyclization, β‐hydride elimination, and C? H bond reductive elimination. This Ru^II/Ru^IV pathway is consistent with the observed catalytic reactivity of 1 a for mild tail‐to‐tail methyl acrylate dimerization and for cyclobutene formation by [2+2] norbornene/alkyne cycloaddition.     

Synthesis, spectroscopy and electronic structure of the vinylidene and alkynyl complexes [W(C=CHR)(dppe)(η-C₇H₇)](+) and [W(C≡CR)(dppe)(η-C₇H₇](n+) (n = 0 or 1)

The first examples of vinylidene complexes of the cycloheptatrienyl tungsten system [W(C=CHR)(dppe)(η-C?H?)](+) (dppe = Ph?PCH?CH?PPh?; R = H, 3; Ph, 4; C?H?-4-Me, 5) have been synthesised by reaction of [WBr(dppe)(η-C?H?)], 1, with terminal alkynes HC≡CR; a one-pot synthesis of 1 from [WBr(CO)?(η-C?H?)] facilitates its use as a precursor. The X-ray structure of 4[PF?] reveals that the vinylidene ligand substituents lie in the pseudo mirror plane of the W(dppe)(η-C?H?) auxiliary (vertical orientation) with the phenyl group located syn to the cycloheptatrienyl ring. Variable temperature 1H NMR investigations on [W(C=CH?)(dppe)(η-C?H?)][PF?], 3, estimate the energy barrier to rotation about the W=C(α) bond as 62.5 ± 2 kJ mol?1; approximately 10 kJ mol?1 greater than for the molybdenum analogue. Deprotonation of 4 and 5 with KOBu(t) yields the alkynyls [W(C≡CR)(dppe)(η-C?H?)] (R = Ph, 6; C?H?-4-Me, 7) which undergo a reversible one-electron oxidation at a glassy carbon electrode in CH?Cl? with E(?) values approximately 0.12 V negative of Mo analogues. The 17-electron radicals [6](+) and [7](+) have been investigated by spectroelectrochemical IR, UV-visible and EPR methods. The electronic structures of representative vinylidene (3) and alkynyl (6) complexes have been investigated at the B3LYP/Def2-SVP level. In both cases, electronic structure is characterised by a frontier orbital with significant metal d(z2)character and this dominates the structural and spectroscopic properties of the system.     

Synthesis of indoles with a polyfluorinated benzene ring

A two-step sequence consisting of a Sonogashira coupling of polyfluorinated 2-iodoanilines with terminal alkynes, followed by a KOH promoted cyclization of the 2-alkynylanilines thus formed, has been developed as a one-pot synthesis of 2-R-indoles (R=n-Bu, Ph, CH₂OTHP→CH₂OH, C(CH₃)₂OH→H) containing a polyfluorinated benzene moiety.     

Nickel‐catalyzed three‐component coupling reaction of terminal alkynes,dihalomethane and amines to propargylamines

Direct C―H and C―halogen activation is an important and practical task in C―C, C―N bond formation reactions using alkynes. Propargylic amines are synthetically versatile intermediates for the preparation of many nitrogen‐containing biologically active motifs. Herein, a 15 mol% Ni(py)₄Cl₂/bipyridine‐catalyzed three‐component coupling reaction of alkynes, halomethane and amines through C―H and C―halogen activation was developed for the facile synthesis of propargylic amines. Tetramethylguanidine shows excellent basicity in acetonitrile and works under mild conditions. The reaction has very good functional group tolerance to aliphatic and aromatic alkynes. Copyright © 2013 John Wiley & Sons, Ltd.     

Activation of CH bonds in acetylene and terminal alkynes by rhodium(I) species. Crystal structure of cis-(ethynyl)hydride [(NP3)Rh(H)(CCH)]BPh4·1.5C4H8O (NP3 = N(CH2CH2PPh2)3)

The 16-electron fragment (NP₃)Rh⁺ inserts in a highly stereospecific manner across CH bonds from acetylene and 1-alkynes to give the octahedral cis-(alkynyl)hydrides [(NP₃)Rh(H)(CCR)]BPh₄ (R = H, Ph, COOEt). The structure of the cis-(ethynyl)hydride [(NP₃)Rh(H)(CCH)]BPh₄ · 1.5 THF has been established by X-ray diffraction. The trigonal bipyramidal rhodium(I) complex [(NP₃)RhH], reacts with terminal alkynes to give H₂ and the neutral σ-acetylides [(NP₃)Rh(CCR)] (R = Ph, COOEt). These undergo metathesis between terminal alkynes and the σ-acetylide ligand through a mechanism involving consecutive breaking and making of CH bonds.     

