Intra- and intermolecular reactions of indoles with alkynes catalyzed by gold

Indoles react intramolecularly with alkynes in the presence of gold catalysts to give from six- to eight-membered-ring annulated compounds. The cationic Au(I) complex [Au(P{C(6)H(4)(o-Ph)}(tBu)(2))(NCMe)]SbF(6) is the best catalyst for the formation of six- and seven-membered rings by 6-endo-dig, 6-exo-dig, and 7-exo-dig cyclizations. Indoloazocines are selectively obtained with AuCl(3) as catalyst in a rare 8-endo-dig process. In this process allenes or tetracyclic annulated derivatives are also formed as a result of an initial fragmentation reaction. The intermolecular reaction of indoles with alkynes proceeds to form 3-alkenylated intermediates that react with a second equivalent of indole to give bisindolyl derivatives. Indoles that are substituted at the 3-position react intermolecularly with alkynes to give 2-alkenylated intermediates that can be trapped intramolecularly with the appropriate nucleophiles.     

Arylcyanation of alkynes catalyzed by nickel

A nickel catalyst prepared from Ni(cod)₂ and PMe₃ is found to effect arylcyanation reaction of alkynes, namely, cleavage of a C-CN bond of an aryl cyanide followed by addition of each fragment across an alkyne. A wide range of functional groups in aryl cyanides tolerated the catalysis, giving variously functionalized β-arylalkenenitriles stereoselectively.     

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.     

Synthesis of 1(2H)-isoquinolones by the nickel-catalyzed denitrogenative alkyne insertion of 1,2,3-benzotriazin-4(3H)-ones

1,2,3-Benzotriazin-4(3H)-ones reacted with internal and terminal alkynes in the presence of a nickel(0)/phosphine catalyst to give a wide range of substituted 1(2H)-isoquinolones in high yield. The reaction proceeded through denitrogenative activation of the triazinone moiety and the following insertion of alkynes.     

Palladium-catalyzed three-component coupling of arynes with allylic acetates or halides and terminal alkynes promoted by cuprous iodide

Benzynes react with allylic acetates or halides and terminal alkynes in the presence of Pd(PPh3)4, CuI and CsF in CH3CN at 50 degrees C for 5 h to give 1-allyl-2-alkynylbenzene derivatives in good to excellent yields.     

Cyclohydrocarbonylation of substituted alkynes and tandem cyclohydrocarbonylation-CO insertion of alpha-keto alkynes catalyzed by immobilized Co-Rh heterobimetallic nanoparticles

The use of cobalt-rhodium (Co(2)Rh(2)) heterobimetallic nanoparticles in the cyclohydrocarbonylation of substituted alkynes and tandem cyclohydrocarbonylation-CO insertion of alpha-keto alkynes to give 2(3H)- or 2(5H)-furanones is described.     

Ethylenic acyl cyanides IV : Intramolecular ene cyclisation of 5-methyl-5-hexenoyl cyanides to 3-methyl-2-cyclohexenones

Condensation of methallyltrimethylsilanes with α,β-ethylenic acyl cyanides leads to 5-methyl-5-hexenoyl cyanides which after thermal cyclisation give 3-methyl-2-cyclohexenones and hydrogen cyanide.     

Copper-catalyzed complete regio- and stereoselective cyclization of 1-aryl-3-sulfanyl-4-oxahepta-1,6-diynes triggered by alkynylation

Copper(I)-catalyzed alkynylation-cyclization of 4-oxahepta-1,6-diynes 1 with a wide variety of terminal alkynes proceeded to give (3E,4Z)-3-(phenylsulfanylmethylene)-4-(2-propynylidene)tetrahydrofuran-2-yl]benzenes 2aa-he in high yields with complete regio- and stereoselectivity.     

A mechanistic investigation of the carbon-carbon bond cleavage of aryl and alkyl cyanides using a cationic RhIII silyl complex

Cationic Rh(III) complex [Cp(PMe(3))Rh(SiPh(3))(CH(2)Cl(2))]BAr(4)' (1) activates the carbon-carbon bond of aryl and alkyl cyanides (R-CN, where R = Ph, (4-(CF(3))C(6)H(4)), (4-(OMe)C(6)H(4)), Me, (i)Pr, (t)Bu) to produce complexes of the general formula [Cp*(PMe(3))Rh(R)(CNSiPh(3))]BAr(4)'. With the exception of the (t)BuCN case, every reaction proceeds at room temperature (t(1/2) < 1 h for aryl cyanides, t(1/2) < 14 h for alkyl cyanides). A general mechanism is presented on the basis of (1) an X-ray crystal structure determination of an intermediate isolated from the reaction involving 4-methoxybenzonitrile and (2) kinetic studies performed on the C-C bond cleavage of para-substituted aryl cyanides. Initial formation of an eta(1)-nitrile species is observed, followed by conversion to an eta(2)-iminoacyl intermediate, which was observed to undergo migration of R (aryl or alkyl) to rhodium to form the product [Cp*(PMe(3))Rh(R)(CNSiPh(3))]BAr(4)'.     

