Organolithium synthetic reaction

Scheme 7.4 illustrates some of the important synthetic reactions in which organolithium reagents act as nucleophiles. The range of reactions includes S/v2-(ype alkylation (Entries 1 to 3), epoxide ring opening (Entry 4), and formation of alcohols by additions to aldehydes and ketones (Entries 5 to 10). Note that in Entry 2, alkylation takes place mainly at the 7-carbon of the allylic system. The ratio favoring 7-alkylation... 

The preparation of organolithiums by reaction (a) is of limited synthetic utility because the organomercurlals are prepared from other organometallic reagents, most often organomagnesium halides or organolithiums. In addition, reaction (a) is slow, although ultrasonic irradiation increases the rate. 

The phenyl sulfides available permit the synthesis of organolithium by reaction (c) (see Table 2), e.g., tertiary alkyllithiums that are not available from the corresponding halides and sulfur-stabilized vinyllithiums that serve synthetically as acyl anion equivalents. Also, the benzyl ether moiety is not cleaved when the substrate contains both this moiety and a thiophenol group, and bis(phenyl sulfides) may be treated with 1-2 equiv of Li metal to give the mono- or dilithiums, respectively. 

The organolithiums prepared by the cleavage of phenyl sulfides are contaminated with LiSCgHj, which may affect their reactivity. In synthetic reactions, however, the byproduct QHjSH, which has a pK, of 6.5, is removed. 

The most important synthetic reactions of Grignard reagents and organolithium compounds are those in which they react as nucleophiles and attack an unsaturated carbon—especially the carbon of a carbonyl group. 

In a useful synthetic reaction that was mentioned on p. 837, organic acids react with two equivalents of an organolithium reagent to give the corresponding ketone (Fig. 17.49). 

Organolithium compounds or sodium metal reacts with halosilanes to give organosilicon compounds. The synthetic reactions are shown in eqs. (8.10) and (8.11). 

Scheme 6.4 summarizes some examples of the important synthetic reactions in which organolithium reagents act as nucleophiles. In addition to this type of reactivity, the lithium reagents have enormous importance in synthesis as bases or lithiating reagents. In this context, the commercially available methyl, butyl, and r-butyl reagents are used most frequently. 

We saw in Chapter 17 that organolithium compounds reaction with Cu(I) to give Gilman reagents. Thus organolithium compounds are important synthetic intermediates. 

The most general synthetic route to ketones uses the reaction of carboxylic acids (or their derivatives) or nitriles with organometallic compounds (M.J. Jorgenson, 1970). Lithium car-boxylates react with organolithium compounds to give stable gem-diolates, which are decom-... 

Table 17.2 summarizes the reactions of aldehydes and ketones that you ve seen in earlier chapters. All are valuable tools to the synthetic chemist. Carbonyl groups provide access to hydrocarbons by Clemmensen or Wolff-Kishner reduction (Section 12.8), to alcohols by reduction (Section 15.2) or by reaction with Grignard or organolithium reagents (Sections 14.6 and 14.7). 

The (3-elimination of epoxides to allylic alcohols on treatment with strong base is a well studied reaction [la]. Metalated epoxides can also rearrange to allylic alcohols via (3-C-H insertion, but this is not a synthetically useful process since it is usually accompanied by competing a-C-H insertion, resulting in ketone enolates. In contrast, aziridine 277 gave allylic amine 279 on treatment with s-BuLi/(-)-spar-teine (Scheme 5.71) [97]. By analogy with what is known about reactions of epoxides with organolithiums, this presumably proceeds via the a-metalated aziridine 278 [101]. 

The report by Luche and coworkers that ultrasonic waves from a common ultrasonic laboratory cleaner aid the formation of organolithium and Grignard reagents and also improve the Barbier reaction spurred much of the current interest in the synthetic applications of ultrasound(lO) ... 

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