Acyllithium compounds

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) . ... 

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. 

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. 

The reaction of aromatic orf/zo-substituted imidoyllithiums 56 with carbon monoxide and methyl iodide afforded li/-isoindole derivatives 61 in moderate yields (Scheme 16)77. In this process the formation of an acyllithium 57 was proposed to occur which, after formation of intermediate 58, cyclized to give the compound 59. The rearrangement of the alkyl group giving the aromatic product 60, followed by quenching with methyl iodide at — 78 °C, gave indolines 61. 

Methoxy(phenylsulfanyl)(trimethylsilyl)methyllithium 324 has been used as acyllithium and, depending on the electrophile and the deprotection conditions, it can transfer the acyltrimethylsilyl, the methoxycarbonyl or the (phenylsulfanyl)carbonyl group. By alkylation of intermediate 324 with primary alkyl iodides, bromides and chlorides in the presence of HMPA, followed by oxidation of compound 325 with NaI04, acylsilanes... 

In the case of aldonolactones, different lithiated trithioorthoesters 496-498 and 501 were essayed. The intermediate 496 was the most efficient acyllithium, allowing the formation of methyl 2-aldulosonates after mercury(II)-promoted methanolysis. Scheme 134 illustrates the preparation of compound 511 from the corresponding lactone714. 

Lithiated cyclic enamines 691 " 5 996 and amidines 692989,997 have been prepared by deprotonation of the corresponding heterocycles with f-BuLi in THF at — 78 °C, being allowed to react with several electrophiles. This methodology has been applied to the synthesis of pyrrolidine and piperidine derived compounds, intermediates 691 and 692 acting in these cases not as acyllithium equivalents. 

Dimethylated cumulenyllithium 783 has been prepared by deprotonation of the corresponding cumulenyl methyl ether with n-BuLi in ether or THF at — 30 °C. These anions reacted with aldehydes and ketones to produce the corresponding adducts (55-90% yield)1097. However, due to the instability of these types of compounds, they have not been used in organic synthesis as acyllithium equivalents. 

This volume, which complements the earlier one, contains 9 chapters written by experts from 7 countries. These include a chapter on the dynamic behavior of organolithium compounds, written by one of the pioneers in the field, and a specific chapter on the structure and dynamics of chiral lithium amides in particular. The use of such amides in asymmetric synthesis is covered in another chapter, and other synthetic aspects are covered in chapters on acyllithium derivatives, on the carbolithiation reaction and on organolithi-ums as synthetic intermediates for tandem reactions. Other topics include the chemistry of ketone dilithio compounds, the chemistry of lithium enolates and homoenolates, and polycyclic and fullerene lithium carbanions. 

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. ... 

The most varied types of organolithium compounds are nowadays used in syntheses. For example, 2-lithio-l,3-dithianes, as protected acyllithium derivatives (Eq. 288), are suitable reagents for hydroxyalkylation with oxiranes (Eq. 

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]. 

Jutzi reported the formation of enediol compounds from the reaction of trimethyl-silyl lithium with CO (Eq. (5.51)) [56]. As shown above, they proposed a mechanism involving the dimerization of a lithioxy carbene, which is an acyllithium tautomer (Eq. (5.51)). A similar reaction suggests the possibility of further insertion... 

Bis(trimethylsilylmethyl)thorium gave an enediol compound (Eq. (5.64)) [74], which is again similar to the one observed for the lithium counterpart as shown in Eq. (5.23). Another example of the similarity of the acyllithium to the lanthanide can be seen in the reaction of a vinylsamarium complex with CO (Eq. (5.65)) [75]. Formally, the reaction (Eq. (5.65)) is almost identical to the reaction shown in Eq. (5.30) and those in Scheme 5-3 for a vinyllithium. The mechanisms suggested for each reaction are different, but none of these have yet been studied further in detail. 

The remedy to avoid such mixtures is in situ trapping (Scheme 1-169). The organolithium is added slowly through a syringe needle across a rubber septum into a THF/DEE/PEN (tetrahydrofliran/diethyl ether/pentanes) solution saturated with carbon monoxide and and kept in the -135 to -110 °C range. In addition, this solution contains a suitable electrophile such as chlorotrimethylsilane, a carbonyl compound, or dicyclohexylcarbodiimide. Under such conditions, the acyllithium 225 is intercepted... 

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