Disubstituted alkyne

The formation of disubstituted alkynes by coupling of terminal alkynes, followed by intramolecular attack of an alcohol or amine, is used for the preparation of benzofurans and indoles. The benzo[il)]furan 356 can be prepared easily by the reaction of o-iodophenol with a terminal alkyne[262]. The 2-substituted indole 358 is prepared by the coupling of 2-ethynylaniline (357) with aryl and alkenyl halides or triflates, followed by Pd(ll)-catalyzed cycliza-tion[263]. 

Interesting formation of the fulvene 422 takes place by the reaction of the alkenyl bromide 421 with a disubstituted alkyne[288]. The indenone 425 is prepared by the reaction of o-iodobenzaldehyde (423) with internal alkyne. The intermediate 424 is formed by oxidative addition of the C—H bond of the aldehyde and its reductive elimination affords the enone 425(289,290]. 

Hydrocarbons that contain a carbon-carbon triple bond are called alkynes Non cyclic alkynes have the molecular formula C H2 -2 Acetylene (HC=CH) is the simplest alkyne We call compounds that have their triple bond at the end of a carbon chain (RC=CH) monosubstituted or terminal alkynes Disubstituted alkynes (RC=CR ) have internal triple bonds You will see m this chapter that a carbon-carbon triple bond is a functional group reacting with many of the same reagents that react with the double bonds of alkenes... 

By using a cocatalyst of Pd-Cu, aryl-alkenyl halides couple efficiently widi alkynes to generate die disubstituted alkynes (Scheme 9.6).8 This coupling reaction has been applied to die synthesis of polyphenyleneethynylenes by Yamamoto et al. in 1984 (Scheme 9.7).9a Due to the ready availability of diacetylenes and the mild coupling condition, this strategy has been widely used for die preparation of many poly(aryleneethynylene)s.9... 

The stoichiometric hydroamination of unsymmetrically disubstituted alkynes is highly regioselective, generating the azametaUacycle with the larger alkyne substituent a to the metal center [294, 295]. In others words, the enamine or imine formed results from an anti-Markovnikov addition. Unfortunately, this reaction could not be applied to less stericaUy hindered amines. 

For unsymmetrically disubstituted alkynes, the regioselectivity is 100% anti-Markovnikov, phenylpropyne being the most reactive alkyne (Eq. 4.78) [296]. 

Scheme 8-20 Regio- and stereo-selectivity of the hydrozirconation of disubstituted alkynes...

It is interesting to note that a copper(II)-mediated coupling reaction of alkenyldialkyl- or trialkylboranes with alkynylcopper compounds, generated in situ, in the presence of various solvents and a small amount of water, gives (E)-l,3-enynes (or disubstituted alkynes) with various functional groups in reasonable yields (Eq. 4.3).12... 

Alternatively, l,3-dithiol-2-ones have been obtained by reacting di-isopropylxanthogen disulfide with unsaturated substrates, such as disubstituted alkynes R2C2, in the presence of AIBN (azoisobutyrylnitrile), a radical initiator.78 Finally, vinylene dithiocarbonates can be obtained by reacting mer-cury(II) acetate with the corresponding trithiocarbonates, generated by reaction of electrophilic alkynes with ethylene trithiocarbonate.79 Analogously,... 

The cycloaddition-isomerization procedure can be accomplished in the presence of a catalytic amount of a transition metal salt. The reactions proceed at room temperature, neither air nor water needed to be excluded. The presence of an electron-withdrawing group is not necessary to activate the dienophile as the example below shows that gold coordination increases the electrophilicity of the triple bond. The presence of a terminal alkyne should also be important. In the case of a disubstituted alkyne no reaction can be observed <00JA11553>. 

A highly regio- and stereo-regulated synthesis of the (Z)-l,4-benzodioxepin-5-ones 115 (Ar = Ph, 4-MeOC6H4 X = 0) has been reported, and involved, at the penultimate stage, cyclization of disubstituted alkynes on treatment with copper (I) iodide. <00JCS(P1)775>. 

