Acetylenes nucleophilic attack

The direction of primary intermolecular nucleophilic attack at heterosubstituted acetylenes of type HC —X, where X = R2N, RO, RS, is governed by the nature of heteroatom and can be different. 

In certain cases, Michael reactions can take place under acidic conditions. Michael-type addition of radicals to conjugated carbonyl compounds is also known.Radical addition can be catalyzed by Yb(OTf)3, but radicals add under standard conditions as well, even intramolecularly. Electrochemical-initiated Michael additions are known, and aryl halides add in the presence of NiBr2. Michael reactions are sometimes applied to substrates of the type C=C—Z, where the co-products are conjugated systems of the type C=C—Indeed, because of the greater susceptibility of triple bonds to nucleophilic attack, it is even possible for nonactivated alkynes (e.g., acetylene), to be substrates in this... 

The reaction proceeds with isolated double bonds and electron-rich alkynes. Electron-withdrawing groups in the acetylene moiety decelerated the reaction. A plausible mechanism implies the activation of the olefin by coordination of the metal triflate followed by nucleophilic attack of the acetylene or acetylide (Scheme 31). 

The nitrogen atoms in ADC compounds are highly electrophilic. Nucleophilic attack on nitrogen is easy, and as with electrophilic acetylenes, such as dimethyl acetylenedicarboxylate, it seems likely that some cycloaddition reactions of ADC compounds with unsymmetrical substrates proceed via a stepwise mechanism. PTAD is a powerful electrophile, although TCNE is more reactive, and chlorosulfonyl isocyanate is more reactive still.58... 

A nucleophilic attack on the acetylenic ketone functionality of golfomycin A (184) was proposed as a potential pathway to form the benzannulated enyne-allene 185 (Scheme 20.38) [71]. Subsequent biradical formation has been postulated as a possible mechanism to account for its DNA-cleaving properties and antitumor activity. 

Acetaldehyde is the product of the Wacker process. At the end of the fifties oxidation of ethene to ethanal replaced the addition of water to acetylene, because the acetylene/coal-based chemistry became obsolete, and the ethene/petrochemistry entered the commercial organic chemicals scene. The acetylene route involved one of the oldest organometallics-mediated catalytic routes started up in the 1920s the catalyst system comprised mercury in sulfuric acid. Coordination of acetylene to mercury(II) activates it toward nucleophilic attack of water, but the reaction is slow and large reactor volumes of this toxic catalyst were needed. An equally slow related catalytic process, the zinc catalysed addition of carboxylic acids to acetylene, is still in use in paint manufacture. 

Indeed, because of the greater susceptibility of triple bonds to nucleophilic attack, it is even possible for nonactivated alkynes, e.g., acetylene, to be substrates in this reaction.458... 

A shift from allenes to acetylenic products formed from acetylenic alcohols in which trifluoro-methyl groups are replaced by difluoromethyl groups can be explained in terms of lowering the positive character of the terminal acetylenic carbon atom, thus retarding the nucleophilic attack of fluorine at this position.56... 

Scheme 43 shows the details of the different steps involved in the equilibrium. The nucleophilic attack of the P(III) derivative on the acetylenic bond yields a 1,3-dipole which, after a fast protonation, frees aZ ion. If the subsequent addition of this ion occurs on the P atom (reaction a), a P(V) phosphorane is formed, but the addition of Z on the ethylenic C atom (reaction b) results in the formation of an ylide. Both of these reactions occur under kinetic control and, in both cases, X is always an OR group from the initial acetylene dicarboxylic ester. When the acetylenic compound is a diketone and X is an alkyl or aryl moiety, the C=0 group is much more electrophilic and the attack by the Z ion produces an alcoholate (reaction c), a new intermediate which can cyclize on to the P+ to form a phosphorane, or attack the a-C atom to form an ylide as in Scheme 42. Hence, reactions a and c can coexist, and are strongly dependent on the nature of the trapping reagent and of the P compound, but reaction b is blocked, whatever the reagent. This is well illustrated by the reaction of the 2-methoxytetramethylphospholane 147 on diben-zoylacetylene in the presence of methanol as trapping reagent. The proportions of the vinylphosphorane 157 and spirophosphorane 158 formed (Figure 24) are 13% and 84%, respectively.

Coordination of the metal ion activates the carbon-carbon triple bond toward nucleophilic attack to yield a cr-vinyl complex (22), which is a characteristic pathway of metal-catalyzed additions to the acetylenic bond. Protolysis of 22 gives the end product. 

