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.     

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.     

Iron‐Carbonyl‐Catalyzed Redox‐Neutral [4+2] Annulation of N−H Imines and Internal Alkynes by C−H Bond Activation

Stoichiometric C?H bond activation of arenes mediated by iron carbonyls was reported by Pauson as early as in 1965, yet the catalytic C?H transformations have not been developed. Herein, an iron‐catalyzed annulation of N?H imines and internal alkynes to furnish cis‐3,4‐dihydroisoquinolines is described, and represents the first iron‐carbonyl‐catalyzed C?H activation reaction of arenes. Remarkablely, this is also the first redox‐neutral [4+2] annulation of imines and alkynes proceeding by C?H activation. The reaction also features only cis stereoselectivity and excellent atom economy as neither base, nor external ligand, nor additive is required. Experimental and theoretical studies reveal an oxidative addition mechanism for C?H bond activation to afford a dinuclear ferracycle and a synergetic diiron‐promoted H‐transfer to the alkyne as the turnover‐determining step.     

Synthesis of Densely Functionalised 5‐Halogen‐1,3‐oxazin‐2‐ones by Halogen‐Mediated Regioselective Cyclisation of N‐Cbz‐Protected Propargylic Amines: A Combined Experimental and Theoretical Study

A very efficient synthesis of 5‐halogen‐1,3‐oxazin‐2‐ones has been accomplished by the halocyclisation reaction of chiral nonracemic N‐carbobenzyloxy (N‐Cbz)‐protected propargylic amines by using I₂, Br₂ and Cl₂ as electrophile sources. The nature of the halogen influences the reaction time and yield. However, in all cases the reaction is totally regioselective taking place through a 6‐endo‐dig process regardless of the nature of the halogen and of the substituents in the starting material. To rationalise the experimental results, theoretical studies at the B3LYP/6‐311G* level have been performed.     

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.     

Synthesis of 1‐silacyclopent‐2‐ene derivatives using 1,2‐hydroboration, 1,1‐organoboration and protodeborylation

The reaction of di(alkyn‐1‐yl)vinylsilanes R¹(H₂C═CH)Si(C≡C―R)₂ (R¹ = Me ( 1 ), Ph ( 2 ); R = Bu (a), Ph (b), Me₂HSi (c)) at 25°C with 1 equiv. of 9‐borabicyclo[3.3.1]nonane (9‐BBN) affords 1‐silacyclopent‐2‐ene derivatives ( 3a , 3b , 3c , 4a , 4b ), bearing one Si―C≡C―R function readily available for further transformations. These compounds are formed by consecutive 1,2‐hydroboration followed by intramolecular 1,1‐carboboration. Treated with a further equivalent of 9‐BBN in benzene they are converted at relatively high temperature (80–100°C) into 1‐alkenyl‐1‐silacyclopent‐2‐ene derivatives ( 5a , 5b 6a , 6b ) as a result of 1,2‐hydroboration of the Si―C≡C―R function. Protodeborylation of the 9‐BBN‐substituted 1‐silacyclopent‐2‐ene derivatives 3 , 4 , 5 , 6 , using acetic acid in excess, proceeds smoothly to give the novel 1‐silacyclopent‐2‐ene ( 7 , 8 , 9 , 10 ). The solution‐state structural assignment of all new compounds, i.e. di(alkyn‐1‐yl)vinylsilanes and 1‐silacyclopent‐2‐ene derivatives, was carried out using multinuclear magnetic resonance techniques (¹H, ¹³C, ¹¹B, ²⁹Si NMR). The gas phase structures of some examples were calculated and optimized by density functional theory methods (B3LYP/6‐311+G/(d,p) level of theory), and ²⁹Si NMR parameters were calculated (chemical shifts δ²⁹Si and coupling constants ⁿJ(²⁹Si,¹³C)). Copyright © 2014 John Wiley & Sons, Ltd.     

