Alkyne anions reaction with aldehydes

These compounds are sources of the nucleophilic anion RC=C and their reaction with primary alkyl halides provides an effective synthesis of alkynes (Section 9 6) The nucleophilicity of acetylide anions is also evident m their reactions with aldehydes and ketones which are entirely analogous to those of Grignard and organolithium reagents... 

Alkynes from aldehydes or ketones. The reaction of the anion ef 1 with diaryl ketones, ArCOAr, to form alkynes, ArC=CAr, was reported first by Colvin and Hamill, but the method was said to fail or give low yield with substrates with enolizable hydrogens. Since then experimental details have been perfected, and the method has proved to be useful." The anion of 1 is prepared with potassium f-butoxide, and the reaction with the carbonyl compound is conducted for 12-16 hours at —78° before it is allowed to warm to the ambient temperature. Linder these conditions, alkynes can be obtained in 50-80% yield from aldehydes, diaryl ketones, and alkyl aryl ketones, but not from dialkyl ketones. The proposed mechanism is shown in equation (I). 

The conjugate base of an alkyne is an alkyne anion (older literature refers to them as acetylides), and it is generated by reaction with a strong base and is a carbanion. It funetions as a nucleophile (a source of nucleophilic carbon) in Sn2 reactions with halides and sulfonate esters. Acetylides react with ketones, with aldehydes via nucleophilic acyl addition and with acid derivatives via nucleophilic acyl substitution. Acetylides are, therefore, important carbanion synthons for the creation of new carbon-carbon bonds. Some of the chemistry presented in this section will deal with the synthesis of alkynes and properly belongs in Chapter 2. It is presented here, however, to give some continuity to the discussion of acetylides. 

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... 

KHMDS is a strong enough base to deprotonate terminal alkynes. It has been particularly useful for the intramolecular condensation of alkyne anions with aldehydes. For instance, the final cycliza-tion in the synthesis of a new bicyclic tetrahydropyridine system was carried out in the presence of KHMDS (eq 40). The same reaction failed when using LDA in THE... 

Bis-allyl complexes were shown to undergo sequential nucleophilic allylation-alkoxyallylation reactions with alkynyl aldehydes such as 127 (Scheme 12.60) [141]. First, the in sitM-formed bis-allylpaUadium complex reacts with the aldehyde in a nucleophilic manner. Subsequent attack of the resulting alkoxy anion on the alkyne... 

The real value of this acid-base reaction is to transform a weak acid into an anion by using a powerful base the organolithium reagent. Such anions behave as nucleophiles in various reactions. In Chapter 11 (Section 11.3.6), alkyne anions underwent Sn2 reactions with alkyl halides. In Chapter 18 (Section 18.3.2), alkyne anions react with aldehydes and ketones. Both Grignard reagents and organolithium reagents react as nucleophiles with aldehydes and ketones (also described in Chapter 18, Section 18.4). Lithium amides such as 45 react as bases with aldehydes or ketones in Chapter 22 (Section 22.3). Many such examples are discussed in this book. 

Benzene was introduced in Chapter 5 (Section 5.10). Chapter 21 will discuss many benzene derivatives, along with the chemical reactions that are characteristic of these compounds. In the context of dissolving metal reductions of aldehydes, ketones, and alkynes, however, one reaction of benzene must be introduced. When benzene (65) is treated with sodium metal in a mixture of liquid ammonia and ethanol, the product is 1,4-cyclohexadiene 66. Note that the nonconjugated diene is formed. The reaction follows a similar mechanism to that presented for alkynes. Initial electron transfer from sodium metal to benzene leads to radical anion 67. Resonance delocalization as shown shordd favor the resonance contributor 67B due to charge separation. 

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. 

The reaction of carbon nucleophiles with ketones or aldehydes proceeds by acyl addition, as described in Chapter 18. The reaction of carbon nucleophiles with acid derivatives proceeds by acyl substitution, as described in Chapter 20. Carbon nucleophiles included cyanide, alkyne anions, Grignard reagents, organolithium reagents, and organocuprates. Alkyne anions are formed by an acid-base reaction with terminal alkynes (RC=C-H RCsCr). In this latter transformation, it is clear that formation of the alkyne anion relies on the fact that a terminal alkyne is a weak carbon acid. Other carbon acids specifically involve the proton on an a-carbon in aldehydes, ketones, or esters. With a siiitable base, these carbonyl compounds generate a new type of carbon nucleophile called an enolate anion. 

Reaction with Anions of Terminal Alkynes (Section 16.5C) Treating an aldehyde or a ketone with the alkali metal salt of a terminal alkyne followed by hydrolysis gives an a-aUcynylalcohol. 

A new synthesis of aldehydes with 2-methyl-2-thiazoline has the advantage of releasing the aldehydes from the thiazolidine intermediate under neutral conditions . Acetylene derivatives can be obtained from aldehydes via dibromomethylene compounds Novel reactions of alkynes with cationoid electrophiles have been published. -Diketones and 2-ketoalkoximes can be obtained by this reaction from acid chlorides and aliphatic nitro compounds respectively Addition of aldehydes to activated carbon-carbon double bonds occurs smoothly in the presence of cyanide ions as catalysts . Poly- -carbonyl compounds have been prepared by condensation of two anions, whereby the enolate salt of a y8-keto ester condenses as an electrophilic anion with strong nucleophiles such as the dianion of benzoylacetone. ... 

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