Some reactions of 3-halogenocinnolines catalysed by palladium compounds

3-Bromo- or 3-iodo-cinnoline (and 4-substituted analogues) are condensed with terminal alkynes in the presence of Pd and Cu compounds as catalysts to give the 3-alkynyl-derivatives. When 4-chloro- or 4-phenoxy-compounds are used, the products react with amines, in the presence of copper(I) iodide, to form pyrrolo[3,2-c]cinnolines and with hydrazines to give either the same ring system or a pyrazolo[4,3-c]cinnoline. Hydrolysis of 3-alkynyl-4-phenoxycinnoline to 3-alkynyl-4(1H)-cinnoline, followed by cyclisation, yields the furo[3,2-c]cinnoline. Attempts to condense 3-halogenocinnolines with alkenes gave variable results: 3-phenyl ethenyl- and 3(2-pyridylethenyl)-4-(1H)-cinnolinones were obtained but 3-bromocinnoline gave the 3,3′-bicinnolinyl. Action of palladium acetate in the presence of ethyl acrylate converted 3-bromo-4-phenoxycinnoline into benzofuro[3,2-c]cinnoline and 3-bromo-4-phenylaminocinnoline into indolo[3,2-c]cinnoline.     

Alkynylcyanation of alkynes and dienes catalyzed by nickel

Alkynyl cyanides are found to add across alkynes and 1,2-dienes in the presence of a catalyst prepared in situ from Ni(cod)₂, xantphos, and BPh₃. A range of functionalized conjugated cis-enynes are obtained with high regioselectivity. The addition reaction across norbornadiene proceeds in the absence of BPh₃ to give exo-cis adduct exclusively. A stoichiometric reaction of an alkynyl cyanide, Ni(cod)₂, xantphos, and BPh₃ gives trans-(xantphos)Ni(CNBPh₃)(CCSiMe₂t-Bu), which is suggested to be a plausible reaction intermediate of the alkynylcyanation reaction.     

Iron-catalyzed enyne cross-coupling reaction

In the presence of 0.5-1 mol % of FeCl(3) with lithium bromide as a crucial additive, alkynyl Grignard reagents, prepared from the corresponding alkynes and methylmagnesium bromide, react with alkenyl bromides or triflates to give the corresponding conjugated enynes in high to excellent yields. The reaction shows wide applicability to various terminal alkynes and alkenyl electrophiles.     

Bu3P-CS2加合物与含不饱和键化合物的环化反应

Bu₃P-CS₂加合物与含不饱和键化合物(富电子炔类、磷酰基炔类、磷酸基烯类)以及醛进行一锅反应以较好的收率得到1,3-二硫环戊烯或1,3-二硫环戊烷衍生物.Bu₃P-CS₂加合物与偶氮化合杨和醛类进行类似反应却得到四氢噻二唑硫酮衍生物.对反应机理进行了讨论.     

Synthetic studies in the intramolecular carbocyclization of N-acyloxyiminium ions. Stereoelectronic and steric implications of nucleophilic alkene, alkyne, and allene tethers

N-Acyloxyiminium ions generated from 4-substituted l-pyroglutamic esters with 4-(3-butenyl), 4-(3-butynyl), 4-(3-cinnamylmethyl), and 4-allenic tethers undergo rapid Lewis acid mediated carbocyclization to give stereodefined azacyclic compounds depending on the nature of the nucleophilic tether. In general, reactions of alkenes and alkynes with terminal alkyl or aryl substituents, as well as allenes, proceed through transient vinylic carbocations that are attacked internally by the N-Boc group to give tricyclic dihydrooxazinones. Diastereotopic bis-4-(3-butenyl) and 4-(3-butynyl) tethers undergo stereochemically controlled attack favoring an antiperiplanar rather than synclinal approach to give enantiopure 6-halo octahydroindole-2-carboxylic acids and 6-halo hexahydroindole-2-carboxylic acids as their methyl esters, respectively. The aza bicyclic and tricyclic compounds are excellent scaffolds for diversification.     

