3- propynal, nucleophilic

We won t study the details of this substitution reaction until Chapter 11 but for now can picture it as happening by the pathway shown in Figure 8.6. The nucleophilic acetylide ion uses an electron pair to form a bond to the positively polarized, electrophilic carbon atom of bromomethane. As the new C-C bond forms, Br- departs, taking with it the electron pair from the former C-Br bond and yielding propyne as product. We call such a reaction an alkylation because a new alkyl group has become attached to the starting alkyne. 

Evidence for the occurrence of vinyl cations as short-lived intermediates in solvolysis and other reactions has accumulated in the last few years (reviewed by Hanack, 1970, by Richey and Richey, 1970, and by Modena and Tonellato, 1971), but they have not been observed spectroscopically. It has been shown possible to intercept some vinyl cations—prepared in a system of extremely low nucleophilicity (EHSO3—SbEj 1 1-1 10) by protonation of propyne and 2-butyne— by carbon monoxide (Hogeveen and Roobeek, 1971b). The oxocarbo-nium ions formed in these cases are shown in the following scheme ... 

Treatment of propyne iminium triflate 258 with silylated phosphorus nucleophiles such as Me3SiPPhR affords (3-morpholinoallenyl)phosphanes 259 in high yield (Scheme 8.69) [150]. 

Propyne reacts with strong bases to form a nucleophilic carbanion which displaces Br from Br2 by attacking... 

Some 2-carbonyl-l-propargyl-l//-indoles 159 are prepared by means of Suzuki- and Negishi-type reactions <2006OL4839>. 2-Carbonyl-1/f-indoles 158 were converted into the corresponding A -propargyl derivatives in good to excellent yield by means of PTC nucleophilic substitution in toluene/aqueous NaOH and BuaNBr as the catalyst (Equation 28). l-[l-(2-Propyn-l-yl)-12/-pyrrol-2-yl]ethanone was obtained in 86% yield by similar route. 

Treatment of the imide hydride Cp 2Ta(=NBu )H with [Ph3C][B(C6F5)4] yields the cationic imide [Cp 2Ta-(=NBu )(THF)][B(C6F5)4] (22). (22) reacts cleanly with H2 to yield [Cp 2Ta(NHBu )H][B(C6F5)4], and undergoes C-H bond activation reactions with propyne or pheny-lacetylene to afford [Cp 2Ta(NHBuO(C=CR)][B(C6F5)4] (R = Me, Ph). The heterolytic cleavage reactions of (22) may be the result of the presence of both electrophilic and nucleophilic sites of reactivity in the same molecule. Intramolecular activation of a C-H bond of a Cp lig-I------------------------------1... 

Acetylide ion alkylation is limited to primary alkyl bromides and iodides, RCHgX, for reasons that will be discussed in detail in Chapter 11. In addition to their reactivity as nucleophiles, acetylide ions are sufficiently strong bases that they cause dehydrohalogenation instead of substitution when they react with secondary and tertiary alkyl halides. For example, reaction of bromocyclohexane with propyne anion yields the elimination product cyclohexene rather than the substitution product cyclohexylpropyne. 

Tandem chain extension at both the 1-alkyne and propargylic positions of 1-alkynes by sequential (1) alkylation and (2) hydroxy-alkylation (1,2-addition) of 1,3-dilithiated alkynes provides an attractive, one-pot preparation of functionally disubstituted alkynes. The required 1,3-dilithiated species are obtained by lithiation of 1-alkynes at both the 1- and 3- positions with two equivalents of n-BuLi in the presence of TMEDA (tetramethylethylenediamine). The two-stage chain extension depicted below for propyne involves initial alkylation of the dilithiated propyne with the less reactive electrophile, n-BuBr, at the more nucleophilic propargylic position. Subsequent hydroxyalkylation at the less nucleophilic alkynylide position with the more electrophilic formaldehyde furnishes the a-hydroxyalkyne. ... 

The essential feature of the catalyst systems is that they are formed by the combination of a palladium(II) species with a ligand containing a 2-pyridylphosphine moiety and a proton source containing anions weakly coordinating to palladium [8]. These catalysts are very efficient for the conversion of propyne (for example) as the alkyne and methanol as the nucleophilic co-reagent. 

The above-mentioned low-barrier slipping movement of the propyne molecule on the pathway to MMA minimizes the steric hindrance between propyne s H-atom and (medium-sized) 6-pyridyl substituents on subsequent rotation and nucleophilic attack (which is rate-determining vide infra) by the carbomethoxy group. 

Very similar results to those described with propyne can be obtained with a wide variety of other alkynes, e. g., acetylene, higher aliphatic and aromatic alkynes as well as other nucleophilic reagents, such as water, aliphatic (primary, secondary, and tertiary) and aromatic alcohols, thiols, and amines. 

Bhanu and Scheinmann " have shown that the dilithium salt of propyne alkylates firstly on the methyl group and then on the alkyne. The process occurs sequentially and two different electrophiles can be used. The reaction gave superior yields when the second electrophile underwent nucleophilic addition rather than substitution (Scheme 20). 

Homoenolate and homoallenyl carbanion equivalents. Two routes to homo-cnolate species are based on the action of (propene)titanium diisopropoxide. Trialkoxy-titanates generated from acetals of acrolein react with aldehydes and imines. Chiral cyclic acetals are similarly cleaved to afford the nucleophiles. 3-Alkoxy-2-propyn-l-yl carbonates are transformed into (l-alkoxyallen)-l-yltitanates that add to carbonyl compounds with y-selectivity. ... 

Intramolecular cyclopropanations of pendant alkenes are more favorable. Heteroatom-substituted 2-aza- and 2-oxabicyclo[3.1.0]hexanes, together with 2-oxabicyclo[4.1.0] heptanes, can be prepared from chromium and tungsten Fischer carbenes having a tethered alkene chain. An interesting carbene formation via a cationic alkylidene intermediate, nucleophilic addition see Nucleophilic Addition Rules for Predicting Direction), mA intramolecular cyclopropanation is shown in Scheme 59. An intramolecular cyclopropanation via reaction of alkenyl Fischer carbene complex (28) and propyne was used in a formal synthesis of carabrone (Scheme 60). 

The other major synthetic use of alkyne anions is their reaction with ketones and aldehydes to give an alkynyl alcohol via nucleophilic acyl addition. The lithium salt of 1-propyne, for example, reacted with aldehyde 40 to give alcohol 41 as part of Smith s synthesis of (+)-acutiphycin.50 The reaction is selective for ketones and aldehydes in the presence of acid derivatives, if the acetylide is not present in large excess. l... 

In agreement with the tendency shown by 133 to release a phosphine ligand, the treatment of this compound with 1 equiv of l,l-diphenyl-2-propyn-l-ol in pentane at room temperature leads to the 71-alkynol complex Os(ti5-C5H5)C1 ti2-HCsC(OH)Ph2 (P Pr3) (150). In toluene at room temperature, this compound is stable. However, at 85 °C, it evolves into the allenylidene derivative Os(ti5-C5H5)Cl(C=C=CPh2)(P Pr3) (151), which has a very remarkable nucleophilic character [58]. 

---