Lithium enolates, homologation

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) °. 

Homologation reaction of lithium enolates with bis(iodomethyl)zinc (58) yields a homoenolate, namely the organozinc derivatives bearing a carbonyl group at the /3 position (Scheme 6)55. Treatment of the lithium enolate of cyclohexanone, generated from the silyl... 

Carbon-centered nucleophiles can also be used to advantage in the reaction with epoxides. For example, the lithium enolate of cyclohexanone 96 engages in nucleophilic attack of cyclohexene oxide 90 in the presence of boron trifluoride etherate to give the ketol 97 in 76% yield with predominant syn stereochemistry about the newly formed carbon-carbon bond <03JOC3049>. In addition, a novel trimethylaluminum / trialkylsilyl triflate system has been reported for the one-pot alkylation and silylation of epoxides, as exemplified by the conversion of alkenyl epoxide 98 to the homologous silyl ether 99. The methyl group is delivered via backside attack on the less substituted terminus of the epoxide <03OL3265>. 

Examples of metal hydride and organometallic additions include reactions of lithium hydride and sodium hydride with acetaldehyde and its homologs [145-147], reactions of methyllithium and methylcopper with acrolein [148], and aldol additions of lithium enolates [125]. The geometry of the four-center, cyclic transition states for such additions seems to depend on the size of the metal atom (see Schemes 6.16 and 6.17). 

Two new, general methods of one-carbon homologation have been reported. Treatment of a cyclic ketone (the method is equally applicable to acyclic systems) with dichloromethyl-lithium followed by n-butyl-lithium results in formation of a j8-oxido carbenoid which decomposes smoothly to the lithium enolate of the next higher ring homologue, chlorinated at the a-carbon (Scheme 36)." Substitution of... 

High diastereofacial selection has been found in condensations between a-methyl-aldehydes (250) and the dithioacetate enolate (251) the syn-isomers (252) predominate in these and homologous condensations using the lithium enolate of ethyl... 

A large variety of propionic acid esters and higher homologs having a chiral alcohol moiety have been used in additions to aldehydes [56, 57]. It turned out, however, that the lithium enolates result in only moderate simple diastereoselectivity and induced stereoselectivity, in contrast with the corresponding boron, titanium, tin, or zirconium enolates and silyl ketene acetals, with which stereoselectivity is excellent. The same feature has been observed in enolates derived from chiral amides and oxazolidinones, as... 

Known bicyclo[4.3.1]enone 15758 was converted into vinylsilane 158 with bis(trimethylsilyl)methyl lithium.55 Diene 158 underwent selective ozonolysis at the cis-olefin under conditions to produce differentially oxidized termini 90 alde-hydo-ester 159 was homologated with a phosphine oxide anion91 to enol 160. Subsequent hydrolysis of 161 provided substrate 162, which after tandem ozonolysis-acidification gave racemic 6,9-desmethyl analogue 155. Unfortunately, initial efforts failed to resolve 155 into its two optical isomers with cellulose triacetate.92 However, the antimalarial activity of racemate 155 is intriguing, as discussed in a later section. 

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