Synthesis Using Acetylide Ions

Route (b), using acetylIde ion, has been used for the synthesis of (26) which did Indeed give the right dlastereoisomer of (23) with maleic anhydride. Synthesis... 

Solvent for Displacement Reactions. As the most polar of the common aprotic solvents, DMSO is a favored solvent for displacement reactions because of its high dielectric constant and because anions are less solvated in it (87). Rates for these reactions are sometimes a thousand times faster in DMSO than in alcohols. Suitable nucleophiles include acetylide ion, alkoxide ion, hydroxide ion, azide ion, carbanions, carboxylate ions, cyanide ion, halide ions, mercaptide ions, phenoxide ions, nitrite ions, and thiocyanate ions (31). Rates of displacement by amides or amines are also greater in DMSO than in alcohol or aqueous solutions. Dimethyl sulfoxide is used as the reaction solvent in the manufacture of high performance, polyaryl ether polymers by reaction of bis(4,4,-chlorophenyl) sulfone with the disodium salts of dihydroxyphenols, eg, bisphenol A or 4,4,-sulfonylbisphenol (88). These and related reactions are made more economical by efficient recycling of DMSO (89). Nucleophilic displacement of activated aromatic nitro groups with aryloxy anion in DMSO is a versatile and useful reaction for the synthesis of aromatic ethers and polyethers (90). 

In these alkylation reactions primary alkyl halides (the bromide for preference) should be used as the alkylating agents, since secondary and tertiary halides undergo extensive olefin-forming elimination reactions in the presence of the strongly basic acetylide ion. A typical synthesis is that of hex-l-yne (Expt 5.26). 

Bauerle and coworkers have adapted the Cu+ template (48) approach to [2]cate-nane synthesis using an intermediate platinum diacetylide linkage to macrocyclize each of the two rings (49, Scheme 10.9) [38], Oxidation of the platinum centers in the macrocyclic rings of SO with I2 induces reductive elimination of the two acetylides to form the 1,3-butadiyne linked macrocycles (51). Unfortunately, the authors could not remove the copper template in this example, likely as a result of steric congestion about the metal ion in the interlocked product. 

Using retrosynthetic analysis, we recognize that the c/.v-epoxide can be prepared from the c/s-alkene. The m-alkene can be prepared by catalytic hydrogenation of an alkyne. Finally, substituted alkynes can be prepared by nucleophilic substitution reactions using acetylide ion nucleophiles (see Section 10.8). On the basis of this analysis, the synthesis reported in the literature was accomplished as shown in Figure 23.3. 

Two different approaches are commonly used for the synthesis of alkynes. In the first, an appropriate electrophile undergoes nucleophilic attack by an acetylide ion. The electrophile may be an unhindered primary alkyl halide (undergoes Sn2), or it may be a carbonyl compound (undergoes addition to give an alcohol). Either reaction joins two fragments and gives a product with a lengthened carbon skeleton. This approach is used in many laboratory syntheses of alkynes. 

The addition of an acetylide ion to a carbonyl group is used in the synthesis of ethchlorvynol, a drug used to cause drowsiness and induce sleep. Ethchlorvynol is relatively nonpolar, enhancing its distribution into the fatty tissue of the central nervous system. 

Specific enol equivalents (e. g. (3-keto esters) and umpolung (e. g., with cyanide or acetylide ions as acyl anion equivalents) have of course been used in synthesis for many years. What is new is the recognition of their role, as a result of the disconnec-... 

The usual a.d-disconnection on (47) is not very productive as it suggests a 1,7-dicarbonyl precursor (49), but the strategically preferable ring-chain disconnection is good providing we have a reagent for acyl anion (SO). We have already met the synthesis of (47) using acetylide ion as the acyl anion equivalent (Chapter 16). 

The anion obtained when the acetylenic hydrogen is removed is known as an alkynide ion or an acetylide ion. As we shall see in Section 7.11, these ions are useful in synthesis ... 

The acetylide ion attacks the epoxide, opening up the strained, three-membered ring and creating an alkoxide ion. After the reaction is complete, a proton source is used to protonate the alkoxide ion. In a synthesis, these two steps must be shown separately, because the acetylide ion will not survive in the presence of HsO. Using this information, propose a plausible synthesis for the following compound using acetylene as your only source of carbon atoms ... 

Figure 7.94 adds several reactions to the ones we have discussed specifically. For example, it sneaks in a brand-new synthesis of substituted alkynes by using the acetylide ion as a nucleophile (usually effective only with primary R—L compounds). We mentioned the acidity of acetylenes in Chapter 3 (p. 129) and even... 

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