Reactions with Electrophilic Acetylenes

SCHEME 2.42 Side products formed from benzoylphenylacetylene during its reaction with pyrroles in the KOH/DMSO system. 

SCHEME 2.43 C-Vinylation of 4,5,6,7-tetrahydroindole with benzoylacetylene in the KOH/DMSO system. 

ESR study of the mechanism of pyrrole addition to acyl- and cyanophenylacet-ylenes in the superbase system KOH/DMSO evidences the formation of radicals [502]. One of the signals has been assigned to N-adducts of pyrrolyl radicals with 

The reaction proceeds under mild conditions (room temperature) in the absence of a solvent as well as in protic (methanol, ethanol) and aprotic (ether, benzene, hexane, acetonitrile) solvents to furnish predonunantly Z-isomers of 2-(2-acylvinyl) pyrroles in 52%-87% yields. However, the Z-isomer is readily converted into the ii-isomer in the course of isolation and purification or even upon storage in a solvent. 

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Addition of nitroalkanes 402 (R = Me, Bu, Ph etc.) to methyl acrylate without a solvent in the presence of Amberlyst-21 gives good yields of the esters 403436. An analogous reaction with electrophilic acetylenes, e.g. dimethyl acetylenedicarboxylate, in the presence of potassium fluoride and tetrabutylammonium chloride yields adducts 404 as mixtures of geometrical isomers437. 

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... 

Electron-rich heterocyclic systems such as indolizines react readily with DEAZD (and PTAD) to give substitution products (Eq. 16).141 None of the formal [8 + 2] cycloaddition products (e.g., 89) are observed. This is in direct contrast to the reaction of indolizines with electrophilic acetylenes which gives high yields of cycloaddition products, presumably via a stepwise mechanism, in the presence of palladium on charcoal.142 This example of... 

Different modes of reaction are known for the reaction of 1,1-enediamines with electrophilic acetylenes. Simple 1,1-enediamines undergo cycloaddition reaction which will be discussed in Section V.A119, whereas conjugated 1,1-enediamines act as nucleophiles towards activated acetylenes. 

The regiochemistry of the hydrozirconation of acetylenic selenides with the Schwartz reagent [Cp2Zr(H)Cl] is dependent on the nature of the substituents. For simple acetylenic selenides (R = Ar, n-Bu), ( j-j9-zirconated vinyl selenides were formed exclusively. The reaction with electrophilic reagents has allowed the stereoselective synthesis of ( j-2-halovinylaryl selenides [75], (Ej-2-aryl-vinyl aryl selenides [76], ( , j-l-arylselanylbutadienes [77] and ( j-2-butyltel-luranylvinyl selenides [78] (Scheme 55). 

Acetylene, as is well known, is acidic enough to form acetylide salts with strong bases. A monoacetylide, HCsC M (M = metal), in reactions with electrophiles ( E ) yields a monosubstituted derivative of acetylene, HC=CE. The latter can undergo the same sequence of reactions to produce compounds of the type E C = CE. Consequently, acetylene can be regarded as a reagent equivalent to the synthons HC=C or C = C . If one further considers the possibilities for the transformation of the acetylenic fragment (for example, hydrogenation to the alkene or alkane, hydration to yield ketones, and other... 

The most utilized method for alkylation of alkynes is via alkynylide anions. Their reaction with electrophilic reagents provides access to both terminal and internal alkynes as well as to functionally substituted alkynes. The higher electronegativity of carbon in the sp-hybridization state imparts relatively greater acidity to acetylene and 1-alkynes (pATa 24-26), so that bases such as alkyllithiums, lithium dialkylamides. 

One of the most versatile methods for the synthesis of derivatives with the acetylene or cumulene system consists In deprotonatlon of the starting acetylene or cumulene and subsequent reaction of the anionic or organometal1ic intermediate with an electrophilic reagent. 

Reactions of alkynes with electrophiles are generally similar to those of alkenes. Because the HOMO of alkynes (acetylenes) is also of n type, it is not surprising that there IS a good deal of similarity between alkenes and alkynes in their reactivity toward electrophilic reagents. The fundamental questions about additions to alkynes include the following. How reactive are alkynes in comparison with alkenes What is the stereochemistry of additions to alkynes And what is the regiochemistry of additions to alkynes The important role of halonium ions and mercurinium ions in addition reactions of alkenes raises the question of whether similar species can be involved with alkynes, where the ring would have to include a double bond ... 

Terminal alkynes with no electron-withdrawing group next to the acetylenic linkage when treated with enamines merely add across the double bonds of the enamines (9i). But electrophilic alkynes (those with an electron-withdrawing group next to the acetylenic linkage) undergo cycloaddition reactions with enamines. 

Potassium or lithium derivatives of ethyl acetate, dimethyl acetamide, acetonitrile, acetophenone, pinacolone and (trimethylsilyl)acetylene are known to undergo conjugate addition to 3-(t-butyldimethylsiloxy)-1 -cyclohexenyl t-butyl sulfone 328. The resulting a-sulfonyl carbanions 329 can be trapped stereospecifically by electrophiles such as water and methyl iodide417. When the nucleophile was an sp3-hybridized primary anion (Nu = CH2Y), the resulting product was mainly 330, while in the reaction with (trimethylsilyl)acetylide anion the main product was 331. 

Reactions of salts of 1,2,3-triazole with electrophiles provide an easy access to 1,2,3-triazol-jV-yl derivatives although, usually mixtures of N-l and N-2 substituted triazoles are obtained that have to be separated (see Section 5.01.5). Another simple method for synthesis of such derivatives is addition of 1,2,3-triazole to carbon-carbon multiple bonds (Section 5.01.5). N-l Substituted 1,2,3-triazoles can be selectively prepared by 1,3-dipolar cycloaddition of acetylene or (trimethylsilyl)acetylene to alkyl or aryl azides (Section 5.01.9). 

The reactions of electrophilic alkynes, such as DMAD (dimethyl acetylene-dicarboxylate), with metal per- and poly-chalcogenido complexes have been exploited for the synthesis of homoleptic and heteroleptic 1,2-dithiolene,... 

Besides the above electrophiles, the acetylene—titanium complexes react regioselectively with other acetylenes providing the corresponding titanacyclopentadienes. An example of a homo-coupling reaction is shown in Eq. 9.11 [30], which also displays some synthetic applications [30,31]. Especially noteworthy is the highly regioselective cross-coupling reaction of unsymmetrical internal and terminal acetylenes, which is illustrated in Eq. 9.12... 

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