On the Redox Properties of Cyclophosphanes

Abstract

While sulfur rings form stable, isolable dications, corresponding dications of cyclophosphanes are not known so far. Here we report on the electrochemical formation of the mono- and dication of 1 (R?N(i-propyl)₂). The monocation of 1 is a stable species, even at room temperature. On the contrary the corresponding dication rearranges under a sequence of fast 1.2-shifts of the substituents, even at temperatures below ?80°C to intermediary ‘carbene-like’ structures, which finally fragment into the diamino-phosphenium cation, 3, and P₂ (which subsequently polymerizes). Quantum chemical investigations are in support of these findings and suggest a general model for the redox properties of cyclophosphanes.     

Palladium‐Catalyzed Carbonylative [3+2+1] Annulation of N‐Aryl‐Pyridine‐2‐Amines with Internal Alkynes by CH Activation: Facile Synthesis of 2‐Quinolinones

We describe here a novel procedure for the synthesis of highly substituted 2‐quinolinones. By this newly developed approach, 2‐quinolinone derivatives were prepared in moderate to good yields by carbonylative cyclization of N‐aryl‐pyridine‐2‐amines and internal alkynes by C?H activation. Remarkably, [Mo(CO)₆] was applied as a solid CO source and the reaction proceeded in an atom economic manner.     

Rhodium(III)‐Catalyzed [3+2] Annulation of 5‐Aryl‐2,3‐dihydro‐1H‐pyrroles with Internal Alkynes through C(sp2)H/Alkene Functionalization

This study describes a new rhodium(III)‐catalyzed [3+2] annulation of 5‐aryl‐2,3‐dihydro‐1H‐pyrroles with internal alkynes using a Cu(OAc)₂ oxidant for building a spirocyclic ring system, which includes the functionalization of an aryl C(sp²)? H bond and addition/protonolysis of an alkene C?C bond. This method is applicable to a wide range of 5‐aryl‐2,3‐dihydro‐1H‐pyrroles and internal alkynes, and results in the assembly of the spiro[indene‐1,2′‐pyrrolidine] architectures in good yields with excellent regioselectivities.     

A Sequential Homologation of Alkynes and Aldehydes for Chain Elongation with Optional 13C‐Labeling

Terminal alkynes (RCCH) are homologated by a sequence of ruthenium‐catalyzed anti‐Markovnikov hydration of alkyne to aldehyde (RCH₂CHO), followed by Bestmann–Ohira alkynylation of aldehyde to chain‐elongated alkyne (RCH₂CCH). Inverting the sequence by starting from aldehyde brings about the reciprocal homologation of aldehydes instead. The use of ¹³C‐labeled Bestmann–Ohira reagent (dimethyl ((1‐¹³C)‐1‐diazo‐2‐oxopropyl)phosphonate) for alkynylation provides straightforward access to singly or, through additional homologation, multiply ¹³C‐labeled alkynes. The labeled alkynes serve as synthetic platform for accessing a multitude of specifically ¹³C‐labeled products. Terminal alkynes with one or two ¹³C‐labels in the alkyne unit have been submitted to alkyne–azide click reactions; the copper‐catalyzed version (CuAAC) was found to display a regioselectivity of >50 000:1 for the 1,4‐ over the 1,5‐triazine isomer, as shown analytically by ¹³C NMR spectroscopy.     

A Biomimetic Catalytic Aerobic Functionalization of Phenols

The importance of aromatic C? O, C? N, and C? S bonds necessitates increasingly efficient strategies for their formation. Herein, we report a biomimetic approach that converts phenolic C? H bonds into C? O, C? N, and C? S bonds at the sole expense of reducing dioxygen (O₂) to water (H₂O). Our method hinges on a regio‐ and chemoselective copper‐catalyzed aerobic oxygenation to provide ortho‐quinones. ortho‐Quinones are versatile intermediates, whose direct catalytic aerobic synthesis from phenols enables a mild and efficient means of synthesizing polyfunctional aromatic rings.     

Selective Hydrosilylation of Alkynes with Octaspherosilicate (HSiMe2O)8Si8O12

Comprehensive studies on platinum‐catalyzed hydrosilylation of a wide range of terminal and internal alkynes with spherosilicate (HSiMe₂O)₈Si₈O₁₂ ( 1 a ) were performed. The influence of the reaction parameters and the types of reagents and catalysts on the efficiency of the process, which enabled the creation of a versatile and selective method to synthesize olefin octafunctionalized octaspherosilicates, was studied in detail. Within this work, twenty novel 1,2‐(E)‐disubstituted and 1,1,2‐(E)‐trisubstituted alkenyl‐octaspherosilicates ( 3 a – m , 6 n – t ) were selectively obtained with high yields, and fully characterized (¹H, ¹³C, ²⁹Si NMR, FTIR, MALDI TOF or TOF MS ES⁺ analysis). Moreover, the molecular structure of the compound (Me₃Si(H)C=C(H)SiMe₂O)₈Si₈O₁₂ ( 3 a ) was determined by X‐ray crystallography for the first time. The developed procedures are the first that allow selective hydrosilylation of terminal silyl, germyl, aryl, and alkyl alkynes with 1 a , as well as the direct introduction of sixteen functional groups into the 1 a structure by the hydrosilylation of internal alkynes. This method constituted a powerful tool for the synthesis of hyperbranched compounds with a Si?O based cubic core. The resulting products, owing to their unique structure and physicochemical properties, are considered novel, multifunctional, hybrid, and nanometric building blocks, intended for the synthesis of star‐shaped molecules or macromolecules, as well as nanofillers and polymer modifiers. In the presented syntheses, commercially available reagents and catalysts were used, so these methods can be easily repeated, rapidly scaled up, and widely applied.     

