Nucleophilic acetylenic substitutions

Isolation of high yields of (201) from the analogous reaction of N-(2-chloroallyl)alkylamine argues against its involvement as a substitution intermediate. The sensitivity of the acetylene to nucleophilic addition rather than its mere isolation should be considered as part of the evidence concerning its role as an essential intermediate. Since neither (199) nor (200) exchange their CH2-hydrogens with the solvent, the isolation of labelled (200) from the reaction in tritiated liquid ammonia excluded (1) as the main substitution, while (2) and (4) are excluded since the exocyclic methylene was not labelled. The incorporation of tritium at... 

In this mode, an umpolung of reactivity for the nucleophile occurs, leading to many useful transformations. More complex pathways are not unusual these include addition to multiple bonds, vinylic and acetylenic substitution, rearrangements - some involving ring-expansion or ring-contraction - generation of reactive intermediates, etc. Solvent effects, especially solvent participation, may add new dimensions to reactivity. 

Ynamines from other Heterosubstituted Acetylenes via Nucleophilic Substitutions... 

Since acetylenic esters of any type, but especially ones with a good leaving group, like sulfonates, were unknown until recently [4], early substrates for nucleophilic acetylenic substitutions [Sn-A] were primarily the haloacetylenes 1 [2, 3, 5]. Unfortunately, product yields in these reactions tend to be moderate at best, usually because of competing reactions including displacement of RC C via direct attack on the halogen itself. 

Using Acetylenic Reactivity Nucleophilic Substitution with Metal Acetylides and Related Reactions... 

Formalistically, reactions 63 and 64 are nucleophilic acetylenic substitutions (Sa -A) with the corresponding anions (sulfonate, phosphate or carboxylate) acting as nucleophiles and alkynyliodonium species 97-99 as the electrophilic substrates. However, the actual details of the mechanism are considerably more complex (equation 66). 

The great majority of known2 reactions of acetylenes are with electrophiles either via the acetylide ions RC=C", or by way of electrophilic addition reactions to the triple bond. Nucleophilic acetylenic substitutions (Sat-A) are generally unfavorable2. Alkynyl(phenyl)iodonium species may serve as synthons for the electrophilic alkynyl... 

Terminal alkyne anions are popular reagents for the acyl anion synthons (RCHjCO"). If this nucleophile is added to aldehydes or ketones, the triple bond remains. This can be con verted to an alkynemercury(II) complex with mercuric salts and is hydrated with water or acids to form ketones (M.M.T. Khan, 1974). The more substituted carbon atom of the al-kynes is converted preferentially into a carbonyl group. Highly substituted a-hydroxyketones are available by this method (J.A. Katzenellenbogen, 1973). Acetylene itself can react with two molecules of an aldehyde or a ketone (V. jager, 1977). Hydration then leads to 1,4-dihydroxy-2-butanones. The 1,4-diols tend to condense to tetrahydrofuran derivatives in the presence of acids. 

In stereoselective antitheses of chiral open-chain molecules transformations into cyclic precursors should be tried. The erythro-configurated acetylenic alcohol given below, for example, is disconnected into an acetylene monoanion and a symmetrical oxirane (M. A. Adams, 1979). Since nucleophilic substitution occurs with inversion of configuration this oxirane must be trens-conilgurated its precursor is commercially available trans-2-butene. 

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... 

Thus, ynaminoketones with 1,2-diaminobenzene form benzodiazepines with retention of the dialkylamino group. The reaction occurs as a nucleophilic addition in the absence of catalysts. With Q, /3-acetylenic ketones 1,2-diaminobenzene reacts in the same manner, but under proton-catalyzed conditions (72LA24). At the same time, ynamines and enynamines furnish with 1,2-diaminobenzene substituted benzimidazoles as aresultof double attack at the acetylene bond(83ZOR926 84ZOR1648). 

Nucleophilic substitution of the nitro group in 3-amino 4-nitrofurazan 185 under conditions of phase-transfer catalysis gave a series of acetylene and diacetylene derivatives (Scheme 43) <2001RJ01629>. 

Simple reaction occurs with aryl halides only when the ring is sufficiently substituted with electron-withdrawing functions to allow attack by the nucleophilic phosphorus.53-56 Generally, reaction with aryl halides requires the presence of a Lewis acid catalyst or some other means of reaction initiation. These reactions will be considered in detail in Chapter 6 of this work. Interestingly, while reactions involving vinylic halides seem to correlate with those of aromatic halides (see Chapter 6), acetylenic halides undergo facile reaction with these phosphorus reagents.57 58... 

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