Acyllithium

Negatively charged carbonyl species, which are referred to as carbonyl anions (e.g. acyl- and aroyllithium derivatives), represent one of the more reactive organic intermediates that heretofore has rarely been utilized in practical synthetic reactions [1]. The carbonyl anion is a strong nucleophile, and at the same time it is an electrophile since it has a carbonyl function which is electrophilic in nature. Therefore, reactions involving a carbonyl anion are not straightforward, and usually a complex mixture is obtained from a reaction. 

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Metalation of nonenolizable carbonyl groups.1 This lithium amide, which lacks -hydrogens, cannot reduce nonenolizable aldehydes or ketones but can metalate these substrates. Thus reaction of LTMP with trimethylacetaldehyde (1) evidently results in an acyllithium (a) as shown by formation of an acyloin (2, equation I). 

Murai and coworkers reported on operationally simple aldol reactions with lithium enolates generated from carbonylation of silylmethyl lithium species [57]. Upon 1,2-silicon shift, a-silyl acyllithium species can be stereo-selectively converted to (E) lithium enolates that undergo addition to aldehydes to give /3-hydroxy acylsilanes (Scheme 14). 

The most important application of organolithium reagents is their nucleophilic addition to carbonyl compounds. One of the simplest cases would be the reaction with the molecule CO itself, whose products are stable at room temperature. Recently, it was shown that a variety of RLi species are able to react with CO or f-BuNC in a newly developed liquid xenon (LXe) cell . LXe was used as reaction medium because it suppresses electron-transfer reactions, which are known to complicate the reaction . In this way the carbonyllithium and acyllithium compounds, as well as the corresponding isolobal isonitrile products, could be characterised by IR spectroscopy for the first time. 

In a first experiment a pressure of 2 bar of CO at — I00°C was applied to a saturated solution of n-BuLi in liquid xenon. Surprisingly, no free CO was detected, but a stretching vibrational mode of the carbonyl adduct of the lithium alkyl was observed at 2047 cm (triple-bonded CO group). Warming up to —30°C led to the appearance of a new v(CO) peak at 1635 cm (double-bonded CO group), while the IR band of the carbonyl adduct vanished. The new absorption was therefore attributed to the acyllithium compound, which also decomposed at slightly higher temperature (—20°C) (equation 1) . ... 

Even the starting acylsilane 39 can be easily prepared via a Brook isomerization by the reaction of silylmethyllithium 41 with carbon monoxide " °. Initially, the reaction gives the corresponding unstable acyllithium 42 which underwent the Brook isomerization affording the stable lithium enolate (equation 16). 

Ureas of anilines 84 can also be lithiated" The products are generally very hard to cleave, but quenching the intermediate organolithiums 85 with carbon monoxide generates acyllithiums 86 which cyclize to give isatins 87 (Scheme 40)" . 

Another type of acyllithium synthons was generated in situ from chloroimines. The naphthalene-catalyzed (4%) lithiation of chloroimines 93 in THF at —78 °C was followed by filtration of the excess of lithium, being then treated with an electrophile and finally hydrolyzed, to yield functionalized imines 94 (Scheme 40) . ... 

IN SITU GENERATION OF ACYLLITHIUM REAGENTS a-HYDROXY KETONES FROM KETONES 3-HYDROXY-2.2.3-TRIMETHYLOCTAN-4-0NE FROM PINACOLONE (4-Octanone, 3-hydroxy-2,2,3-trlmethyl-)... 

In situ generated acyllithium reagents not only can acylate ketones, but also can acylate aldehydes,3 esters,4 lactones,5 isocyanates and isothiocyanates,6 carbodiimides,7 carbon disulfide and carbonyl sulfide,8 organic disulfides,9 and trialkylchlorosilanes.10 For reviews, see references 11 and 12. This direct, nucleophilic acylation procedure, when applicable, makes unnecessary the usually... 

Acyltrimethylsilanes. The first intermediate in the reaction of CO with RLi is KCOl.i, but attempts to trap this intermediate with chlorosilanes have not been successful.2 Acyltrimethylsilanes can be obtained in high yield when the acyllithium Is generated in the presence of CISiR, (equation I). 

Direct Nucleophilic Acylation by the Low Temperature, in situ Generation of Acyllithium Reagents a-Hydroxyketones from Ketones Synthesis of 3-Hydroxy-2,2, 3-trimethyloctan-4-one from Pinacolone R. Hui and D. Seyferth, Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139... 

Hui, R. Seyferth, D. Direct nucleophilic acylation by the low-temperature, in situ generation of acyllithium reagents a-hydroxy ketones from ketones 3-hydroxy-2,2,3-trimethyloctan-4-one from pinacolone. Org. Synth. 1993, Coll. Vol. VIII, 343-346. 

Seyferth, D. Weinstein, R. M. Hui, R. C. Wang, W.-L. Archer, C. M. Synthesis of a-hy-droxy ketones by direct, low-temperature, in situ nucleophilic acylation of aldehydes and ketones by acyllithium reagents./. Org. Chem. 1992, 57, 5620-5629. 

Smith, K. El-Hiti, G. A. Hawes, A. C. Carbonylation of doubly lithiated N -aryl-N,N-dimethylureas a novel approach to isatins via intramolecular trapping of acyllithiums. Synthesis 2003, 2047-2052. 

R = n-.s-.f-Bu R = Alkyl, Aryl Scheme 13 Acyllithium addition to aldehydes... 

There is one important class of exchange which is unique to tellurium telluroesters such as 181 undergo tellurium-lithium exchange to generate the highly unstable acyllithiums such as 183.147 These must be formed in the presence of an electrophile - typically pinacolone (t-butyl methyl ketone 182) or they decompose. 

An oc-functionalised carbenoid intermediate 26 can be made from 25,37>38 and acyllithiums 28 and 30 are available from the carbamoyl chloride 27 and thiocarbamoyl chloride 29.39 Lithiated sugars may also be made from chloropyranosides (see below).40... 

Acyllithiums (e.g., 156) can be obtained by reacting telluro esters (e.g., 155) with alkyllithiums at low temperature (Scheme 91). The telluro esters (e.g., 155) are obtained by reaction of acyl chlorides with organotellurolate anions.249... 

The synthetic applications of acyllithiums, generated by reaction of organolithium compounds with carbon monoxide, by treatment with electrophiles started when Nudelman and coworkers found that phenyllithium reacted with carbon monoxide in the presence of alkyl bromides to yield diphenylalkylcarbinols24,27. a-Hydroxy-a-phenylacetophenone was also obtained resulting from the dimerization of the carbene intermediate of type 3. In the absence of electrophiles a,a-diphenylacetophenone was obtained in 94% yield, attributed to the dimerization of the corresponding aroyl anion radical28. 

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