Alkynolate anions

Alkynolate anions.2 Treatment of the enolate anion 1 of a-chloroacetophenone with t-butyllithium (1.5-2.1 equiv.)3 in THF involves deprotonation to the dianion a followed by loss of Cl" and migration of the group on carbon to give the alkynolate anion b. The rearrangement was established by use of 3C. The anion b reacts with benzaldehyde to form the /Mactone c, which can be isolated as such or as the product 2 of hydrolysis. Quenching b with methanol affords the ester C6H5CH2COOCH3 (57% yield). 

There is substantial recent interest in the preparation and chemistry of alkynolate anions. In 1982 Kowalski and coworkers found a general approach to alkynolate anions... 

Several less general approaches to alkynolate anions have also been reported in the literature ". Trimethylsilylethynolate (13) can be generated by deprotonation of ketene... 

The reactions of alkynolates with alcohols leading to esters 26 also imply the intermediate formation of ketenes (equation 18). However, initial formation of ynols resulting from the O-protonation of the alkynolate anion and subsequent rearrangement to ketenes cannot be excluded. 

The anionic complexes (50) are obtained from the group VI carbonyl and the dilithium derivatives of the hydroxyalkynes HC=CCR2(OH) subsequent protonation or acylation affords propadienylidene (51) or carbene (52) complexes by complex cyclization and addition reactions (Scheme 3) (28). Attempts to obtain the dimethyl complex by reaction of the chromium alkynolate dianion with COCl2 gave only polymeric material. More stable complexes were obtained with R = aryl (73). 

Stable esters coming formally from alkynols and carboxylic, sulphonic or dialkyl phosphoric acids were prepared for the first time via alkynyliodonium salts with the corresponding anion. Several alkynyl carboxylates were obtained by anion exchange of alkynyl iodonium tosylates the initially formed salts, PhI+C=CR RCO2, were converted spontaneously into the esters on elution through a chromatographic column packed with an anion-exchange resin (Pol+ArCOj) ... 

The reaction of amide chlorides with alcohols to yield alkoxymethyleneiminium salts, e.g. (91) and (92 Scheme 9), is important for the preparation of cations with bulky alkoxy groups, e.g. f-butoxy. These alcoholysis reactions demand the presence of salts with less nucleophilic anions in order to avoid dealkylation of the cations. This difficulty does not arise if the iminium hexachloroantimonates, which are obtained from the chlorides by addition of SbClj, are used for alcoholysis. A convenient route to / -unsubstituted salts (93 equation 54) is the alcoholysis of the formamide-benzoyl chloride adduct. The reaction of phenols with dimethylformamide chloride (27) affords aryloxymethyleneiminium salts (94 equation 55) which are hard to prepare by other methods. By addition of alkynols to the a-ha-loenamine (95) alkoxymethyleneiminium salts have been obtained (equation 56). ... 

The present procedure illustrates the use of added iodide anion to promote the Mannich cyclization of an alkyne to afford 3-alkylidenepiperidines. As illustrated in Table I a variety of nonbasic nucleophiles with nucleophilic constants T1-CH3I >5.8 are useful promoters of formaldiminium ion-alkyne cyclizations. Piperidines containing both endocyclic and exocyclic allylic unsaturation can be efficiently assembled in this way from readily available alkynol precursors (see Table 1). To the limits of f H NMR detection at 500 MHz all nucleophile-promoted cyclizations that form... 

Both types of reactivity of ynolate anion have been reported in the literature. The O-attack is typical for the reactions of lithium ynolates with trialkylchlorosilanes b24,25 dialkyIchlorophosphates. Lithium ynolates, generated as shown in equations 5-10, react with sterically hindered trialkylchlorosilanes in THF affording silyl ynol ethers as primary products (equation 12). However, in some cases the silyl ynol ethers are unstable at room temperature and isomerization to the more stable ketenes, or decomposition, occurs The ketene rearrangement usually occurs in reactions of lithium alkynolates with methyl substituted silyl chlorides a typical example of such a rearrangement is represented by reaction 13 ". ... 

One of the most practical ways to achieve chiral propargyl alcohol is to add acetylene anion to a carbonyl group in an enantiofacial manner. This art was well demonstrated by Mukayama et al. in 1979 using (2S,2 S)-2-hydroxymethyl-l-[(l-methylpyrrolidine-2-yl)methyl]pyrrohdine as a chiral ligand. The addition of lithium trimethylsilyl acetylide to benzaldehyde afforded the corresponding alkynol in over 92% optical yield. It is noted that the enantioselectivity of the present reaction depended predominantly on the trialkylsilyl group of the acetylene. Scheme 21.7 confirms these observations. 

One application of the corresponding enol ether formation is in the synthesis of D-decosamine 8.165 (Scheme 8.44), a deoxysugar that appears in many naturally occurring antibiotics. The required alkynol 8.162 was prepared from a 3-siloxyaldehyde 8.160 by addition of trimethylsilylacetylene anion. As the P-substituent exerted little stereocontrol over the new stereogenic centre, a chiral ligand was included in this... 

Two further syntheses of (+)-epiquinamide (2104), another of the (—)-enantiomer e t-2104 and one of the racemic alkaloid also pre-date the clarification of the natural product s absolute configuration. The route by Tong and Barker used (S)-(—)-pipecohnic acid (192) as chiral precursor (Scheme 267).After Boc protection of the amine and conversion of the carboxylic acid into the aldehyde 2121, diastereoselective addition of the lithium anion of TBS-protected propargyl alcohol gave mainly the (R)-alkynol (—)-2122 (69%) as well as the separable (S)-product, which was isolated as the cyclic carbamate (—)-2123 (5%). Attempts to invert the configuration of 2122 by treating its mesylate with sodium azide also... 

The transition metal-free addition of sodium phosphides to protected alkynols proceeds under mild conditions to selectively form the 1,1-addition products (Scheme 4.286) [73]. The alcohol was deprotonated prior to the addition of the anionic phosphorus reagent to ensure the selective addition to the alkyne. The lithium alkoxide was hydrolyzed after the P—C bond-forming reaction was obtained. The conditions were extremely mild, and moderate yields of the addition product were obtained. 

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