Ruthenium(II)‐Catalyzed Synthesis of Spirobenzofuranones by a Decarbonylative Annulation Reaction

The first decarbonylative insertion of an alkyne through C?H/C?C activation of six‐membered compounds is reported. The Ru‐catalyzed reaction of 3‐hydroxy‐2‐phenyl‐chromones with alkynes works most efficiently in the presence of the ligand PPh₃ to provide spiro‐indenebenzofuranones. Unlike previously reported metal‐catalyzed decarbonylative annulation reactions, in the present decarbonylative annulation reaction, the annulation occurs before extrusion of carbon monoxide.     

Well‐Defined N‐Heterocyclic Carbene‐Palladium Complexes as Efficient Catalysts for Domino Sonogashira Coupling/Cyclization Reaction and C‐H bond Arylation of Benzothiazole

Well‐defined and air‐stable PEPPSI (Pyridine Enhanced Precatalyst Preparation Stabilization and Initiation) themed palladium bis‐N‐heterocyclic carbene complexes have been developed for the domino Sonogashira coupling/cyclization reaction of 2‐iodophenol with a variety of terminal alkynes and C‐H bond arylation of benzothiazole with aryl iodides. The PEPPSI themed palladium complexes, 2a and 2b were synthesized in good yields from the reaction of corresponding imidazolium salts with PdCl₂ and K₂CO₃ in pyridine. The new air‐stable palladium‐NHC complexes were characterized by NMR spectroscopy, X‐ray crystallography, elemental analysis, and mass spectroscopy studies. The PEPPSI themed palladium(II) bis‐N‐heterocyclic carbene complexes 2a and 2b exhibited excellent catalytic activities for domino Sonogashira coupling/cyclization reaction of 2‐iodophenol with terminal alkynes yielding benzofuran derivatives. In addition, the palladium complexes, 2a and 2b successfully catalyzed the direct C‐H bond arylation of benzothiazole with aryl iodides as coupling partners in presence of CuI as co‐catalyst.     

Cobalt‐Catalyzed,Aminoquinoline‐Directed C(sp2)H Bond Alkenylation by Alkynes

A method for cobalt‐catalyzed, aminoquinoline‐ and picolinamide‐directed C(sp²)? H bond alkenylation by alkynes was developed. The method shows excellent functional‐group tolerance and both internal and terminal alkynes are competent substrates for the coupling. The reaction employs a Co(OAc)₂?4 H₂O catalyst, Mn(OAc)₂ co‐catalyst, and oxygen (from air) as a terminal oxidant.     

Cu(I)‐Catalyzed Asymmetric Cross‐Coupling of N‐Tosylhydrazones and Trialkylsilylethynes: Enantioselective Construction of C(sp)—C(sp3) Bonds

The first catalytic enantioselective C(sp)―C(sp³) cross‐coupling reaction between N‐tosylhydrazones and trialkylsilylethynes in the presence of Cu(I) salts and chiral phosphoramidite ligands was developed. A series of synthetically interesting, functionalized alkynes were obtained with moderate to good enantioselectivities (up to 83% ee). Cu(II) carbene migratory insertion is proposed to be the enantio‐determining step.     

Synthesis of Silaphenalenes by Ruthenium‐Catalyzed Annulation between 1‐Naphthylsilanes and Internal Alkynes through CH Bond Cleavage

Ruthenium‐catalyzed annulation of 1‐naphthylsilanes with internal alkynes afforded silaphenalenes through cleavage of the C?H bond at the 8‐position of the naphthalene. [RuH₂(CO){P(p‐FC₆H₄)₃}₃] efficiently catalyzed the reaction. The use of 1‐naphthyldiphenylsilane as a substrate resulted in a better yield of the annulation product compared to the use of silanes with alkyl groups on the silicon atom. Internal alkynes with both aryl and alkyl groups were tolerated in this reaction.     

Cobalt‐Catalyzed,Aminoquinoline‐Directed C(sp2)?H Bond Alkenylation by Alkynes

A method for cobalt‐catalyzed, aminoquinoline‐ and picolinamide‐directed C(sp²) H bond alkenylation by alkynes was developed. The method shows excellent functional‐group tolerance and both internal and terminal alkynes are competent substrates for the coupling. The reaction employs a Co(OAc)₂⋅4 H₂O catalyst, Mn(OAc)₂ co‐catalyst, and oxygen (from air) as a terminal oxidant.     

