Organolithium compounds substitution

Addition of phenylmagnesium bromide to phthalazin-l(2//)-one or derivatives like 4-phenylphthalazin-l(2/f)-one, 4-phenylphthalazine-l(2/f)-thione and 2-substituted phthalazin-l(2//)-ones results in the formation of 1,4-diphenylphthalazines, while addition of organolithium compounds to phthalazin-l(2/f)-one gives the 4-substituted derivative. 

The reaction of tnfluoromethyl-substituted A -acyl umnes toward nucleophiles in many aspects parallels that of the parent polyfluoro ketones Heteronucleophiles and carbon nucleophiles, such as enarmnes [37, 38], enol ethers [38, 39, 40], hydrogen cyanide [34], tnmethylsilylcarbomlnle [2,47], alkynes [42], electron-nch heterocycles [43], 1,3-dicarbonyl compounds [44], organolithium compounds [45, 46, 47, 48], and Gngnard compounds [49,50], readily undergo hydroxyalkylation with hexafluoroace-tone and amidoalkylation with acyl imines denved from hexafluoroacetone... 

Metalation of Thiophenes with Organolithium Compounds (Nucleophilic Substitution on Hydrogen)... 

By the same principle, starting from the appropriate, metal-substituted, organolithium compound, products containing both tin and another metal have been synthesized, e.g.. 

Organomagnesium and organolithium compounds are strongly basic and nucleophilic. Despite their potential to react as nucleophiles in SN2 substitution reactions, this reaction is of limited utility in synthesis. One limitation on alkylation reactions is competition from electron transfer processes, which can lead to radical reactions. Methyl and other primary iodides usually give the best results in alkylation reactions. 

Although the resulting vinylallenes 48 were usually obtained as mixtures of the E and Z isomers, complete stereoselection with regard to the vinylic double bond was achieved in some cases. In addition to enyne acetates, the corresponding oxiranes (e.g. 49) also participate in the 1,5-substitution (Scheme 2.18) and are transformed into synthetically interesting hydroxy-substituted vinylallenes (e.g. 50) [42], Moreover, these transformations can also be conducted under copper catalysis by simultaneous addition of the organolithium compound and the substrate to catalytic amounts of the cuprate (see Section 3.2.3). 

Scheme 2.3S Formation of exocyclic allenes 103 by intra-molecular SN2 substitution of organolithium compounds.

Unsymmetrical dienynes react regioselectively with organolithium compounds at the less substituted double bond (Scheme 2.37). Thus, addition of n-butyllithium to 2-methylhexa-l,5-dien-3-yne (107) led after hydrolysis to vinylallene 108, whereas the corresponding carbolithiation of the linear isomer 109 furnished product 110 with 55% yield [68]. 

SN, reactions of primary stabilized organolithium compounds on polyalkylmethacrylates affords a very versatile synthetic route to model ketonic copolymers substitution is selective and quantitative up to DSm of 0.60,and it is easily monitored by the initial... 

The use of sterically hindered secondary organolithium reagents, such as (CgH jCH Li, drastically favors the O-alkyl scission of thejbster group (37) finally, organolithium compounds leading to non enolizable keto functions in the first step of substitution, such as C H Li, promote competitive and consecutive reactions resulting in complex copolymers of poorly defined structure (38,39) ... 

Elimination to yield alkenes can be induced thermally or by treatment with acids or bases (for one possible mechanism, see Figure 3.39) [138,206]. Less common thermal demetallations include the thermolysis of arylmethyloxy(phenyl)carbene complexes, which can lead to the formation of aryl-substituted acetophenones [276]. Further, (difluoroboroxy)carbene complexes of molybdenum, which can be prepared by treating molybdenum hexacarbonyl with an organolithium compound and then with boron trifluoride etherate at -60 °C, decompose at room temperature to yield acyl radicals [277]. 

Self-condensations are another set of important reactions of organolithium compounds. Tamao and Kawachi had reported that [(tert-butoxy diphenyl)silyl]lithium (20) exhibited ambiphUic character, and underwent a self-condensation reaction to give a [2- tert-butoxy)disilynyl]lithium derivative in THF as shown in Scheme 4, and also a nucleophilic substitution reaction with n-butyllithium . 

Therefore, the appearance of the C—Li bands at unexpected low wavenumbers and their behaviour upon isotopic substitution demonstrate that these bands represent complex modes of vibration in polymeric molecules rather than simple C—Li stretching motions (Figure 1). It is well known that organolithium compounds are strongly associated in solution Furthermore, the C—Li bands occurred in the mulls and solution spectra of ethyllithium at similar positions to those in the vapour spectra, namely in the region from 570 to 340 cm (Table 1) . In benzene solution the bands were found at 560 and 398 cm for CiHs Li and at 538 and 382 cm for CiHs Li. This seems to confirm the previous finding of Berkowitz and coworkers that ethyllithium is polymeric even in the vapour phase. ... 

Acyclic and cyclic sp -hybridized ketal-containing y-functionalized organolithium compounds can be generated using an arene-catalyzed Uthiation at low temperature. In the case of acyclic precursors 171 (R = H) it was necessary to lower the temperature to -90 °C in the Uthiation step under DTBB catalysis (4%) in order to avoid decomposition of intermediates 172. Final electrophilic substitution reaction of these intermediates with electrophiles occurred with retention of configuration at temperatures ranging between... 

A particular case for the generation of a y-substimted organolithium compound, derived from an imine, was used for the synthesis of 2-substituted pyrrolidines. DTBB-catalyzed (5%) lithiation of y-chloro imines 196 yielded, after hydrolysis, 2-substituted pyrrolidines 198, including nomicotine (R = H, R = 3-pyridyl). The corresponding y-nitrogenated organolithium intermediate 197 was probably involved (Scheme 68). ... 

For aU the chiral intermediates above mentioned (253, 257 and 258) the reaction with prochiral electrophiles (aldehydes or differently substituted ketones) gave a c 1 1 mixture of diastereomers so, as occurred in other chiral functionalized organolithium compounds, the asymmetric induction is practically non-existent. 

Configurational stability has also been confirmed for various metalated carbamates by Hoppe and coworkers. Remarkably, carbamate-protected alcohols such as 20 are deprotonated enantioselectively, when treated with i-butyllithium in the presence of (—)-sparteine. The lithium carbenoids like 21 (R = alkyl) thus generated turn out to retain their configuration (equation 11). Similar results have been obtained for a-lithiated amines and carbamate protected amines " . As a rule, dipole stabilization of the organolithium compounds in general also enhances the configurational stability of a-oxygen-substituted lithium carbenoids. 

The electrophile for the cyclization reaction of an a-amino-organolithium compound is not restricted to a terminal (or phenylthio-substituted) ahcene and examples have been reported using carboxylic amides, alkynes and allyhc ethers." " For example, Fautens and Kumanovic reported that treatment of the bicyclic stannane shown in Scheme 24... 

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