Alkylithium

Leahy demonstrated that unsaturation at the 5-position of a 4-cyano-l,3-dioxane can lead to a reversal in selectivity [12] (Eq. 6). Alkylation of cyanohydrin acetonide 19 with benzyl bromide generated a 9 1 mixture of 20 and 21, with the flufz-isomer 20 predominating, in 57% overall yield. An alkylithium intermediate in which overlap with the methylidene tt orbital favors the axial configuration could account for this anomalous selectivity. 

Vinylic sulfones undergo the same reaction especially when allylic, benzylic or t-alkylithium reagents are employed. One case of a vinyl sulfone deserves special mention - . When phenyl trans-3-bromopropenyl sulfone is treated with certain Grignard reagents it undergoes an alkylating cyclization ... 

Since lithium amides (unlike alkylithiums) are unreactive toward most oxiranes at low temperature, they are widely used for /3-deprotonation reaction around room temperature whereas (bulky) alkyllithium bases are generally employed to generate oxiranyl anions at low temperature (—78 °C). 

Nonstabiiized lithiooxiranes can be prepared by the reaction of strong bases such as alkylithium reagents or lithium amides. However, as already discussed in a preceding section (Section II), the competition between a- and /3-deprotonation has to be adressed, and the issue of this competition is highly dependent on the structure of the starting oxirane as well as on the nature of the base used. These lithiooxiranes are very reactive species. In order to prevent their decomposition, they can be stabilized by a diamine ligand. Further stabilization can be obtained by a remote functionality. 

By the extension of the above-mentioned stereoselective asymmetric addition of alkylithiums to other organolithium reagents such as lithium salts of methyl phenyl sulfide, 2-methylthiazoline, trialkylsilylacetylene, N-nitroso-dimethylamine, and acetonitrile, chiral oxiranes (95) U1), thiiranes (96) nl), acetylenic alcohols (98) 112), and amino alcohols (97) U1) were readily obtained. 

A simplified radical chain mechanism for oxidation of polymeric organolithiums can be deduced from studies of the oxidation of simple alkylithiums (Scheme 1)S3), assuming the intermediacy of free radicals1. One often neglected facet of these oxidation reactions... 

The anionic polymerization of methacrylates and acrylates is poorly controlled even at low temperature, whenever initiated by alkylithium compounds, such as w-BuLi. In order... 

A more general method for arylation of terminal alkynes as well as electron-deficient alkynes is the Negishi Pd-catalyzed cross-coupling of aryl halides with alkynyl-zinc reagents. When using functionally substituted alkynylzincs, the deprotonation of 1-alkynes must be done with LDA instead of alkylithiums. 

Non-polar solvents, such as benzene or heptane, in which alkylithiums are more aggregated, increase the proportion of inversion. At the opposite extreme, complexing agents for the Li+cation, such as TMDA or, better, which generates free anions150, promote retention of configuration. Moreover, the addition of the lithium cryptand results in a 103-104-fold rate acceleration149. 

The chemistry of l-phospha-4-boracyclohexa-2,5-dienes has been further developed to include preparations of the less substituted derivative (44) and its 1-arsa analogue (45) which is formed as a 2 1 mixture with its dihydro counterpart (46) (Scheme 6). The chemistry of (5) includes its methanolysis to (47), its oxidation with chalcogens to phosphorus(V) compounds (48), and its conversion to F-methyl and ethyl derivatives (49) with potassium in DME followed by alkylation with alkyl halides. The. B-r-butyl derivative (50) is also available from the addition of the alkylithium, but attempts to prepare the corresponding 5-Me derivative were thwarted by the failure of the intermediate ate complex (51) to undergo demethoxylation <83JOM(250)33>. 

The direct conversion of dialkyl sulfates into alkylithium reagents provides an alternative route to the R-OH -> R-X - R-Li method. 

The use of the cyclitol, L-quebrachitol, as chiral auxiliary for ketone alkylation has been extended to additions of silyl enol ethers and silyl enol esters, providing a-hydroxyacid precursors, 269 with d.e. > 98% in most cases (Scheme 56). [Grignard, alkylithium and allylsilane additions to this substrate, Vol. 26, p. 319, ref. 93]. The same a-keto esters bearing this L-quebrachitol auxiliary undergo diastereoselective [3+2] cycloadditions with allylsilanes, providing a route to chiral functionalized tetrahydrofurans 270. ... 

Polar solvents such as ethers and amines react with organometallic initiators, as well as propagating polystyryl and polydienyl carbanions, to decrease the concentration of active centers (21-23). The rate of reaction with ethers decreases in the order Li > Na > K. For example, dilute solutions of poly(styryl)lithium in tetrahydrofuran (THF) at room temperature decompose at the rate of a few percent each minute. Alkyllithium initiators also react relatively rapidly with ethers the order of reactivity of organolithium compoimds with ethers is tertiary RLi > secondary RLi > primary RLi > phenyllithium > methyllithium > benzyllithium (21). An approximate order of reactivity of ethers toward alkylithium compounds is dimethoxyethane, THF > tetrahydropyran> diethyl ether> diisopropyl ether. Tertiary amines can also react with alkyllithium compoimds. The importance of these reactions can be minimized by working at lower temperatures (eg, <0°C) it is also advisable to use only the minimum amounts of ethers and other Lewis bases required as additives. 

In the reaction shown in eq. (3.10), as the reactivity of the lithium amide is lower than that of alkylithium, the pKa value of the organic group of 30 or less may be used [14,17]. 

Tosylhydrazones on reaction with alkylithium reagents give olefins in high yield. This new synthesis allowed for exas le the preparation of 16-androstene from androstan-17-one in quantitative yield.Reduction of carbonyl functions to methylene c ui be effected electrochemically or by treatment of the steroid ketones with powdered zinc in acetic anhydride saturated with hydrogen chloride at room temperature." ... 

Finally, an aza-Wittig rearrangement of acyclic enantio-enriched N,N-diallyllic a-amino alkylithium prepared via a tin-to-lithium exchange was reported, the process proceeding predominantly with inversion of configuration at the lithiumbearing carbon terminus [361]. 

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