Aryl-Substituted Alkynes

Phenyl- and diphenylethyne have been the subject of a number of studies, no doubt because of the simplicity of the products formed, but the aromatic ring is much less reactive than the triple bond, and in most circumstances remains untouched while the triple bond is reduced. - Only occasionally has a 

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The stereochemistry of addition is usually anti for alkyl-substituted alkynes, whereas die addition to aryl-substituted compounds is not stereospecific. This suggests a termo-iecular mechanism in the alkyl case, as opposed to an aryl-stabilized vinyl cation mtermediate in the aryl case. Aryl-substituted alkynes can be shifted toward anti addition by including bromide salts in the reaction medium. Under these conditions, a species preceding the vinyl cation must be intercepted by bromide ion. This species can be presented as a complex of molecular bromine with the alkyne. An overall mechanistic summary is shown in the following scheme. 

Alkynes react with electrophilic selenium reagents such as phenylselenenyl tosylate.155 The reaction occurs with anti stereoselectivity. Aryl-substituted alkynes are regioselective, but alkyl-substituted alkynes are not. 

It has already been seen (see Section II,B and V,E) that vinylketene complexes of cobalt6,95 and chromium22 react with alkynes to produce cyclo-pentadienones, indanones, and substituted phenols. It has been shown108,109,144,145 that similar products may be derived from the alkyne adducts 247. Indeed, when alkyl or aryl substituted alkynes were reacted with vinylketene complex 221.e, a mixture of organic and organometallic products was isolated. In the cases where the alkyne is attached to an aromatic substituent, the expected alkyne adduct (247.h and 247.i) is isolated in low yield. However, when the vinylketene complex was treated... 

As most pharmaceuticals are heterocyclic, there is continuing interest in methods for the direct enantioselective construction of heterocycles. Greg Fu of reports (J. Am. Chem. Soc. 125 10778, 2003) that the addition of the dipole 1 to alkynes is catalyzed by Cul, and that in the presence of the planar-chiral ligand 2 the reaction proceeds in high enantiomeric excess. The is maintained with aryl-substituted alkynes, and is higher when there are alkyl substituents on the heterocyclic ring of 1. 

Table 1. Hydroarylation of internal aryl-substituted alkynes with mesitylene l.a...

The hydroarylation of aryl-substituted alkynes using activated AuC13 is fairly general, if electron-rich arenes are used as arylating compounds [2, 4]. Benzene or toluene do not react. Scheme 7 summarizes most of the results published on this subject. Cydization reactions using AuC13 have been reported [8], but activated forms as shown above should lead to improved yields [4],... 

Scheme 7. Scope ofthe hydroarylation reaction with aryl-substituted alkynes. Conditions ...

Internal aryl-substituted alkynes also undergo Au(111)-catalyzed hydroarylation with electron-rich alkynes (Table 1) [2, 4]. The reactivity of diphenylactylene, however, is very low. 

General Procedure for Hydroarylation of Aryl-substituted Alkynes (Small-scale Experiments)... 

The reaction has been exemplified with a variety of aryl-substituted alkynes, but it is interesting to note that a similar reaction with an epoxide-ynamide derivative 81 (Scheme 5.37), catalyzed with AgBF4, yielded the tricyclic central core 82 of gibberic acid. 

Oxetenes (oxets) have been postulated as primary photoadducts between carbonyl compounds to alkyl- and aryl-substituted alkynes and alkylthio-acetylens [66]. The first evidence for an unstable intermediate with a lifetime of several hours at — 35 °C was reported for the benzaldehyde 55/2-butyne-photoproduct 76 [67]. On further irradiation in the presence of excess benzaldehyde, a Z /s-oxetane 77 was formed (Sch. 21). 

Shim and coworkers have published several examples of the 2+2 between aryl-substituted alkynes and alkenes. Their data suggests that the singlet and triplet pathways give rise to the observed cyclobutenes. Exciplex emission was detected for the alkyne-alkene pairs. 

Not only have NHC - Pd(0) catalysts been shown to be stable under hydrogenation conditions, but they were able to hydrogenate 1-phenyl- 1-propyne with remarkable efficiency and selectivity [192], The best results were obtained with [Pd N,N -bis(2,6-diethylphenyl)imidazol-2-ylidene ] as catalyst. This complex can be efficiently formed in situ starting from [Pd(ma)(nbd)] and selectively semihydrogenated aryl-substituted alkynes to Z alkenes (Scheme 26). 