Rh(I)-catalyzed carbonylative cyclization reactions of alkynes with 2-bromophenylboronic acids leading to indenones

The Rh-catalyzed reaction of alkynes with 2-bromophenylboronic acids involves carbonylative cyclization to give indenones. The key steps in the reaction involve the addition of an arylrhodium(I) species to an alkyne and the oxidative addition of C-Br bonds on the adjacent phenyl ring to give vinylrhodium(I) species II. The regioselectivity depends on both the electronic and the steric nature of the substituents on the alkynes. A bulky group and an electron-withdrawing group favor the -position of indenones. In the case of silyl- or ester-substituted alkynes, the regioselectivity is extremely high. The selectivity increases in the order SiMe3 > COOR > aryl > alkyl. The reaction of norbornene with 2-bromophenylboronic acids under 1 atm of CO gives the corresponding indanone derivative. The reaction of alkynes with 2-bromophenylboronic acids under nitrogen gives naphthalene derivatives, in which two molecules of alkynes are incorporated. A vinylrhodium complex similar to II can also be generated by a different route by employing 2-bromophenyl(trimethylsilyl)acetylene and arylboronic acids in the presence of Rh(I) complex as the catalyst, resulting in the formation of indenones. The reaction of 1-(2-bromophenyl)-hept-2-yn-1-one with PhB(OH)2 in the presence of Rh(I) complex also resulted in carbonylative cyclization to give an indan-1,3-dione derivative.     

Proline-catalyzed aldol reactions of acyl cyanides with acetone: an efficient and convenient synthesis of 1,3-diketones

The aldol-type addition of acetone towards (un)substituted benzoyl, heteroarylcarbonyl or α,β-unsaturated acyl cyanides was efficiently catalyzed by l-proline (30 mol %) to give 2-hydroxy-4-oxo-2-substituted pentanenitriles. Upon the treatment with sodium hydroxide, the adducts transformed to 1,3-diketones in good-to-excellent yield, furnishing an efficient and convenient method for the regioselective synthesis of 1,3-diketones.     

Synthesis of 2,3-Dihydrothiopyran-4-ones from 3-Oxo-1-pentene-4-ynes

3-Oxo-1-pentene-4-ynes were converted with sodium sulfide or hydrogensulfide to give 2,6-disubstituted 2,3-dihydrothiopyran-4-one derivatives. The starting materials were prepared in two steps from terminal alkynes and α,β-unsaturated aldehydes.     

Synthesis of 2-boryl-1,3-butadienes from tributylphosphine stabilized zirconacyclopropenes and alkynes

Boryl zirconacycopropenes stabilized with tributylphosphine react with alkynes (terminal and internal) to give predominately 2-boryl-1,3-butadienes, 5, in 40-81% isolated yields. Products 5 are accompanied by 4-boryl-1,3-butadienes in 7-23% when terminal alkynes are inserted. However, the use of an internal alkyne (3-hexyne) gave predominantly 6c.     

Rhodium-Catalyzed Reaction of Aroyl Chlorides with Alkynes

Aroyl chlorides react with terminal alkynes accompanied by decarbonylation in the presence of a catalytic amount of [RhCl(cod)](2) and PPh(3) to give the corresponding vinyl chloride derivatives regio- and stereoselectively in good yields. The catalyst efficiency is a marked function of the ratio of PPh(3) to the rhodium species; satisfactory results are obtained by employing a PPh(3)/Rh ratio of 1.0. The reaction may involve chlororhodation to the alkynes by the intermediary arylchlororhodium(III) species generated in situ followed by reductive elimination of the products, which are suggested by the results of some control experiments. In contrast to the reaction with terminal alkynes, that with some internal ones proceeds without decarbonylation to produce 2,3-disubstituted-1-indenones as the predominant products. The product structures suggest that, while the arylchlororhodium intermediate is also involved, arylrhodation to the alkynes, reinsertion of CO (coordinated to the metal), and intramolecular cyclization sequentially take place to give the indenones.     

Synthesis of thienothiopyranthiones by a new molecular rearrangement

On heating with alkynes, the readily prepared 1,3-dithioles 3 undergo a new cycloaddition reaction and an unprecedented molecular rearrangement with loss of chlorine to give the first 7H-thieno[2,3-c]thiopyran-7-thiones 4 and 4H-thieno[3,2-c]thiopyran-4-thiones 5 whose structures were confirmed by X-ray diffraction. Unexpectedly, the different alkynes used to form 3 and to convert it into 4 and 5 were incorporated regiospecifically into the thiophene and thiopyran rings, respectively. [reaction: see text]