Sodium acetylide generation

The problems of handling liquid ammonia are alleviated in this modification of the sodium acetylide generation procedure. Finely divided sodium is prepared in boiling toluene, the toluene is replaced by THF, and a direct reaction between sodium and acetylene is carried out. The resulting sodium acetylide is employed in ethynylation reactions as before. 

Acetylenes are sufficiently acidic to react with sodium metal to generate acetylides, useful nucleophiles in the formation of carbon-carbon bonds. The reaction is classically carried out in liquid ammonia, which is a good solvent for alkali metals but which is troublesome to handle. Two convenient modifications of the acetylide generation reaction overcome this difficulty and are discussed below along with the classical method. 

The most convenient method for the preparation of sodium acetylide appears to be by reaction of acetylene with sodium methylsulfinyl carbanion (dimsylsodium). The anion is readily generated by treatment of DMSO with sodium hydride, and the direct introduction of acetylene leads to the reagent. As above, the acetylide may then be employed in the ethynylation reaction. 

We see from these examples that many of the carbon nucleophiles we encountered in Chapter 10 are also nucleophiles toward aldehydes and ketones (cf. Reactions 10-104-10-108 and 10-110). As we saw in Chapter 10, the initial products in many of these cases can be converted by relatively simple procedures (hydrolysis, reduction, decarboxylation, etc.) to various other products. In the reaction with terminal acetylenes, sodium acetylides are the most common reagents (when they are used, the reaction is often called the Nef reaction), but lithium, magnesium, and other metallic acetylides have also been used. A particularly convenient reagent is lithium acetylide-ethylenediamine complex, a stable, free-flowing powder that is commercially available. Alternatively, the substrate may be treated with the alkyne itself in the presence of a base, so that the acetylide is generated in situ. This procedure is called the Favorskii reaction, not to be confused with the Favorskii rearrangement (18-7). ... 

Sodium acetylides are the most common reagents, but lithium, magnesium and other metallic acetylides have also been used. A particularly convenient reagent is lithium acetylide-ethylene diamine complex. Alternatively, the substrate may be treated with the alkyne itself in the presence of a base, so that the acetylide is generated in situ. 1,4-Diols can be prepared by treatment of aldehyde with dimetalloacetylenes. 

In the preparation of 1-pentyne and 1-hexyne (exp. 10) complete conversion of the alkyl bromides is effected by using an excess of sodium acetylide. A reasoning based on economics prompts the use of an excess of the alkyl halide if alkali vinylacetylide or alkali diacetylide (generated from alkali amide and dichlorobutene or dichlorobutyne, respectively) are to be alkylated. If slightly mare than the stoichiometiical amount of alkyl bromide is used, no serious separation problems will be encountered during the final distillation. A relatively small amount of DMSO is added to enhance the solubility of the alkyl bromides, thereby facilitating the alkylation reaction. 

Aryl triflates 35, generated from the corresponding phenols, react with lithium diisopropylamide (EDA) in diisopropylamine (DIA) to give 36 in good yield. The reaction was demonstrated (via substitution pattern in the products) to proceed via an aryne intermediate. The choice of LDA as the base is critical BuLi, NaNH2, sodium acetylide and 2-lithiofuran all failed to generate an aryne from 35 (R = p- h). Application of the method to other nucleophiles than DIA, or to cycloadditions, has not yet been demonstrated. 

On the basis of the above-mentioned calculations it seems that coordination chemistry is a viable alternative to stabilize this heterocumulene. However, the experimental access to metal complexes containing the tricarbon monoxide ligand remains a challenge. Thus, to date, the coordination chemistry of C3O is confined to [Cr(=C=C=C=0)(C0)s] (89), obtained by treatment of [n-Bu4N] [CrI(CO)5] with the silver acetylide derived of sodium propiolate in the presence of Ag" (Scheme 28) [105]. Reaction of the presumed Tt-alkyne intermediate complex 88 with thiophosgene generates the heterocumulene 89. Neither structural nor reactivity studies were undertaken with this complex. 

The propargylic alcohol group may be exploited as an allylic alcohol precursor (Eq. 6A.2) and may be generated by nucleophilic addition to an electrophile [25] or by addition of a formaldehyde equivalent to a preexisting terminal acetylene group [26], Once in place, reduction of the propargylic alcohol with lithium aluminum hydride or, preferably, with sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) [27] will produce the trans allylic alcohol. Alternately, catalytic reduction over Lindlar catalyst can be used to obtain the cis allylic alcohol [28]. The addition of other lithium acetylides to ketones produces chiral secondary alcohols, which also can be reduced by the preceding methods to the cis or trans allylic alcohols. Additional synthetic approaches to allylic alcohols may be found in the various references cited in this chapter. 

Acetylide anion (Section 10.8) A carbon nucleophile generated by treating 1-alkynes with a very strong base, such as sodium amide RC=C . 

The alkyl azide is generated in situ from the corresponding alkyl halides and sodium azide, whereupon it is captured by copper(I) acetylide forming the desired triazole 45. The reaction is performed under the action of MW irradiation for 10 min at 125 °C. Although most compounds readily tolerated this temperature, occasionally it resulted in reduced yields. To circumvent these problems these reaction mixtures were irradiated for 15 min at 75 °C. The reaction was performed in a 1 1 mixture of t-BuOH and water and the Cu(I) catalyst was prepared in situ by... 

An interesting solution to the problem described above was put forth by Olah and others. In situ generation of methoxy acetylide precludes the use of methoxyacetylene, and provides for the efficient one-pot conversion of 34 to 36. The acetylide anion can be efficiently generated under a variety of conditions,including sodium in ammonia or LDA in THF. ... 

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