Aldehydes acetylides

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... 

Sodium acetylide and acetylenic Grignard reagents react with aldehydes and ketones to give alcohols of the type... 

You have already had considerable experience with caibanionic compounds and their- applications in synthetic organic chemistry. The first was acetylide ion in Chapter 9, followed in Chapter 14 by organometallic compounds—Grignaid reagents, for exanple—that act as sources of negatively polarized car bon. 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. 

Retrosynthetic cleavage of the indicated bond in 9 provides acetylenic aldehyde 23 as a potential precursor. It was anticipated that the action of a suitable base on 23 would result in the formation of an acetylide anion, a competent carbon nucleophile that could... 

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-... 

We see from these examples that many of the carbon nucleophiles we encountered in Chapter 10 are also nucleophiles toward aldehydes and ketones (cf. Reactions 10-104-10-108 and 10-110). As we saw in Chapter 10, the initial products in many of these cases can be converted by relatively simple procedures (hydrolysis, reduction, decarboxylation, etc.) to various other products. In the reaction with terminal acetylenes, sodium acetylides are the most common reagents (when they are used, the reaction is often called the Nef reaction), but lithium, magnesium, and other metallic acetylides have also been used. A particularly convenient reagent is lithium acetylide-ethylenediamine complex, a stable, free-flowing powder that is commercially available. Alternatively, the substrate may be treated with the alkyne itself in the presence of a base, so that the acetylide is generated in situ. This procedure is called the Favorskii reaction, not to be confused with the Favorskii rearrangement (18-7). ... 

On the other hand, following the same sequences from the differently protected serine-derived nitrone 168, through the formation of hydroxylamines 169, C2 epimers of carboxylic acid and aldehydes are obtained, i.e., (2S,3R)-170 and (2S,3R)-171. Moreover, the syn adducts 164 were exclusively obtained in the addition of Grignard reagents to the nitrone 163, whereas the same reactions on nitrone 168 occurred with a partial loss of diastereoselectivity [80]. Q, j6-Diamino acids (2R,3S)- and (2R,3R)-167 can also be prepared from the a-amino hydroxylamines 164 and 169 by reduction, deprotection and oxidation steps. The diastereoselective addition of acetylide anion to N,N-dibenzyl L-serine phenyhmine has been also described [81]. 

Even if hundreds of chiral catalysts have been developed to promote the enantioselective addition of alkylzinc reagents to aldehydes with enantioselectivities over 90% ee, the addition of organozinc reagents to aldehydes is not a solved problem. For example, only very few studies on the addition of vinyl groups or acetylides and even arylzinc reagents to aldehydes have been published, in spite of the fact that the products of these reactions, chiral allylic, propargylic and aryl alcohols, are valuable chiral building blocks. 

The facility with which the transfer of acetylenic groups occurs is associated with the relative stability of the ip-hybridized carbon. This reaction is an alternative to the more common addition of magnesium or lithium salts of acetylides to aldehydes. 

Various catalytic or stoichiometric asymmetric syntheses and resolutions offer excellent approaches to the chiral co-side chain. Among these methods, kinetic resolution by Sharpless epoxidation,14 amino alcohol-catalyzed organozinc alkylation of a vinylic aldehyde,15 lithium acetylide addition to an alkanal,16 reduction of the corresponding prochiral ketones,17 and BINAL-H reduction18 are all worth mentioning. 

The stereospecific reduction of a 2-butyne-l, 4-diol derivative and silver( I)-mediated cyclization of the resulting allene were successively applied to a short total synthesis of (+)-furanomycin 165 (Scheme 4.42) [68], Stereoselective addition of lithium acetylide 161 to Garner s aldehyde in the presence of zinc bromide afforded 162 in 77% yield. The hydroxyl group-directed reduction of 162 with LiAlH4 in Et20 produced the allene 163 stereospecifically. Cyclization followed by subsequent functional group manipulations afforded (+)-furanomycin 165. 

Metal complexes such as 337 of various butadienylallenes have been obtained in a straightforward manner from the aldehydes 336 by first reacting these with lithium acetylides and subsequently converting the obtained propargyl alcohols into allenes in the usual way (see Scheme 5.50 and earlier) [140],... 

Sodium acetylides are the most common reagents, but lithium, magnesium and other metallic acetylides have also been used. A particularly convenient reagent is lithium acetylide-ethylene diamine complex. Alternatively, the substrate may be treated with the alkyne itself in the presence of a base, so that the acetylide is generated in situ. 1,4-Diols can be prepared by treatment of aldehyde with dimetalloacetylenes. 

A set of 12 C-glycosyl asparagines has been synthesized from lithium C-glycoside acetylides and the Gamer aldehyde 169.[529]... 

HC=CCH(Ph)OH, b.p. 110 C/10 mmHg, nD(20 ) 1.5505, from UOCH.TMEDA-THF-hexane and PhCH=0 aliphatic aldehydes RCH=0, with R > C3H7 presumably can also be ethynylated with this stabilized acetylide. 

The non-enolizable benzaldehyde can be ethynylated with excellent results by simply introducing it into a cooled solution of lithium acetylide in liquid ammonia which contains an excess of dissolved acetylene. The advantage of cooling the ammoniacal solution below its b.p. (-33 C) is that the acetylene gas need not be introduced continuously during the addition of the aldehydes several liters of acetylene dissolve in the ammonia at temperatures below -40 C. Formation of the diol PhCH(OH)feCCH(OH)Ph is effectively suppressed by the excess of acetylene, and therefore a rapid addition of the aldehyde is possible. 

Besides electrophilic addition, terminal alkynes also perform acid-base type reaction due to acidic nature of the terminal hydrogen. The formation of acetylides and alkynides (alkynyl Grignard reagent and aUcylnyllithium) are important reactions of terminal alkynes (see Section 4.5.3). Acetylides and alkynides undergo nucleophilic addition with aldehydes and ketones to produce alcohols (see Section 5.3.2). 

The substance is stable at ordinary temperatures and up to 100°C. Like cupric acetylide it decomposes on being heated in hydrochloric acid (Berthelot [102], Sabaneyev [107]). A solution of potassium cyanide also causes decomposition with the loss of acetylene. Makowka [108] showed that aldehyde-like compounds are formed from cuprous acetylide on reaction with a 30% solution of hydrogen peroxide. 

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