Lithium enolates alkyllithium addition

Scheme 2.45 Diastereoselective formation of lithium enolates by addition of alkyllithium reagents to ketenes. In situ preparation of ketenes from BHT esters.

Finally, the addition of the carbanion of 1-chloroalkyl p-tolyl sulfoxides 154 to carbonyl compounds gave the adducts 155, which were treated with alkyllithium such as f-C4H9Li to afford the one-carbon homologated carbonyls compounds 158, from their lithium enolate forms 157, having an alkyl group at the a-position, via the carbenoid /S-alkoxides 156 (equation 53) °. 

By an alternative sequence 2-lithiation, reaction with an aldehyde, quaternisation, C-2-addition of an alkyllithium, and finally silver-promoted ring cleavage of the resulting dihydrobenzothiazole, the heterocycle can be made the means for the construction of a-hydroxyketones. Lithium enolates also add smoothly to benzothiazolium salts. ... 

Enolates can also be prepared by reaction of enol esters - - or silyl enol ethers with alkyllithium reagents. House has worked out a protocol wherein these enolates are allowed to react with aldehydes to give the corresponding aldols. Higher yields of aldol products are obtained when the lithium enolate is generated in ether or 1,2-dimethoxyethane (DME) by reaction of an enol acetate with methyllithium. Lower yields are obtained if the enolate is produced by reaction of a silyl enol ether with methyllithium. For the aldol reaction, ether or mixtures of ether and DME are superior to THF. Acceptable yields of aldol adducts are obtained in ether at low temperatures (-20 to -50 C). In the more polar solvents DME or THF, the addition of anhydrous ZnCh or MgBra results in higher yields. An example is seen in equation (13). The stereochemistry of this process is discussed in Section 1.6.5. 

Treatment of the potentially electrophilic Z-xfi-unsaturated iron-acyl complexes, such as 1, with alkyllithium species or lithium amides generates extended enolate species such as 2 products arising from 1,2- or 1,4-addition to the enone functionality are rarely observed. Subsequent reaction of 2 with electrophiles results in regiocontrolled stereoselective alkylation at the a-position to provide j8,y-unsaturated products 3. The origin of this selective y-deproto-nation is suggested to be precoordination of the base to the acyl carbonyl oxygen (see structures A), followed by proton abstraction while the enone moiety exists in the s-cis conformation23536. 

General methods for the preparation of a.jS-unsaturated iron-acyl complexes are deferred to Section D 1.3.4.2.5.1.1. examples of the alkylation of enolates prepared via Michael additions to ii-0 ,/ -unsaturated complexes prepared in situ are included here. Typical reaction conditions for these one-pot processes involve the presence of an excess of alkyllithium or lithium amide which first acts as base to promote elimination of alkoxide from a /f-alkoxy complex to generate the -a,)S-unsaturated complex which then suffers 1,4-nucleophilic addition by another molecule of alkyllithium or lithium amide. The resulting enolate species is then quenched with an electrophile in the usual fashion. The following table details the use of butyllithium and lithium benzylamide for these processes44,46. 

Directed lithiations of a,3- and -y.b-unsaturated amides " have been extensively studied. Illustrative examples are shown in Scheme 44. Prior complexation of the alkyllithium base with the amide carbonyl oxygen directs the base to the thermodynamically less acidic -position in a,3-unsaturated amide (31), which adds to benzophenone and subsequently lactonizes. Analysis of the NMR spectrum reveals that the organolithium added the benzophenone in the equatorial position. A Afferent kinetic deprotonation is seen in y,8-unsaturated amide (32), where -lithiation to form an allylic anion predominates over a-lithiadon to form an enolate. > Addition of the lithium anion to acetone affords poor regioselectivity, but transmetalation to magnesium before carbonyl addition yields a species which adds exclusively at the 8-position. ... 

Another auxiliary that became well known in enolate chemistry is chiral acyl iron complexes for alkylation, aldol reactions, and conjugate additions indeed, so-called Davies-Liebeskind enolates [60] can be generated either by deprotonation of alkanoyl complexes 124a or conjugate addition of strong nucleophiles like alkyllithium compounds or lithium amides to alkenoyl complexes 127. 

The ratio of enolate vj. vinylalkoxide approximates 3 1 when an alkyllithium is used as the reagent. The addition of potassium ter/-butoxide raises the selectivity to about 9 1 [1101] Obviously the increase in metal-oxygen bond polarity makes it energetically more rewarding to produce the resonance-stabilized enolates. Unfortunately the [1,4]- V5. [l,2]-selectivity diminishes again when a secondary or tertiary alkyl migrates. The ratio amounts to 2 5 for neat lithium compounds and 3 2 for potassium/lithium mixed metal species... 

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