Zirconium-promoted epoxide rearrangement-alkynylation sequence

Additions of terminal alkynes to electrophiles are important transformations in organic chemistry. Generally, activated terminal alkynes react with epoxides in an S(N)2 fashion to form homopropargylic alcohols. We have developed a new synthetic method to form propargylic alcohols from epoxides and terminal alkynes via 1,2-shifts. This method involves cationic zirconium acetylides as both the activator of epoxides and nucleophiles. Due to the mild conditions to pre-activate alkynes with silver nitrate, this synthetic method is useful for both electron-rich and electron-deficient alkynes with other acid- and base-sensitive functional groups.     

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.     

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.     

Selective preparation of pyridines, pyridones, and iminopyridines from two different alkynes via azazirconacycles

Selective preparation of pyridine derivatives from two different alkynes and a nitrile was achieved by a novel procedure in which an alkyne and a nitrile couple first to give an azazirconacyclopentadiene followed by reaction with the second alkyne in the presence of 1 equiv of NiCl(2)(PPh(3))(2). This procedure gives only single products of pyridine derivatives from two different symmetrical alkynes and a nitrile. Our novel procedure can be used even with two similar alkyl-substituted alkynes such as 3-hexyne and 4-octyne. Two possible pyridine isomers from 3-hexyne, 4-octyne, and acetonitrile could be completely and independently prepared as single products by this method. The origin of the selectivity comes from the addition order of two different alkynes. This method was applied for the formation of pyridones and iminopyridines using isocyanate and carbodiimide derivatives instead of nitriles, respectively. Reaction of an alkyne with Cp(2)ZrEt(2) and an isocyanate or a carbodiimide gives an azazirconacycle. Treatment of the azazirconacycle with the second alkyne in the presence of 1 equiv of NiCl(2)(PPh(3))(2) gave a pyridone or an iminopyridine derivative. The use of two different unsymmetrical alkynes afforded the pyridine with five different substituents when the first alkyne has a trialkylsilyl group and the second alkyne has a phenyl group as functional groups. On the other hand, azazirconacyclopentadienes reacted with propargyl bromide in the presence of CuCl with excellent regioselectivity to give tetrasubstituted pyridine derivatives as single products. With the assistance of the trialkylsilyl groups, pyridines with all different substituents including H were also prepared.     

Ruthenium-catalyzed oxidative cleavage of alkynes to carboxylic acids

We describe an efficient method for the oxidative cleavage of alkynes to carboxylic acids using a combination of RuO(2)/Oxone/NaHCO(3) in a CH(3)CN/H(2)O/EtOAc solvent system. Both internal and terminal alkynes, regardless of their electron density, can be oxidized to carboxylic acids in excellent yield (up to 99%). (1)H NMR spectroscopy and ESI-MS experiments provided evidence for alpha-diketones and anhydrides as possible intermediates in these oxidation reactions.     

Cationic carbohydroxylation of alkenes and alkynes using the cation pool method

The reactions of an N-acyliminium ion pool with alkenes and alkynes gave gamma-amino alcohols and beta-amino carbonyl compounds, respectively, after treatment with H(2)O/Et(3)N. The present reaction serves as an efficient method for cationic carbohydroxylation of alkenes and alkynes. When vinyltrimethylsilane was used as an alkene, the reaction was highly diastereoselective and served as an access to an enantiomerically pure alpha-silyl-gamma-amino alcohol. [reaction: see text]     

Trimethylsilyl‐Protected Alkynes as Selective Cross‐Coupling Partners in Titanium‐Catalyzed [2+2+1] Pyrrole Synthesis

Trimethylsilyl (TMS)‐protected alkynes served as selective alkyne cross‐coupling partners in titanium‐catalyzed [2+2+1] pyrrole synthesis. Reactions of TMS‐protected alkynes with internal alkynes and azobenzene under the catalysis of titanium imido complexes yielded pentasubstituted 2‐TMS‐pyrroles with greater than 90 % selectivity over the other nine possible pyrrole products. The steric and electronic effects of the TMS group were both identified to play key roles in this highly selective pyrrole synthesis. This strategy provides a convenient method to synthesize multisubstituted pyrroles as well as an entry point for further pyrrole diversification through facile modification of the resulting 2‐silyl pyrrole products, as demonstrated through a short formal synthesis of the marine natural product lamellarin R.     

The application of polymer-bound carbonylcobalt(0) species in linker chemistry and catalysis

Carbonylcobalt(0) species have been used as linkers between alkynes and a polymer support for the first time. The alkynes may be loaded indirectly onto a phosphine functionalised polymer via their hexacarbonyldicobalt(0) complex, or directly onto a cobalt coated polymer. The alkynes have been released either as alkynes, thus providing a traceless method of immobilising alkynes, or by reaction with an alkene to generate a cyclopentenone via the Pauson-Khand reaction. The cobalt coated polymers produced during this study were shown to catalyse the Pauson-Khand reaction.     