Other products commonly isolated from reactions of DMAD with heterocycles include dimethyl fumarate (17), the acetylene presumably acting as a dehydrogenating agent, and dimethyl methoxyfumarate (18).22 The latter could arise from the addition of methanol, present as an impurity, to the acetylene, or by nucleophilic attack on the carbonyl group of the acetylenic ester followed by expulsion of methoxide ion, which then undergoes a normal nucleophilic addition to the activated triple bond. It can be obtained, among other products, from the reaction of pyridine with DMAD in methanol.23... 

When the electron density of a carbon-carbon bond is reduced by strongly electron-withdrawing substituents, nucleophilic attack at one of the vinylic or acetylenic carbons may occur. Electron withdrawal may be either by induction or by resonance. Examples of nucleophilic addition are shown in Equations 7.49-7.53. 

This reduces the energy of low-lying vacant molecular orbitals of free acetylene in this complex, as compared with analogous orbitals of free acetylene, and consequently the triple bond becomes more accessible to nucleophilic attack. As for nucleophiles, they become supernucleophiles in superbase media because of a sharp increase in their energy (76G817 77AP0133). 

Nonempirical quantum-chemical calculations of acetylide molecules support the ready displacement of alkali metal cations to the bridge position (87IZV2777 88IZV1335, 88IZV1339). This naturally leads to the conclusion that the polarization and deformation of the ir-electronic shell of acetylene must depend on the atomic number of the cation attached to the acetylene anion. However, the acetylene activation in the reaction with ketoximes via acetylides suggests nucleophile attack at a carbanionlike complex, which is of course a week point of the hypothesis. Nevertheless, the electrophilic assistance from the alkali metal cation (Na+) to the... 

In the light of all the data collected, the following heterocyclization mechanisms may be considered (Scheme 84) (i) [3,3]-sigmatropic shift in an intermediate O-vinyloxime (ii) nucleophilic attack on acetylene by... 

First, 7 is converted into its dianion 23 by two equivalents of n-butyllithium. Not only the terminal hydrogen of alkyne 7 but also the propargylic one is acidic. 23 then undergoes intramolecular nucleophilic attack of the terminal chlorine. NH4C1 work-up yields the desired cyclopropyl acetylene 25.8... 

Nucleophilic attack of phosphines on 1,2,3-selenadiazoles leads to formation of selenophosphoranes and substituted acetylenes <2004CHE503>. Thus, 4-phenyl-1,2,3-selenadiazole 54 reacted with tributylphosphine in benzene at room temperature (Scheme 12). In the first stage, the Se-N bond is broken as a result of nucleophilic attack by tributylphosphine. Elimination of a molecule of nitrogen follows. A molecule of phenylacetylene is released from the intermediate and tributylselenophosporane 167 is produced. When triphenylphosphine is used, triphenylselenophos-phorane 168 is formed in quantitative yield after boiling for 1 h. In the reaction of 5-ethoxycarbonyM-mcthyl-1,2,3-selenadiazole 166 with phosphines, selenophosphoranes 167 and 168 are formed in 100% yield. Ethyl but-2-ynecarboxylate 169 was isolated from the reaction mixtures in 92% yield. 

Addition to Acetylenes. Since triple bonds are more susceptible to nucleophilic attack than double bonds, it might be expected that bases would catalyze additions particularly well. This is the case, and vinyl ethers as well as acetals may be produced by the reaction of acetylenes with alcohols (15,15A) (Reaction X). 

Yates and Wright, 1967). Bimolecular nucleophilic attack on an acetylene (Miller, 1956) (158) or radical attack on an alkene (Readio and Skell, 1966) (159) are illustrative of both stepwise processes and overall stereoselectivity. 

For the corresponding cyclization of acetylenic amides 418, Nagasaka etal.347,347a used a mixture of silver(i) triflate and lithium hexamethyldisilazide as the precatalyst. The process is probably initiated by the coordination of AgN(SiMe3)2 (generated in situ from AgOTf and LHMDS) to the triple bond, followed by nucleophilic attack of the lithium amide at the activated alkyne which affords (ZVy-alkylidene-y-butyrolactams 419 in high yields (Scheme 122). 

Arenetellurolates have been used as starting materials for the preparation of heterocyclic compounds. Intramolecular nucleophilic attack by tellurium on the acetylenic carbon in 2-ethynyl-2-propenetellurolate yielded a 2,3-dihydrotellurophene derivative3 (p. 408). 

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