Lithium-mediated

The enolates derived from 2,6-disubstituted phenyl propionates appear to exhibit the higliest levels of threo aldol diastereoselection yet reported for lithium-mediated condensations (33). These substrates should enjoy widespread use in stereoselective synthesis. 

As shown in Scheme 23, the lithium-mediated anti aldol reaction of the aryl ester 97 and aldehyde 98 gave the expected Felkin-Anh adduct 112 (30 ldr) [147, 148],... 

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. 

An anti aldol reaction with Felkin control was now needed to couple the two spiroacetal fragments and generate the correct stereochemistry at C15 and C f, of the spongistatins. A study of the individual fragments indicated that while the enolate showed little facial selectivity, the aldehyde component had a considerable bias for the desired Felkin product. Best results were obtained with the lithium-mediated aldol coupling, which gave adduct 104 in good yield and acceptable selectivity [56 c]. 

As shown in Scheme 9-57, the Ci-Cf, ketones 202 and 203 have both been prepared by aldol chemistry. The synthesis of ketone 202 used the Braun auxiliary 204 in a lithium-mediated aldol reaction and afforded adduct 205 in 75% yield and 98% ds [75]. This synthe.sis can be compared with the related Reformatsky reaction of imide 206, again controlled by an auxiliary attached to the enolate... 

A popular aldol connection has been a syn reaction to form the C(,-Cj bond (Scheme 9-59). The lithium-mediated syn aldol reactions of ketone 202 were used extensively by the Schinzer group in their synthesis of epothilone A and B [75]. 

Mg enolates generated from Mg bisamides can be used in aldol addition reactions with alkyl, aryl, and cyclic ketones. As shown in Scheme 3.40, these reactions are significant in that the self-coupling of ketones in aldol reactions to give tertiary yS-hydroxyketones are also possible. More specifically, these transformations are achieved principally by the use of relatively high reaction temperatures between 25 °C and 60 °C. Such conditions are a notable departure from the widely used lithium-mediated aldol additions, where increasing the reaction temperature results in retro-aldol processes and also elimination of LiOH to give enone products [30]. 

Scheme 4.22 Lithium-mediated transmetalation of polyrotaxane 98 gives access to Co11 and Zn11 analogs 99 and 100.

Reaction of the ultrasonically generated alkyllithiums with carbonyl compounds provides an extremely facile route to secondary and tertiary alcohols in a lithium-mediated Barbier-type reaction. 

Similarly, a lithium-mediated reaction gives the tertiary alcohol (4). This constitutes the first step in the total synthesis of (+)-methylpentalenic acid via an intramolecular double Michael reaction [88] (Scheme 27). 

Araki and Butsugan have recently described the lithium-mediated allyla-tion of carbonyls by means of an allylic phosphate anion [91]. 

These results are corroborated by Boudjouk and Han s study of the equivalent lithium-mediated reaction [94, 95] with both trialkyltin and silicon coupounds. Nevertheless, the cross-coupling reaction occurs faster than Wurtz-type coupling in this case, and products were uncontaminated by... 

The first record of an intramolecular organometallic addition onto an arene deals with the lithium-mediated conversion of tolane (diphenylacetylene) into 1,2,3-triphenylnaphthalene (186, M = Obviously (Z,Z)-l,2,3,4-tetraphenyl-l,3-... 

Paterson et al. achieved the convergent synthesis of the immunosuppressive agent discodermolide 205 by using a lithium-mediated aldol reaction with a chiral aldehyde (Scheme 8.31). The 2,6-dimethylphenyl ester 200 was derived to -enolate 201 by employing lithium 2,2,6,6-... 

Seggio A, ChevallierF, Vaultier M, Mongin F (2(X)7) Lithium-mediated zincation of pyrazine, pyridazine, pyrimidine, and quinoxaline. J Org Chem 72 6602-6605. doi 10.1021/jo0708341... 

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