Indoles can be formed by metal-catalyzed cyclizations of azobenzenes on disubstituted alkynes (Equation (106)). 

A similar coupling reaction of salicyl aldehydes with disubstituted alkynes, catalyzed by rhodium, is known... 

Garbazoles are also synthesized by a concomitant Pd migration/cross-coupling process involving the coupling of A-(3-iodophenyl)anilines with disubstituted alkynes (Equation (158)).1... 

In the reaction of disubstituted alkynes, 1,3-migration of the acetate takes place to give allenyl esters that can be versatile substrates, especially for [3,3]-Cope rearrangements.333 1,5-Enynes have proved to be versatile substrates for the preparation of perfumery agents such as sabinol334 and sabina ketone.335 Transannular systems undergo similar reactions.336... 

Gycloisomerization of a disubstituted alkyne sometimes required activation of the alkyne by the addition of a conjugated carbonyl and performing the reaction at a higher temperature as in Equation (38). The geometry of the alkene determines the regioselectivity of the /3-hydride elimination, as ( )-60 gave predominantly 61 (Equation (38)), while 62 was the major product of the cycloisomerization of (Z)-60 (Equation (39)). 

The metal-mediated and metal-catalyzed [6 + 2]- and [6 + 4]-cycloaddition reactions, pioneered by Pettit and co-workers105 106 and Kreiter and co-workers,107 respectively, involve the cycloaddition of metal-complexed cyclic trienes with 7r-systems such as alkenes, alkynes, and dienes. The [6 + 2]-reactions produce bicyclo[4.2.1]nonadiene derivatives and the [6 + 4]-reactions produce bicyclo[4.4.1]undecatrienes (Scheme 32). Trienes complexed to chromium, which can be prepared on large scale (40 g) as reported by Rigby and co-workers,108 react with 7r-systems upon thermolysis or irradiation.109-111 Chromium and iron-catalyzed [6 + 2]-reactions of cycloheptatrienes and disubstituted alkynes... 

Although disubstituted alkynes are used successfully as two-carbon components in chromium-mediated and -catalyzed [6 + 2]-reactions, the use of terminal alkynes produces a [6 + 2 + 2]-reaction (Section 10.13.3.7). Buono and co-workers have discovered that when a cobalt catalyst is employed, several monosubstituted alkynes can be used in [6 + 2]-cycloadditions with cycloheptatriene (Scheme 35). The use of a chiral BINOL-phosphoramidite cobalt complex affords an enantioselective [6 + 2]-cycloaddition reaction (Equation (18)).121... 

The whole situation changes slightly when the substrate contains a disubstituted alkyne 58 (Scheme 1.25). Then often no or only an incomplete or very slow isomerization is observed without a base. For example, a methyl substitution of the alkyne slows the reaction about 300-fold compared with the terminal alkyne [115]. However, with the base again high yields of the isomerization product 59 are obtained [116— 121]. A substituent a to the carbonyl group seems to have a similar effect [122]. 

Disubstituted alkynes and terminal alkynes form E-dibromoalkenes [4] when the tribromide is formed in situ in an essentially basic medium, an addition reaction followed by elimination of hydrogen bromide results in the conversion of terminal alkynes into the 1-bromoalkynes [5]. When the addition reaction is conducted in methanol, l,l-dibromo-2,2-dimethoxyalkanes are produced, in addition to the 1,2-dibromoalkenes [6], The dimethoxy compounds probably result from the initial intermediate formation of bromomethoxyalkenes. Under similar conditions, alkenes yield methoxy bromo compounds [7]. 

Thiols react directly with non-activated alkynes [15] and with 1-alkynyl thioethers [16] to yield alkenyl thioethers in good yield (>76%), whereas thiocyanate anions only add to non-activated alkynes under acidic phase-transfer catalytic conditions on the addition of mercury(II) thiocyanate. Terminal alkynes are converted into vinyl thiocyanates, but disubstituted alkynes also form vinyl isothiocyanates [17]. Major by-products are the ketones formed by solvolysis of the alkynes. 

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