Sequential intermolecular aminopalladation/ortho-arene C-H activation reactions of N-phenylpropiolamides with phthalimide

A novel palladium-catalyzed intermolecular aminopalladation/C-H activation method for selectively synthesizing (E)-(2-oxindolin-3-ylidene)phthalimides has been developed. In the presence of Pd(OAc)2 and PhI(OAc)2, alkynes were difunctionalized with a phthalimide and an arene sp2 C-H bond to selectively synthesize (E)-(2-oxoindolin-3-ylidene)phthalimides, which products are of great potential pharmaceutical value products in many major therapeutic areas, such as oncology, inflammation, neurology, immunology, and endocrinology. To the best of our knowledge, the reaction serves as the first example of intermolecular aminopalladation/C-H activation reactions of alkynes.     

Synthesis of N-(2-pyridyl)indoles via Pd(II)-catalyzed oxidative coupling

Readily available Pd(II) chloride catalysts can catalyze selective and efficient oxidative coupling between N-aryl-2-aminopyridines and internal alkynes to yield N-(2-pyridyl)indoles. This process involves the ortho C-H activation of N-aryl-2-aminopyridines, and CuCl(2) was used as an oxidant. Compared to our previously reported Rh(III)-catalyzed synthesis of this class of product, this method is advantageous with a wider scope of alkynes and cost-effective Pd(II) catalysts. Molecular oxygen can be used as a terminal oxidant.     

Copper-catalyzed aerobic intramolecular carbo- and amino-oxygenation of alkynes for synthesis of azaheterocycles

A synthetic method of highly substituted quinolines has been developed from N-(2-alkynylaryl)enamine carboxylates under Cu-catalyzed aerobic conditions via intramolecular carbo-oxygenation of alkynes. This strategy was further applied for N-alkynylamidines for amino-oxygenation of alkynes, leading to imidazole and quinazoline derivatives.     

Nickel(0)‐Catalyzed Enantioselective Annulations of Alkynes and Arylenoates Enabled by a Chiral NHC Ligand: Efficient Access to Cyclopentenones

Cyclopentenones are versatile structural motifs of natural products as well as reactive synthetic intermediates. The nickel‐catalyzed reductive [3+2] cycloaddition of α,β‐unsaturated aromatic esters and alkynes constitutes an efficient method for their synthesis. Here, nickel(0) catalysts comprising a chiral bulky C₁‐symmetric N‐heterocyclic carbene ligand were shown to enable an efficient asymmetric synthesis of cyclopentenones from mesityl enoates and internal alkynes under mild conditions. The bulky NHC ligand provided the cyclopentenone products in very high enantioselectivity and led to a regioselective incorporation of unsymmetrically substituted alkynes.     

Transition-metal-promoted or -catalyzed exocyclic alkyne insertion via zirconacyclopentene with carborane auxiliary: formation of symmetric or unsymmetric benzocarboranes

Reactions of Cp(2)Zr(μ-Cl)(μ-C(2)B(10)H(10))Li(OEt(2))(2) with alkynes R(1)C≡CR(2) gave as insertion products zirconacyclopentenes incorporating a carboranyl unit, 1,2-[Cp(2)ZrC(R(1))═C(R(2))]-1,2-C(2)B(10)H(10) (1). Treatment of 1 with another type of alkyne R(3)C≡CR(4) in the presence of stoichiometric amounts of NiCl(2) and FeCl(3) or a catalytic amount of NiCl(2) afforded symmetric or unsymmetric benzocarboranes. The regioselectivity was dominated by the polarity of the corresponding alkynes. These reactions could also be carried out in one pot, leading to the equivalent of a three-component [2 + 2 + 2] cycloaddition of carboryne and two different alkynes promoted by transition metals. A reaction mechanism was proposed after the isolation and structural characterization of the key intermediate nickelacycle. These results show that nickel complexes are more reactive than the iron ones toward the insertion of alkynes but that the latter do not initiate the trimerization of alkynes, making the insertion of activated alkynes possible. This work also demonstrates that a catalytic amount of nickel works as well as a stoichiometric amount of nickel in the presence of excess FeCl(3) for the reactions. Such a catalytic reaction may shed some light on the development of zirconocene-based catalytic reactions.     

Fast, ligand- and solvent-free synthesis of 1,4-substituted buta-1,3-diynes by Cu-catalyzed homocoupling of terminal alkynes in a ball mill

A method for the Glaser coupling reaction of alkynes by using a vibration ball mill has been developed. The procedure avoids the use of ligands and solvents during the reaction. Aryl- and alkyl-substituted terminal alkynes undergo homocoupling if coground with KF-Al(2)O(3) and CuI as a milling auxiliary and catalyst. Furthermore, an alternative protocol has been developed incorporating 1,4-diazabicyclo[2.2.2]octane (DABCO) as an additional base allowing the use of KF-Al(2)O(3) with a lower KF loading. Besides Cu salts, the homocoupling of phenylacetylene is also catalyzed by Ni or Co salts, as well as by PdCl(2). TMS-protected phenylacetylene could be directly converted into the homocoupling product after in situ deprotection of the alkyne by fluoride-initiated removal of the trimethylsilyl group.     