Surface oxidation process of a diamond‐like carbon film analyzed by difference X‐ray photoelectron spectroscopy

Difference X‐ray photoelectron spectroscopy (D‐XPS) revealed the surface oxidation process of a diamond‐like carbon (DLC) film. Evaluation of surface functional groups on DLC solely by the C 1s spectrum is difficult because the spectrum is broad and has a secondary asymmetric lineshape. D‐XPS clarified the subtle but critical changes at the DLC surface caused by wet oxidation. The hydroxyl (C―OH) group was dominant at the oxidized surface. Further oxidized carbonyl (C?O) and carboxyl (including carboxylate) (COO) groups were also obtained; however, the oxidation of C?O to COO was suppressed to some extent because the reaction required C―C bond cleavage. Wet oxidation cleaved the aliphatic hydrogenated and non‐hydrogenated sp² carbon bonds (C―H sp² and C―C sp²) to create a pair of C―OH and hydrogenated sp³ carbon (C―H sp³) bonds. The reaction yield for C―H sp² was superior at the surface, suggesting that the DLC film was hydrogen rich at the surface. Oxidation of aromatic sp² rings or polycyclic aromatic hydrocarbons such as nanographite to phenols did not occur because of their resonance stabilization with electron delocalization. Non‐hydrogenated sp³ carbon (C―C sp³) bonds were not affected by oxidation, suggesting that these bonds are chemically inert. Copyright © 2014 John Wiley & Sons, Ltd.     

Tertiary Carbinamine Synthesis by Rhodium‐Catalyzed [3+2] Annulation of N‐Unsubstituted Aromatic Ketimines and Alkynes

A convenient and waste‐free synthesis of indene‐based tertiary carbinamines by rhodium‐catalyzed imine/alkyne [3+2] annulation is described. Under the optimized conditions of 0.5–2.5 mol % [{(cod)Rh(OH)}₂] (cod=1,5‐cyclooctadiene) catalyst, 1,3‐bis(diphenylphosphanyl)propane (DPPP) ligand, in toluene at 120 °C, N‐unsubstituted aromatic ketimines and internal alkynes were coupled in a 1:1 ratio to form tertiary 1H‐inden‐1‐amines in good yields and with high selectivities over isoquinoline products. A plausible catalytic cycle involves sequential imine‐directed aromatic C? H bond activation, alkyne insertion, and a rare example of intramolecular ketimine insertion into a Rh^I–alkenyl linkage.     

Synthesis and Reactivity of 5‐Bromopenta‐2,4‐diynenitrile (BrC5N): an Access to π‐Conjugated Scaffolds

The synthesis of 5‐bromopenta‐2,4‐diynenitrile (BrC₅N) in three steps from commercially available compounds is reported. Reacting 5‐bromopenta‐2,4‐diynenitrile with secondary amines led to the formation of stable butadiynamines or enynenitriles, depending on the nature of the amine reactant. The reaction of 5‐bromopenta‐2,4‐diynenitrile with simple terminal alkynes in the presence of secondary amines, copper, and palladium catalysts, provided a straightforward access to original polyfunctional carbon‐rich scaffolds. In this work, different alkynes and secondary amines were tested, which allowed for the preparation of a family of substituted dienes. Given the high synthetic potential of 5‐bromopenta‐2,4‐diynenitrile, we also prepared iodinated counterparts of this compound, that is, 5‐iodopenta‐2,4‐diynenitrile and its lower homologue 3‐iodopropiolonitrile. The UV‐visible spectrum of some relevant compounds was also recorded.     

