Acyllithium generation

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. 

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). 

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. 

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. 

The deprotonation of (trimethylsilyl)diazomethane with n-butyllithium afforded the lithium silyldiazomethane 37, which reacts with CO at — 78 °C to give an acyllithium 3855,56. This intermediate underwent nitrogen extrusion generating the silylynolate 39 used as ketenylating reagent (Scheme 9). 

In the case of the a-stannylmethyllithium 41, generated from tri-w-butylstannylmethyl iodide (40), it reacted with CO at — 78 °C to give the acyllithium 42. This intermediate underwent 1,2-migration at very low temperature (much faster than for the silyl group) to give the enolate 43, derived from the corresponding acyltin compound (Scheme 10)57. 

Acyllithium reagents, RCOLi, 11, 111. These unstable anions, when generated from RLi and CO at - 135° in the presence of a carbonyl compound (1 equiv.), can effect nucleophilic acylation to give acyloins. Since 1,2-addition of RLi is a competing reaction, acylation is favored when the carbonyl group is hindered and when R is secondary or tertiary. The anions also react with esters under the same conditions to give 1,2-diketones. ... 

It should be pointed out that every method mentioned above involves the in situ trapping of the generated acyllithium. Otherwise the reactions proceed in very complex manners. Thus far, essentially no examples of an acyllithium as a discrete intermediate are known. Some, in the form of cuprate or nickelate complexes, behave like a discrete acyl anion intermediate, as will be described later. 

Eq. (5.11)) [18]. This method has also been applied to aldehydes [16, 18]. A variation of the electrophile gave a cyclic compound (Eq. (5.12)). Similarly, the acyllithium, which is generated in situ, can be trapped by dialkyl disulfides (Eq. (5.13)) [19] and also by heterocumulenes such as carbon disulfide [20], isocyanates [21], isothiocyanate [21], and carbodiimides [22]. 

Recently, Kabalka devised very interesting reactions in which the generated acyllithium is protonated by a pro-nucleophile to give an aldehyde, which then is attacked by the nucleophile formed (Eqs. (5.18) and (5.19)) [25, 26]. 

Our second method involves the utilization of a cyclization reaction [Scheme 5-2(b)]. We examined reactions that generate the negative charge of an acyllithium on the termini of Ti-conjugation chains [32]. 

Syntheses of tellurol esters 3 are limited in comparison to thiol and selenol esters. A conventional preparative method is the reaction of tellurolate anions with acid chlorides or acid anhydride [113]. Co2(CO)8-mediated carbonylation of dichalcogenides (described in Sect. 3.1.10) is applicable to diphenyl ditel-luride, but the yields of tellurol esters are poor. They can also be obtained by transesterification of esters with z-Bu2AlTeBu. Reactions of tellurol esters 3 have not been extensively explored yet. However, generation of acyllithiums by Li-Te exchange is characteristic. They can be employed as acyl radical precursors in tin free radical reactions. 

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