Amidines for Versatile Ruthenium(II)‐Catalyzed Oxidative CH Activations with Internal Alkynes and Acrylates

Cationic ruthenium complexes derived from KPF₆ or AgOAc enabled efficient oxidative C?H functionalizations on aryl and heteroaryl amidines. Thus, oxidative annulations of diversely decorated internal alkynes provided expedient access to 1‐aminoisoquinolines, while catalyzed C?H activations with substituted acrylates gave rise to structurally novel 1‐iminoisoindolines. The powerful ruthenium(II) catalysts displayed a remarkably high site‐, regio‐ and, chemoselectivity. Therefore, the catalytic system proved tolerant of a variety of important electrophilic functional groups. Detailed mechanistic studies provided strong support for the cationic ruthenium(II) catalysts to operate by a facile, reversible C?H activation.     

O-Protonation of α-Diazoketones in Super-strong Acids

Primary diazoketones, R? CO? CHN₂, are O-protonated in HF? SbF₅? SO₂ or FSO₃H? SbF₅? SO₂ at ?60°, as observed by NMR. The OH-proton resonates at 9.3–9.6 δ and is coupled with H? C 1 (J = 1–2.5 Hz). Secondary diazoketones, R? CO? C(N₂)? R, when protonated, give an OH-singlet at 8.85 δ. The assignments are corroborated by use of deuterated diazoketones, R? CO? CDN₂, or deuterated acid, FSO₃D. Primary diazoketones react with FSO₃H at ?60° to ?15°, giving products assigned the fluorosulfate structure, R? CO? CH₂? OSO₂F; they do not exchange H? C 1 with solvent before or during decomposition. Intermediate C-protonated diazonium ions and α-oxo-carbonium ions (vinyl carbonium ions) have not been identified. 3-Diazo-4-methyl-2-pentanone (VIII) reacts with FSO₃H at ?15°, eliminating N₂ and giving protonated mesityl oxide by a strictly intramolecular hydride shift.     

Thermal [1,5] sigmatropic rearrangements in (σ-7-cycloheptatrienyl)triphenyltin and (σ-5-cyclohepta-1,3-dienyl)triphenyltin: A 1H and 13C NMR reinvestigation

It has been confirmed by ¹H and ¹³C NMR spectroscopies that Sn(σ-C₇H₇)Ph₃ undergoes either 1,4- or 1,5-shifts of the SnPh₃ moiety around the cycloheptatrienyl ring with ΔH³ = 13.8 ± 0.4 kcal mol^?1, ΔS3 = ?5.6 ± 1.2 cal mol^?1 deg^?1, and ΔG³₃₀₀ = 15.44 ± 0.14 kcal mol^?1. Similarly, (σ-5-cyclohepta-1,3-dienyl)triphenyltin undergoes 1,5-shifts with ΔH³ = 12.4 ± 0.6 kcal mol^?1, ΔS³ = ?11.2 ± 1.8 cal mol^?1 deg^?1, and ΔG³₃₀₀ = 15.76 ± 0.13 kcal mol^?1. It is therefore probable that Sn(σ-5-C₅H₅)R₃ and Sn(σ-3-indenyl)R₃ do not undergo 1,2-shifts as previously suggested but really undergo 1,5-shifts.     

Gold‐Catalyzed C(sp3)H/C(sp)H Coupling/Cyclization/Oxidative Alkynylation Sequence: A Powerful Strategy for the Synthesis of 3‐Alkynyl Polysubstituted Furans

In sharp contrast to the gold‐catalyzed reactions of alkynes/allenes with nucleophiles, gold‐catalyzed oxidative cross‐couplings and especially C? H/C? H cross‐coupling have been under represented. By taking advantage of the unique redox property and carbophilic π acidity of gold, this work realizes the first gold‐catalyzed direct C(sp³)? H alkynylation of 1,3‐dicarbonyl compounds with terminal alkynes under mild reaction conditions, with subsequent cyclization and in situ oxidative alkynylation. A variety of terminal alkynes including aryl, heteroaryl, alkenyl, alkynyl, alkyl, and cyclopropyl alkynes all successfully participate in the domino reaction. The protocol offers a simple and region‐defined approach to 3‐alkynyl polysubstituted furans.