Enantioselective Synthesis of C−N Axially Chiral N‐Aryloxindoles by Asymmetric Rhodium‐Catalyzed Dual C−H Activation

The first enantioselective Satoh–Miura‐type reaction is reported. A variety of C?N axially chiral N‐aryloxindoles have been enantioselectively synthesized by an asymmetric rhodium‐catalyzed dual C?H activation reaction of N‐aryloxindoles and alkynes. High yields and enantioselectivities were obtained (up to 99 % yield and up to 99 % ee). To date, it is also the first example of the asymmetric synthesis of C?N axially chiral compounds by such a C?H activation strategy.     

Nickel‐Catalyzed Cyclization of ortho‐Iodoketoximes and ortho‐Iodoketimines with Alkynes: Synthesis of Highly Substituted Isoquinolines and Isoquinolinium Salts

A convenient method for the synthesis of highly substituted isoquinolines and isoquinolinium salts by the nickel‐catalyzed cyclization of ortho‐haloketoximes and ‐ketimines, respectively, with alkynes is described. The reaction of ortho‐haloketoximes and various alkynes in the presence of [Ni(PPh₃)₂Br₂] and zinc powder in a mixture of acetonitrile and tetrahydrofuran at 80 °C for 15 hours gave 1,3,4‐trisubstituted isoquinoline products in moderate to excellent yields and high regioselectivity. The corresponding isoquinoline N‐oxide was found to be the intermediate in the cyclization reaction pathway. In contrast, the reaction of ortho‐haloketimines and alkynes under similar catalytic conditions in tetrahydrofuran at 70 °C for two hours gave 1,2,3,4‐tetrasubstituted isoquinolinium salts in good to excellent yields.     

An Enantioselective Bidentate Auxiliary Directed Palladium‐Catalyzed Benzylic C−H Arylation of Amines Using a BINOL Phosphate Ligand

A new enantioselective palladium(II)‐catalyzed benzylic C?H arylation reaction of amines is enabled by the bidentate picolinamide (PA) directing group. This reaction provides the first example of enantioselective benzylic γ‐C?H arylations of alkyl amines, and proceeds with up to 97 % ee. The 2,2′‐dihydroxy‐1,1′‐binaphthyl (BINOL) phosphoric acid ligand, Cs₂CO₃, and solvent‐free conditions are essential for high enantioselectivity. Mechanistic studies suggest that multiple BINOL ligands are involved in the stereodetermining C?H palladation step.     

Vinyl polymerization of norbornene catalyzed by 2‐Py‐amidine Ni(II) complex/methylaluminoxane systems

Two 2‐Py‐amidine ligands (2‐Py―NH―C(Ph)═N―Ar, Ar = 2,6‐Me₂C₆H₃ and 2,6‐ⁱPr₂C₆H₃) and the corresponding Ni(II) complexes ( 1 and 2 ) were synthesized and characterized using elemental analysis and FT‐IR, UV–visible, ¹H NMR and ¹³C NMR spectroscopies. X‐ray crystal structures indicate that the chelate ring conformation of the less bulky complex 1 is relatively planar compared with that of the bulky complex 2 . Paramagnetic ¹H NMR and ¹³C NMR studies show that, in solution, the time‐average structures of complexes 1 and 2 have mirror symmetry. Both complexes 1 and 2 were used as catalyst precursors for norbornene polymerization with methylaluminoxane as a co‐catalyst. The effects of Al/Ni ratio, temperature and structure of precursors on the catalytic performance were investigated. Copyright © 2014 John Wiley & Sons, Ltd.     

Construction of Hexahydrophenanthrenes By Rhodium(I)‐Catalyzed Cycloisomerization of Benzylallene‐Substituted Internal Alkynes through C−H Activation

The treatment of benzylallene‐substituted internal alkynes with [RhCl(CO)₂]₂ effects a novel cycloisomerization by C(sp²)?H bond activation to produce hexahydrophenanthrene derivatives. The reaction likely proceeds through consecutive formation of a rhodabicyclo[4.3.0] intermediate, σ‐bond metathesis between the C(sp²)?H bond on the benzene ring and the C(sp²)?Rh^III bond, and isomerization between three σ‐, π‐, and σ‐allylrhodium(III) species, which was proposed based on experiments with deuterated substrates.