Ketones alkyne anion reacting with

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. 

Alkyne Anion Reacting with a Ketone (Section ie.5C)... 

Alkyne anions react with the carbonyl groups of aldehydes and ketones to form alkynyl alcohols, as illustrated by the following sequence. 

Terminal alkyne anions are popular reagents for the acyl anion synthons (RCHjCO"). If this nucleophile is added to aldehydes or ketones, the triple bond remains. This can be con verted to an alkynemercury(II) complex with mercuric salts and is hydrated with water or acids to form ketones (M.M.T. Khan, 1974). The more substituted carbon atom of the al-kynes is converted preferentially into a carbonyl group. Highly substituted a-hydroxyketones are available by this method (J.A. Katzenellenbogen, 1973). Acetylene itself can react with two molecules of an aldehyde or a ketone (V. jager, 1977). Hydration then leads to 1,4-dihydroxy-2-butanones. The 1,4-diols tend to condense to tetrahydrofuran derivatives in the presence of acids. 

Thiols react directly with non-activated alkynes [15] and with 1-alkynyl thioethers [16] to yield alkenyl thioethers in good yield (>76%), whereas thiocyanate anions only add to non-activated alkynes under acidic phase-transfer catalytic conditions on the addition of mercury(II) thiocyanate. Terminal alkynes are converted into vinyl thiocyanates, but disubstituted alkynes also form vinyl isothiocyanates [17]. Major by-products are the ketones formed by solvolysis of the alkynes. 

Although the acylcobalt tetracarbonyls react with hydroxide ion under phase-transfer conditions, in the presence of alkenes and alkynes they form o-adducts rapidly via an initial interaction with the ir-electron system. Subsequent extrusion of the organometallic group as the cobalt tetracarbonyl anion leads to a,(J-unsaturated ketones (see Section 8.4). In contrast, the cobalt carbonyl catalysed reaction of phenylethyne in the presence of iodomethane forms the hydroxybut-2-enolide (5) in... 

OxazoIones are alkylated at position 4 by alkyl halides, allyl halides and electrophilic alkynes, such as methyl propiolate (equation 36). In contrast, 2-phenyloxazolones react with methyl vinyl ketone at both C(4) and C(2) to yield a mixture of Michael adducts (equation 37). If the phenyl substituent is replaced by the bulky 2,4,6-trimethylphenyl group the addition is directed exclusively to C(4) (81CB2580). Alkylation of 5(4//)-oxazolones is a key step in the synthesis of ketones from a-amino acids (Scheme 16). The outcome of this sequence is the union of the electrophilic fragment R3 with the group R2CO the amino acid thus functions as the equivalent of an acyl anion (78AG(E)450). 

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... 

If the carbon atom in 3 is electrophilic, then the carbon in 2 must be nucleophilic. This assumption is based on simple bond polarization and it makes it possible to correlate the imaginary 3 with a carbonyl compound that has an electrophilic carbon with a polarized C-0 bond. Nucleophilic acyl addition to a ketone is a known reaction, so 3 correlates with a real molecule—acetone. If 3 correlates with an electrophilic center, then 2 must be a nucleophilic center and an alkyne anion is a reasonable choice. It is known that an alkyne anion will react with a ketone via acyl addition (see Chapter 18, Section 18.3.2). The correlation of 2 with an alkyne simply requires adding a hydrogen atom to the red carbon to give terminal alkyne, 7. Conversion of alkyne 7 to the anion, followed by acyl addition to acetone, should lead to 1. Disconnection of 1 generates acetone and 7, and the reaction of 7 and acetone leads to 1. Recognizing the forward and reverse relationships is essential for correlating the disconnection (retrosynthesis) with the reactions that make the bond (synthesis). 

Other organometallics also react with ketones and imines. For example, the alkyne anions that we prepared in Chapter 8 (remember that the p/[Pg.644]

Reaction of carbanions with dialkynic ketones, the so-called skipped diynes, can produce pyranones through an initial Michael condensation. It should be noted however that diynones are vulnerable to attack at several sites and that mixed products can be formed. Addition of the anions derived from diethyl malonate and ethyl cyanoacetate to hepta-2,5-diyn-4-one (313 R1 = Me) gives the pyranones (314 R2 = C02Et or CN Scheme 91) (74JOC843). The former carbanion reacts similarly with the diynone (313 R1 = Bun) (68T4285). The second alkyne moiety appears to have little effect on the course of the reaction, which parallels the synthesis of pyranones from monoalkynic ketones. 

If, apart from the halide anion, other nucleophiles are present, the reaction may take a different course. For instance, in methanol the reaction shown in equation 28 took place. Initially formed l-bromo-2-methoxyhexene has rapidly reacted further to 52, which was hydrolysed to ketone 53. A similar behaviour was observed for bromine instead of chlorobromine ". With iodine in methanol a different product composition resulted terminal alkynes RC=CH (R = Bu, r-Bu and Ph) as well as 3-hexyne almost exclusively gave diiodoalkenes. The authors suggested that this addition of iodine follows a radical course. In the presence of silver nitrate, however, products expected for an ionic process were observed. 

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