Anions from Alkynes

The amide ions are powerful bases and may be used (i) to dehydrohalogenate halo-compounds to alkenes and alkynes, and (ii) to generate reactive anions from terminal acetylenes, and compounds having reactive a-hydrogens (e.g. carbonyl compounds, nitriles, 2-alkylpyridines, etc.) these anions may then be used in a variety of synthetic procedures, e.g. alkylations, reactions with carbonyl components, etc. A further use of the metal amides in liquid ammonia is the formation of other important bases such as sodium triphenylmethide (from sodamide and triphenylmethane). 

After addition of the alkyne anion to the alkylborane, iodination facilitates alkyl group migration from boron to carbon in a transfer that resembles the one seen in the synthesis of (Z)-alkenes described in Section B4.1. Elimination to give the product alkyne occurs under the iodination reaction conditions (Figure B4.4). 

The first alkyne cyclisations, from 377, 379 and 381, predate the early alkene cyclisations by a couple of years these three date from 1966173 and 1967,174 and illustrate the favourability of both exo and endo-dig cyclisation. All three generate benzylic vinyllithiums (378, 380 and 382), and both aryl (377, 379) and alkyl halides (381) are successful starting materials. Similar organomagnesium cyclisations were described at about the same time.175 However, it is not clear in these reactions how much of the product is due to participation of radicals in the mechanism - alkylbromides undergo halogen-metal exchange with alkyllithiums via radical intermediates (chapter 3).176 If it really is an anionic cyclisation, cyclisation to 378 is remarkable in being endo. Endo-dig anionic cyclisations are discussed below. 

Formation of acetylide anions from terminal alkynes (11 6B)... 

Anions from the stronger carbon acids are accessible and give expected products (see Table 22, p. 897). Invariably, the alkyne carries an activating substituent. Cyclic products form when possible (the additions of the azallyl anions of equation (184)... 

The benzoate ion is the product under the reaction conditions but the alkyne anion collects a oton from a water molecule, regenerating the second hydroxide ion, which therefore is a base... 

Recent evidence for the formation of hemiketal intermediates iqmn acylation of alkynides has been obtained from glucopyranolactones. Treatment of tetrabenzyl (55) with the anion from l-benzyloxy-3-bu-tyne gave a quantitative yield of hemiketal (56) which showed IR absorptions for the OH and alkyne portions of the molecule (X = 3350 cm" and 2250 cnr, respectively). This compound was stereospecifi-cally reduced to the C-glycoside (57) with triethylsilane/BFs-etherate (overall yield 72% Scheme 18). None of the other stereoisomer or ring-opened product was obtained. ... 

As noted above, alkyne anions are very useful in Sn2 reactions with alkyl halides, and in acyl addition reactions to a carbonyl.46 Alkyl halides and sulfonate esters (tosylates and mesylates primarily) serve as electrophilic substrates for acetylides. A simple example is taken from Kaiser s synthesis of niphatoxin B, in which propargyl alcohol (36) is treated with butyllithium and then the OTHP derivative of 8-bromo-1-octanol to give a 47% yield of 37.48... 

The first proton to be removed by base will be from the alcohol and this will need a reasonably strong base such as NaH. Removal of the alkyne proton requires a much stronger base such as BuLi. You might represent the product as an alkyne anion or a covalently bonded alkyllithium. 

Each alkyne can be synthesized by alkylation of an appropriate alkyne anion. First decide which new carbon-carbon bond or bonds must be formed by alkylation and which alkyne anion nucleophile and haloalkane pair is required to give the desired product. Synthesis of a terminal alkyne from acetylene requires only one nucleophilic substitution, and synthesis of an internal alkyne from acetylene requires two nucleophilic substitutions. 

The new functional group exchange reactions presented in this chapter can be combined with reactions from previous chapters to expand the ability to synthesize molecules. Alkene 85 is synthesized from aldehyde 86, for example. The first task is to identify the four carbons of 86 in 85. It appears that the carbons marked in blue are the best candidates. Rather than disconnect the C-C=C unit marked in blue, first disconnect the ethyl group of 85 to give 87 and 88. This choice is made because no reaction has been presented that will allow direct incorporation of EtCHCH to X-C-CMea. Disconnection of the ethyl group takes advantage of the fact that an alkyne anion reacts with an alkyl halide. However, before this reaction can be used, the alkene unit in 87 needs to be changed to an alkyne unit in 89. 

It is clear from this last example that an enolate anion behaves as a carbon nucleophile and gives the same sort of acyl addition reaction as another previously discussed carbanion, an alkyne anion (see Chapter 18, Section 18.3.2). The products are different, of course, but from the standpoint of comparing reactions, the only real difference between an enolate anion and an alkyne anion is the structure and complexity of the enolate anion as a carbon nucleophile and the functionality in the fined acyl addition product. 

Also, as was the case for alkenes, the carbon-carbon triple bond can be reduced by active metals (e.g., sodium, Na, lithium, and Li) in the presence of a proton donor, such as ethanol (ethyl alcohol, CH3CH2OH). Interestingly, the reduction appears to occur in a series of one-electron transfer steps (first to a radical or radical-Uke species and then to an anion) from the active metal to the alkyne in liquid ammonia (NH3(i)) solvent followed by the transfer of the proton. The alkene produced arises from net antarafacial [or tram-, anti-, or ( )-] hydrogen addition ( nation 6.66). 

The yield of product from the carbon dioxide reaction with the alkyne anion was very poor, as it was with the vinyl Grignard derived from 1.166. Extending the carbon chain between the triple bond and the dimethylamino group, as in the reaction of 1.170 with sodium amide and then carbon dioxide, - however, led to... 

High yields of alkynes can be obtained from the reaction of 1,1-dichloromethyl-lithium with alkyl halides and subsequent dehydro-halogenation. The alkyne anion (40) with alkyl halides gives a-substituted prop-2-ynylamines and with CO2 gives a-acetylenic amino-acids, in good yields. 

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