Carbanions acetylide

It looks as though all that is needed is to prepare the acetylenic anion, then alkylate it with methyl iodide (Section 9.6). There is a complication, however. The carbonyl group in the starting alkyne will neither tolerate the strongly basic conditions required for anion fonnation nor survive in a solution containing carbanions. Acetylide ions add to carbonyl... 

Total synthesis is applied for carotenoids on a lO t scale per year. One usually starts with the cheapest carbonyl components (formaldehyde, acetone) and carbanions (acetylide, acetoacetate, cyanide, Wittig ylides) available. A typical industrial synthesis of retinol acetate (vitamin A) is outlined in Scheme 5.3,1. 

Certain functional groups may be protected from reduction by conversion to anions that resist reduction. Such anions include the alkoxides of allylic and benzylic alcohols, phenoxide ions, mercaptide ions, acetylide ions, ketone carbanions, and carboxylate ions. Except for the carboxylate, phenoxide, and mercaptide ions, these anions are sufficiently basic to be proton-ated by an alcohol, so they are useful for protective purposes only in the... 

Carbanion (Section 9.5) Anion in which the negative charge is home by carbon. An example is acetylide ion. 

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. 

Methylsulfinyl carbanion (dimsyl ion) is prepared from 0.10 mole of sodium hydride in 50 ml of dimethyl sulfoxide under a nitrogen atmosphere as described in Chapter 10, Section III. The solution is diluted by the addition of 50 ml of dry THF and a small amount (1-10 mg) of triphenylmethane is added to act as an indicator. (The red color produced by triphenylmethyl carbanion is discharged when the dimsylsodium is consumed.) Acetylene (purified as described in Chapter 14, Section I) is introduced into the system with stirring through a gas inlet tube until the formation of sodium acetylide is complete, as indicated by disappearance of the red color. The gas inlet tube is replaced by a dropping funnel and a solution of 0.10 mole of the substrate in 20 ml of dry THF is added with stirring at room temperature over a period of about 1 hour. In the case of ethynylation of carbonyl compounds (given below), the solution is then cautiously treated with 6 g (0.11 mole) of ammonium chloride. The reaction mixture is then diluted with 500 ml of water, and the aqueous solution is extracted three times with 150-ml portions of ether. The ether solution is dried (sodium sulfate), the ether is removed (rotary evaporator), and the residue is fractionally distilled under reduced pressure to yield the ethynyl alcohol. 

Potassium or lithium derivatives of ethyl acetate, dimethyl acetamide, acetonitrile, acetophenone, pinacolone and (trimethylsilyl)acetylene are known to undergo conjugate addition to 3-(t-butyldimethylsiloxy)-1 -cyclohexenyl t-butyl sulfone 328. The resulting a-sulfonyl carbanions 329 can be trapped stereospecifically by electrophiles such as water and methyl iodide417. When the nucleophile was an sp3-hybridized primary anion (Nu = CH2Y), the resulting product was mainly 330, while in the reaction with (trimethylsilyl)acetylide anion the main product was 331. 

Other carbanionic groups, such as acetylide ions, and ions derived from a-methylpyridines have also been used as nucleophiles. A particularly useful nucleophile is the methylsulfinyl carbanion (CH3SOCHJ), the conjugate base of DMSO, since the P-keto sulfoxide produced can easily be reduced to a methyl ketone (p. 549). The methylsulfonyl carbanion (CH3SO2CH2 ), the conjugate base of dimethyl sulfone, behaves similarly, and the product can be similarly reduced. Certain carboxylic esters, acyl halides, and DMF acylate 1,3-dithianes (see 10-10. )2008 Qxj(jatjye hydrolysis with NBS or NCS, a-keto aldehydes or a-... 

It occurs with the alkyls, aryls or acetylides of metals more electropositive than magnesium, but including Grignard reagents, and is often carried out by adding a solution of the organometallic compound in an inert solvent to a large excess of powdered, solid C02 it is a particularly useful method for the preparation of acetylenic acids. The Kolbe-Schmidt reaction (p. 291) is another example of carbanion carbonation. 

Here too, a second alkylation can be made to take place yielding RC=CR or R C=CR. It should, however, be remembered that the above carbanions—particularly the acetylide anion (57)—are the anions of very weak acids, and are thus themselves strong bases, as well as powerful nucleophiles. They can thus induce elimination (p. 260) as well as displacement, and reaction with tertiary halides is often found to result in alkene formation to the exclusion of alkylation. 

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). 

Carbanions in the form of phenylUthium, sodium naphthalene complex, sodium acetylide, or aromatic Grignard reagents react with alkyl sulfates to give a C-alkyl product (30—33). Grignard reagents require two moles of dimethyl sulfate for complete reaction. 

You have already had considerable experience with carbanionic compounds and their applications in synthetic organic chemistry. The first was acetylide ion in Chapter 9, followed in Chapter 14 by organometallic compounds—Grignard reagents, for example—that act as sources of negatively polarized carbon. In Chapter 18 you learned that enolate ions—reactive intermediates generated from aldehydes and ketones—are nucleophilic, and that this property can be used to advantage as a method for carbon-carbon bond formation. 

We can consider decarboxylation reactions in terms that are analogous to those in proton transfer reactions the reactivity of the carbanion in carboxylation reactions is analogous to internal return observed in proton transfer reactions from Bronsted acids. Kresge61 estimated that the rate constant for protonation of the acetylide anion, a localized carbanion (P A 21), is the same as the diffusional limit (1010 M s1). However, achieving this rate is highly dependent on the extent of localization of the carbanion. Jordan62 has shown that intermediates in thiazolium derivatives are also likely to be localized carbanions, which implies that protonation of these intermediates could occur at rates approaching those of other localized carbanions. 

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