Nucleophilic substitution alkynes

Alkynes of the type RC CH may be prepared by nucleophilic substitution reactions in which one of the starting matenals is sodium acetyhde (Na" C=CH)... 

Anions of acetylene and terminal alkynes are nucleophilic and react with methyl and primary alkyl halides to form carbon-carbon bonds by nucleophilic substitution Some useful applications of this reaction will be discussed m the following section... 

This scheme represents an alkyne-bromine complex as an intermediate in all alkyne brominations. This is analogous to the case of alkenes. The complex may dissociate to a inyl cation when the cation is sufficiently stable, as is the case when there is an aryl substituent. It may collapse to a bridged bromonium ion or undergo reaction with a nucleophile. The latta is the dominant reaction for alkyl-substituted alkynes and leads to stereospecific anti addition. Reactions proceeding through vinyl cations are expected to be nonstereospecific. 

The direct, stereoselective conversion of alkynes to A-sulfonylazetidin-2-imines 16 by the initial reaction of copper(l) acetylides with sulfonyl azides, followed, in situ, by the formal [2+2] cycloaddition of a postulated A-sulfonylketenimine intermediate with a range of imines has been described <06AG(E)3157>. The synthesis of A-alkylated 2-substituted azetidin-3-ones 17 based on a tandem nucleophilic substitution followed by intramolecular Michael reaction of primary amines with alkyl 5-bromo-4-oxopent-2-enoates has been... 

The thiadiazoline (50) (Ar = p-Tol) reacts with electron-deficient alkynes (51) to give arylimino-thiazoles (53). It has been suggested that the reaction proceeds via a 1,3-dipolar cycloadduct (52) (Scheme 13) <75TL459> or by a stepwise nucleophilic substitution reaction <84CHEC-I(6)463>. 

In conjunction with this, Jeong reported the cycloadditions of bis(allyl) and bis(homoallyl) acetals of alkynals leading to bicyclic lactols. Smaltz extended its utility to the synthesis of carbocyclic nucleoside by coupling with nucleophilic substitution of a 7r-allylic palladium complex (Equation (46)). ... 

They react with alkyl halides to give internal alkynes (see Section 5.5.2) via nucleophilic substitution reactions. This type of reaction also is known as alkylation. Any terminal alkyne can be converted to acetylide and alkynide, and then alkylated by the reaction with alkyl halide to produce an internal alkyne. In these reactions, the triple bonds are available for electrophilic additions to a number of other functional groups. 

It is also possible to achieve the formation of five-membered rings by coupling the allylzincation of a metallated alkyne with an intramolecular nucleophilic substitution. Thus, allylzincation of the ethylzinc alkynylide generated from 5-iodo-l-pentyne (66)45, or direct treatment of the latter with excess crotylzinc chloride177, led to the alkenyl... 

Resin-bound amines can be converted into imines [710,711] or enamines by reaction with carbonyl compounds (Entries 6 and 7, Table 3.39). Resin-bound enamines have also been prepared by Michael addition of resin-bound secondary amines to acceptor-substituted alkynes [712], by Hg(II)-catalyzed addition of resin-bound secondary amines to unactivated alkynes [713], by addition of C-nucleophiles to resin-bound imino ethers [714], and by chemical modification of other resin-bound enamines [712,713,715], Acceptor-substituted enamines ( push-pull alkenes) are not always susceptible to hydrolytic cleavage by TFA alone and might require aqueous acids to undergo hydrolysis [716]. 

With those RX derivatives that undergo nucleophilic displacement readily, this is a general method of forming a C—C bond, thereby leading to substituted alkynes. The alkynide salts generally used are those of lithium, sodium, potassium, or magnesium. 

Cyclizations with nitrogen nucleophiles involving alkynes and allenes have received little attention until recently. The cyclizations of several a-aminoallenes to 3-pyrrolines with silver tetrafluoroborate was reported by Claesson and coworkers (equation 133).264 A similar cyclization to form A -carba-penems has been reported (equation 134).265 Diastereomeric allenes (R1 R2) were shown to cyclize with complete stereocontrol. Cyclization with palladium chloride in the presence of allyl bromide or electrophilic alkenes allowed for the intermediate vinylpalladium species to be trapped by the electrophile.2651 A related product was obtained by cyclization of an alkynic substrate (equation 13S).265 Other examples of 5-endo cyclization of p-aminoalkynes50 include the formation of indoles by cyclization of 2-alkynylanilines with mercury salts200 or palladium chloride,266a,266b,266c formation of 1-pyrrolines with catalytic palladium chloride (equation 136)198 and formation of pyrroles by cyclization of hydroxy-substituted p-aminoalkynes.198,2666... 

Reactions of alkynyliodonium salts 119 with nucleophiles proceed via an addition-elimination mechanism involving alkylidenecarbenes 120 as key intermediates. Depending on the structure of the alkynyliodonium salt, specific reaction conditions, and the nucleophile employed, this process can lead to a substituted alkyne 121 due to the carbene rearrangement, or to a cyclic product 122 via intramolecular 1,5-carbene insertion (Scheme 50). Both of these reaction pathways have been widely utilized as a synthetic tool for the formation of new C-C bonds. In addition, the transition metal mediated cross-coupling reactions of alkynyliodonium salts are increasingly used in organic synthesis. 

Alkynyl(phenyl)iodonium salts can be used for the preparation of substituted alkynes by the reaction with carbon nucleophiles. The parent ethynyliodonium tetrafluoroborate 124 reacts with various enolates of /J-dicarbonyl compounds 123 to give the respective alkynylated products 125 in a high yield (Scheme 51) [109]. The anion of nitrocyclohexane can also be ethynylated under these conditions. A similar alkynylation of 2-methyl-1,3-cyclopentanedione by ethynyliodonium salt 124 was applied in the key step of the synthesis of chiral methylene lactones [110]. 

Sn2 mechanism (Scheme 47) [138,139]. Concerted,in-plane nucleophilic substitutions of this type are facilitated by the exceptional nucleofugality of iodoben-zene, and appear to be operative with weakly basic nucleophiles. Similar reactions of ( )-/ phenylvinyl(phenyl)iodonium tetrafluoroborate are slower, less stereoselective, and more prone to competitive alkyne formation. 

Enynes (77) can react with arylboronic acids in the presence of a catalytic amount of a rhodium(I) complex under mild conditions to give (Z)-l-(l-arylethyl- (g) idene)-2-vinylcyclopentanes (78).100 In analogy, the rhodium-catalysed cyclization of the cyano-substituted alkynes (79) with arylboronic acids has been reported to produce the cyclic ketone (80) as the first example of a nucleophilic addition of an Rh(I) species to a cyano group.101... 

Once the alkynide is formed, it can be treated with an alkyl halide to form more complex alkynes. This reaction is called an alkylation and is an example of nucleophilic substitution. 

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