The thermal addition of alkynes to the C=S bond has been studied independently by groups headed by Behringer190191 McKinnon,192 194 Vialle,195 198 and Leaver.199-200 All have observed that the reaction between l,2-dithiole-3-thiones (7) and activated acetylenes such as aryl substituted alkynes and acetylene mono- and dicarboxylic acid esters gives rise to a mixture of 2-thioacylmethylene-l,3-dithioles (135) and l,6,6a/4-trithiapen-talenes (136). 

The Z-tail-to-tail dimers can also be obtained with high selectivity from aryl-substituted alkynes using the trisamide Ln N(SiMe3)2 3 (Ln = Y, La, Sm) [206] or the constrained-geometry catalyst system 40 [203]. The latter system is more... 

Hydroarylation can also be mediated by Au(I) and Au(III) (Scheme 33) (384). In the case of aryl substituted alkynes, the Au(III) Ji complex undergoes electrophilic aromatic substitution with the electron-rich arene to give aLkenyl-Au(III) complex, which is immediately protonated by the H generated upon C C bond formation. For the Au(I)-catalyzed hydroarylation, the cationic gold complex k coordinates the alkyne, with subsequent nucleophilic attack by the arene from the opposite face leading to an alkenyl-gold complex, which is protonated to the desired products. The nature of the reaction causes the regioselectivity of this reaction to be sensitive to electronic rather than steric factors. 

A different source of arenesulphenyl cations has been reported by Montevecchi and coworkers . They showed that the BFs-promoted reaction of 4 -nitrobenzenesulphena-nilide (35) with aryl-substituted alkynes in poorly nucleophilic solvents such as chlorobenzene generally led to bissulphides (36) and sulphimides (37) in addition to diphenyl disulphide and 4-nitroaniline. In acetonitrile as solvent, products of capture of the thiirenium ion by the solvent were also observed (equation 22). The thiirenium ion from phenylacetylene reacted even with the poorly nucleophilic solvent chlorobenzene to ( )-PhSCH=CPhC6H4Cl. With alkyl-substituted alkynes in chlorobenzene as solvent, a small amount of ( )-2-fluorovinyl sulphide PhSC(R )=CF(R ) was also detected. The yield of this sulphide could be increased when the reaction was performed in the presence of tetrabutylammonium tetrafluoroborate. Terminal alkynes gave the corresponding 2-fluorovinyl sulphides in 35-55% and internal alkynes in 65-87% yield. The procedure was unsuccessful for di-tcrt-butylacetylene and gave low yields for arylacetylenes. In acetic acid as solvent the thiirenium ion was captured as ( )-PhSC(R )=CR (OAc). 

Cycloaddition of a nitrile oxide to an alkyne generates an aromatic isoxazole directly. Monoalkyl- or -aryl-substituted alkynes lead to 5-substituted isoxazoles "" with other mono-substituted alkynes, mixtures are obtained." ... 

The scope of this asymmetric reaction is limited to aryl-substituted alkynes, and a-branched aldehydes provide the highest levels of asymmetric induction. 

Regiocontrolled net hydroboration of terminal alkynes can also be realized due to the nature of NHC-Cu complex employed. Thus, with an iV-arylated NHC (e.g., IMes or IPr), a-vinylboronates are formed, while with a bulky 7V-alkyI NHC-Cu, the p-isomer prevails. Substrates such as propargyl ethers, amines, and a variety of aryl-substituted alkynes have all been studied. ... 

The stereochemistry of addition is usualy anti for alkyl-substituted alkynes, whereas the addition to aryl-substituted compounds is not stereospecific. This suggests a termolecular mechanism in the alkyl case, as opposed to an aryl-stabilized vinyl cation intermediate in the aryl case. Aryl-substituted alkynes can be shifted... 

Shi recently reported on the Ni(ll)-catalyzed alkynylation of aromatic amides containing a (pyridine-2-yl)isopropylamine (PIP) as the directing group with ethy-nyl bromides as coupling partners (Scheme 12) [35]. When weta-substituted aromatic amides were employed, the alkynylation occurred at the sterically more accessible position. A wide variety of functional group were tolerated. The scope of the reaction with respect to ethynyl bromides was wide. Not only a triisopro-pylsilyl (TIPS) group but also a trimethylsilyl (TMS), alkyl, and aryl-substituted alkynes were applicable to the reaction. The reaction proceeded with a high catalyst turnover number (TON) of up to 196. 

B(3,5-C, H3(CF3)2)4] such that 1 mol% Ir(I) salt combined with lmol% Na[B(3,5-C 5H3(CF3)2)4] results in excellent isolated yields of the desired products [188]. Here, only arylamine substrates have been used in combination with aryl-substituted alkynes, thus the substrate scope of this system has not been fiiUy explored. 

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