Organolithium compounds hydrolysis

Lithium ion is commonly ingested at dosages of 0.5 g/d of lithium carbonate for treatment of bipolar disorders. However, ingestion of higher concentrations (5 g/d of LiCl) can be fatal. As of this writing, lithium ion has not been related to industrial disease. However, lithium hydroxide, either dHectly or formed by hydrolysis of other salts, can cause caustic bums, and skin contact with lithium haHdes can result in skin dehydration. Organolithium compounds are often pyrophoric and requHe special handling (53). 

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]. 

Another type of sp -hybridized S-oxido functionahzed organolithium compounds has been easily prepared from chloroacetic acid (149). After a double deprotonation with lithium diisopropylamide in THF at —78°C, a DTBB catalyzed (5%) hthiation in the presence of different carbonyl compounds as electrophiles at the same temperature followed by final hydrolysis afforded the expected S-hydroxy acids 151. The corresponding intermediate 150 was probably involved in the process (Scheme 54)" . 

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). ... 

Y = O) or —90°C (Y = NMe, S) gave the corresponding intermediates 427 resulting from a carbon-sulfur cleavage. Further reaction of these functionalized organolithium compounds with different electrophiles at the same temperature, followed by hydrolysis with water, yielded products 428 (Scheme 120) . 

The Wittig rearrangement of these anions afforded the alkoxides 35, which upon hydrolysis produced the alcohols 36. This type of reaction constitutes an alternative to new organolithium compounds that are difficult to obtain by traditional methods. 

Ketoenamines derived from chiral cyclic amines were found to react with Grignard reagents or organolithium compounds by a 1,2-addition. Subsequent hydrolysis gives R- (or (5)-a-hydroxycycloalkanones in high enantiomeric excess. The stereochemical selectivity is caused by different structures of the intermediate formed by complexation of the different organometallic compounds320 (equation 238). 

Cyclic alkyl aryl ethers lead also to functionalized organolithium compounds by reductive carbon-oxygen bond cleavage in arene-catalyzed lithiation process. Thus, the treatment of 2,3-dihydrobenzofuran (47) with an excess of lithium in the presence of a catalytic amount of DTBB in THF at 0°C gives the dianion (48) which after reaction with different carbonyl compounds and final hydrolysis with water leads to... 

Quinoline and isoquinoline undergo a set of reactions in which, in effect, a hydride ion is replaced by a strongly nucleophilic species. With organolithium compounds the initial adduct, on hydrolysis and mild oxidation, yields the corresponding alkyl or aryl derivative, and hydroxy or amino groups can be introduced by reaction with alkali metal (or alkaline earth) hydroxides or amides. 

Further, elemental phosphorus can be converted by Grignard reagents or organolithium compounds into metal phosphides which afford primary phosphines on hydrolysis phenylphosphine was obtained in this way in yields of up to 40% from phenyllithium and white phosphorus.214 In some circumstances cyclophosphines are formed on reaction of alkyl halides with the phosphide solutions obtained from elemental phosphorus.215... 

White phosphorus reacts with Grignard reagents and organolithium compounds, generating phosphides which give phosphines on hydrolysis phenyl-lithium yields up to 40% of phenylphosphine in this way.361 Alkylation by alkyl halides before hydrolysis leads to unsymmetrical tertiary phosphines.215... 

The Ziegler reaction (see p 278) with organolithium compounds leads exclusively to 2-alkyl- or 2-arylquinolines. For instance, 20 is produced with -butyllithium. After hydrolysis, the primary adducts (e.g. 16) yield stable 1,2-dihydroquinolines (e.g. 17) which can be dehydrogenated by nitro compounds. It is obvious that control of the RLi addition occurs through coordination, because even 2-substituted quinolines (e.g. 18) yield mainly 2-addition products (e.g. 19). 

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