Acyl-lithium

The reactivity of lithium enolates has been explored in a theoretical study of the isomers of C2H30Li, such as the lithium enolate, the acyl lithium, and the a-lithio enol. Imides containing a chiral 2-oxazolidine have been employed for enantioselective protonation of prochiral enolates.A degree of kinetic control of the product E/Z-enolate ratio has been reported for the lithiation of 3,3-diphenylpropiomesitylene, using lithium amides/alkyls. " °... 

In the carbonylation reactions, further reaction of the acyl lithium compounds with carbon monoxide can occur, but clean reaction can be achieved if the lithium amide is first converted to a copper derivative (Scheme 130) (79JOC3734). In the case of morpholine, reaction with allyl bromide gave a 93% overall yield of the amide product. 

IN SITU GENERATION OF ACYL-LITHIUM REAGENTS a-HYDROXY KETONES FROM KETONES ... 

A further efficient preparation of these silyl enol ethers proceeds through an intramolecular 1,2-silicon shift in an a-silyl acyl lithium substrate (8), prepared from an a-lithiosilane (Scheme 23)". This method appears very simple to carry out, and produces the silyl enol ethers in good yields with high isomeric purity (usually, E isomer > 90% of mixture). 

Perhaps the most direct method of synthesizing an acyl silane is by reaction of an acyl lithium, prepared by carbonylation of an alkyl lithium at —110°C, with a silicon electrophile, illustrated in Scheme 28106,107. Although this method is successful for a variety of alkyl acyl silanes in moderate yields, low temperatures must be used, and the method is not suitable for aryl acyl silanes. 

Acyl anions (RC(=0)M) are unstable, and quickly dimerize at temperatures >-100 °C (Section 5.4.7). These intermediates are best generated by reaction of organolithium compounds or cuprates with carbon monoxide at -110 °C and should be trapped immediately by an electrophile [344—347]. Metalated formic acid esters (R0C(=0)M) have been generated as intermediates by treatment of alcoholates with carbon monoxide, and can either be protonated to yield formic acid esters, or left to rearrange to carboxylates (R0C(=0)M —> RC02M) (Scheme 5.38) [348]. Related intermediates are presumably also formed by treatment of alcohols with formamide acetals (Scheme 5.38) [349]. More stable than acyl lithium compounds are acyl silanes or transition metal acyl complexes, which can also be used to perform nucleophilic acylations [350],... 

Finally, an organic variant of acyl-protected compounds was recently proposed by Palomo and coworkers, who introduced the camphor-masked acyl lithium-mediated eno-late to produce /3-hydroxyketones or acids in 70 to 80% yield and high enantiomeric excesses (Scheme 113)560,561. Interestingly, for unprotected camphor derivatives (R2 = H), the stereoselectivity was dramatically improved by adding six equivalents of lithium chloride. 

Acyldihydrocodeinones (146) were made in a similar manner. The 8/3-(trans-1 -oxo-2-butenyl)- and 8/3-benzoyl derivatives were prepared from protected acyl lithium cuprates, and the 8/3-methylcarbonyl- (146) from the lithium bis(a-ethoxyvinyl) cuprate with codeinone, followed by mild hydrolysis of the intermediate, 147. Preparation of 8/3-t-alcohols may be achieved from 147 after reduction of the ring carbonyl, treatment with an appropriate alkyl lithium to 148, and oxidation back to a ketone, 149. 

The yields in these reactions are not wonderful and most syntheses planned with acyl anion or d1 synthons are realised with one of the reagents we are about to describe rather than with acyl-lithiums. Things may change as understanding of these rather reactive intermediates develops. There are three main types of acyl anion equivalent reagents which can be considered as modified acetals, that is protected aldehydes, masked carbonyl compounds such a nitroalkanes, and substituted vinyl-lithiums. The rest of this chapter will be devoted to these reagents. 

Acyl-lithiums and their Equivalents. Details have appeared of the preparation of di-isopropylcarbamoyl-lithium (LiCONPr a) by reaction of di-isopropylformamide with t-butyl-lithium. Lithiated dithioacetals, particularly those derived from dithians, continue to be popular. Alkylations of such species have been important reactions in syntheses of 25-hydroxycholesterol, pyrenophorin and vermiculin," and several chain-elongated sugars. 2-(3,3-Dialkoxypropyl)-l,3-dithians may be converted via their lithiated derivatives into protected 2-hydroxycycIobutanone derivatives (Scheme 1), themselves potential synthons for 1,4-diketones and cyclopentenones. ... 

Figure 6.6 Product-ion ESI-MS mass spectra of sodiated triacylglycerol species after CID. Product-ion mass spectra of lithiated 16 0-18 1-20 4 (a) and 18 1-18 1-20 4 TAG (b) were acquired with collision energy at 32 eV and collision gas pressure at 1 mTorr. The tandem MS mass spectra displayed abundant fragment ions corresponding to the neutral losses of either fatty acids or fatty acyl lithium salts from TAG species.

Acylsilanes are yet another class of valuable synthetic intermediates, and new methods for their synthesis are always welcome. In the first of several examples reported this year, the silyl allene (168) has been used as a common intermediate for the preparation of a diverse range of acylsilanes with a,p-olefinic, a,p-acetylenic, and a-keto substituents. Alkyl-substituted acylsilanes are now available via a high-yielding process in which an acyl-lithium (generated in situ from an alkyl-lithium and CO) is trapped by MeaSiCl. Cyclic acylsilanes have been prepared from cyclic vinylsilanes by way of an epoxidation-reductive ringopening-oxidation sequence. ... 

Acyl-lithiums and their Equivalents. Acyl-lithiums are amongst the most sought-after synthons, but to date they have been synthesized directly only for amide types (1). Thus, (1 = Pr ) has been obtained by the reaction of AW-bis(2-propyl)... 

Scheme 4 illustrates the application of another selenium-stabilized species, a formyl anion equivalent, in the synthesis of aldehydes. a-Metallated enamines, formed by reaction of a-chloroenamines with Li metal, are also acyl-lithium equivalents. ... 

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