Hyperbaric laser chemical vapor deposition of carbon fibers from the 1-alkenes, 1-alkynes, and benzene

The growth of long carbon fibers was investigated using hyperbaric-pressure laser chemical vapor deposition (HP-LCVD). Precursors included the unbranched alkenes with linear structure 1-C(x)H(2x) (where x = 2,4,5,6,7,8), the unbranched alkynes, i.e., 1-C(x)H(2)(x-2) (where x = 3,4,5,6,8), and benzene. Rate constants, reaction orders, and apparent activation energies were derived for each precursor over a range of experimental conditions. Axial growth rates from the alkenes were 1-2 orders of magnitude greater than for the alkynes, while growth rates for benzene exceeded 10 mm s(-1). Generalized expressions for the growth rate vs molecular weight were determined. For the alkenes, the growth rate was directly proportional to the square root of the precursor molecular weight, while the alkynes exhibited an inverse relationship. Two regions of differing reaction order were identified for the alkynes; at pressures less than 2.0-2.5 bar, the average reaction order was 3.07, while above 2.0-2.5 bar, reaction orders diverged. Expressions were derived for the fraction of carbon atoms deposited per alkyne molecule transported; the deposition efficiency decreased with molecular weight for the alkynes, due in part to the Soret effect. In contrast, the reaction order for the alkenes was 1.65, and for benzene was 2.25. A phase change in the deposit was observed for both the alkenes and alkynes, with the exceptions of pentene and pentyne. Complete axial rate equations for the alkenes and alkynes were derived, as well as volumetric growth equations for the alkynes. It was shown that the volumetric rate increases nonlinearly with laser power at sufficiently high pressures.     

Synthesis of 1,1‐Diborylalkenes through a Brønsted Base Catalyzed Reaction between Terminal Alkynes and Bis(pinacolato)diboron

A method for the synthesis of 1,1‐diborylalkenes through a Brønsted base catalyzed reaction between terminal alkynes and bis(pinacolato)diboron has been developed. The procedure allows direct synthesis of functionalized 1,1‐diborylalkenes from various terminal alkynes including propiolates, propiolamides, and 2‐ethynylazoles.     

Ruthenium-catalyzed oxidative synthesis of 2-pyridones through C-H/N-H bond functionalizations

An inexpensive ruthenium catalyst enabled oxidative annulations of alkynes by acrylamides with ample scope, which allowed for the preparation of 2-pyridones employing various electron-rich and electron-deficient acrylamides as well as (di)aryl- and (di)alkyl-substituted alkynes.     

超临界二氧化碳介质中溴化钯催化炔烃环三聚反应

研究了以超临界二氧化碳为反应介质溴化钯催化炔烃环三聚反应的新方法.研究结果表明:二氧化碳介质中使用溴化钯为催化剂可以顺利地催化炔烃发生环三聚反应,区域选择性生成含苯环芳香族化合物.     

Highly efficient and diastereoselective gold(I)-catalyzed synthesis of tertiary amines from secondary amines and alkynes: substrate scope and mechanistic insights

An efficient method for the synthesis of tertiary amines through a gold(I)‐catalyzed tandem reaction of alkynes with secondary amines has been developed. In the presence of ethyl Hantzsch ester and [{(tBu)₂(o‐biphenyl)P}AuCl]/AgBF₄ (2 mol %), a variety of secondary amines bearing electron‐deficient and electron‐rich substituents and a wide range of alkynes, including terminal and internal aryl alkynes, aliphatic alkynes, and electron‐deficient alkynes, underwent a tandem reaction to afford the corresponding tertiary amines in up to 99 % yield. For indolines bearing a preexisting chiral center, their reactions with alkynes in the presence of ethyl Hantzsch ester catalyzed by [{(tBu)₂(o‐biphenyl)P}AuCl]/AgBF₄ (2 mol %) afforded tertiary amines in excellent yields and with good to excellent diastereoselectivity. All of these organic transformations can be conducted as a one‐pot reaction from simple and readily available starting materials without the need of isolation of air/moisture‐sensitive enamine intermediates, and under mild reaction conditions (mostly room temperature and mild reducing agents). Mechanistic studies by NMR spectroscopy, ESI‐MS, isotope labeling studies, and DFT calculations on this gold(I)‐catalyzed tandem reaction reveal that the first step involving a monomeric cationic gold(I)–alkyne intermediate is more likely than a gold(I)–amine intermediate, a three‐coordinate gold(I) intermediate, or a dinuclear gold(I)–alkyne intermediate. These studies also support the proposed reaction pathway, which involves a gold(I)‐coordinated enamine complex as a key intermediate for the subsequent transfer hydrogenation with a hydride source, and reveal the intrinsic stereospecific nature of these transformations observed in the experiments.     

Rhodium(I)-catalyzed [4+2+2] cycloadditions of 1,3-dienes, alkenes, and alkynes for the synthesis of cyclooctadienes

The first [4+2+2] cycloadditions involving terminal alkynes and diene-enes, including a fully intramolecular example, are reported resulting in the formation of cyclooctadienes using [RhCl(CO)2]2 (5 mol %) treated with AgSbF6 (10 mol %) as a precatalyst. The reaction is general for a variety of terminal alkynes, as well as variously substituted diene-enes (yields up to 88%).