Lithium alkynolates synthesis

Reaction of lithium alkynolates with alcohols is especially useful for organic synthesis as a method of ester homologation . In this case ethyl esters of carboxylic acids 27 are used for the generation of lithium alkynolates in a multistep one-pot procedure (equation 19). Subsequent ethanolysis of lithium alkynolate in the presence of HCl gives homologated esters 28 in good yield. 

More recently we have reported the preparation of alkynyl esters by the reaction of lithium alkynolates with the corresponding acid chlorides (equations 14 and 15, Section II.B.2). This method works well for the synthesis of alkynyl phosphates, however, it has only limited applicability in the preparation of alkynyl carboxylates. ... 

Rossi, R., and A. Carpita Insect pheromones Stereoselective reduction of p- orco-alkynols to corresponding ( )-alkenols by lithium tetrahydroaluminate. Synthesis 1977, 561—562. 

Acetylenic precursors employed in the syntheses of sugars may be divided into three groups (a) aldehydes (usually in the form of acetals), (b) alkyl alkynyl ethers, and (c) alkynols or alkynediols. Some of them are commercially available (for example, 2-butyne-l,4-diol), and others are prepared by Grignard-type reactions between 1-alkynylmag-nesium halides or lithium alkynes and suitable aldehydes, ketones, or epoxides. In this way, the synthesis of substrates having the desired number of carbon atoms, as well as the necessary functional groups, can be achieved. The next step consists in partial saturation of the triple bond to afford the desired cis- or trans-alkene. ct.s-Alkene systems... 

Reduction of la-alkynols to (E)-alkenols." This reaction is often one step in the synthesis of insect pheromones. Sodium in liquid ammonia is generally preferred for this reduction (5, 590). An alternative, general method is reduction with a large excess of lithium aluminum hydride in diglyme-THF. 

The synthesis of fragment B will be done according to Scheme 3. The known hexacarbonyldicobalt complexed alkyne (12) will be prepared according to the work done by Krafft and co workers. First, 3-butyn-l-ol (13) will be converted to its rerr-butyldimethylsilyl (TBS) ether by treating a mixture of (13) with TBS-Cl in triethylamine and DMAP. Treatment of the protected alkynol with 5ec-butyl lithium in THF followed by low temperature quench with ethyl chloroformate yields the alkynoate (14). The alkynoate is then complexed with dicobaltoctacarbonyl in petroleum ether to yield (12) in excellent yield. 

A one-carbcMi ring enlargement approach for the synthesis of 8-lactones has been developed by Satoh and Kurihara [123] (Scheme 76). Reaction of the lithium carbanion of chloromethyl phenyl sulfoxide with lactone 336 afforded a diastereo-meric mixture of the hemiacetal 337. Treatment of this adduct with three equivalents of KH in THF generated potassium enolate 338, which on addition of four equivalents of t-BuLi underwent an alkylidene carbenoid rearrangement to give alkynolate 339. Protonation of 339 by the addition of sulfuric acid facilitated the formation of m-hydroxy ketene 340, which underwent an intramolecular cyclization to afford 8-lactone 341. 

The reaction of monodeprotonated [ C2]acetylene with carbonyl compounds has been exploited as a means of extension of the carbon chain of various terpenes and steroids by two [ " C]carbon atoms. In the simplest case, reaction of potassium [ C2]acetylide with steroid ketone 1 and subsequent acid catalyzed cleavage of the enol ether protecting group gave 17a-[ C2]ethynyltestosterone (2). The sequential addition of deprotonated [ C2]acetylene to carbonyl compounds opens access to symmetrical or unsymmetrical [2,3- C2]alkyn-l,4-diols is exemplified in the synthesis of all-tran -/3-[15,15 - C2]-carotene ([ C2]provitamin A). Thus, treatment of lithium [ C2]acetylide with terpene aldehyde 2 followed by double deprotonation of the resultant alkynol 4 and reaction with a second equivalent of 3 provided alkyne-l,4-diol 5 the requisite key intermediate. Subsequent acid-catalyzed dehydration of 5 followed by Lindlar s catalyst-mediated partial hydrogenation and photoisomerization afforded the final product". ... 

Stereoselective reduction of P- or (o-alkynols to corresponding ( )-alkenols has been achieved by Rossi and Carpita 646) with lithium aluminum hydride. Fyles et al. 647,648) have reported further applications of polymer supports in the synthesis of sex attractants. 

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