3-lithiated reaction with electrophiles

Semmelhack ME, Chlenov A (2004) (Arene)Cr(Co)3 Complexes Arene Lithiation/Reaction with Electrophiles. 7 21-42... 

Arene)Cr(C0)3 Complexes Arene Lithiation/Reaction with Electrophiles... 

Methylthiophene is metallated in the 5-position whereas 3-methoxy-, 3-methylthio-, 3-carboxy- and 3-bromo-thiophenes are metallated in the 2-position (80TL5051). Lithiation of tricarbonyl(i7 -N-protected indole)chromium complexes occurs initially at C-2. If this position is trimethylsilylated, subsequent lithiation is at C-7 with minor amounts at C-4 (81CC1260). Tricarbonyl(Tj -l-triisopropylsilylindole)chromium(0) is selectively lithiated at C-4 by n-butyllithium-TMEDA. This offers an attractive intermediate for the preparation of 4-substituted indoles by reaction with electrophiles and deprotection by irradiation (82CC467). 

Lithiation of 3,5-dibromopyridine with IDA and subsequent reaction with electrophiles provide 4-alkyl-3,5-dibromopyridines in high yield <96TL(37)2565>. The synthesis of aza-anthraquinones 39 via metallation of the pyridine ring of 38 was reported by Epsztajn <96T(52)11025>. 

Acyl hydrazides are useful precursors for the synthesis of 1,2,4-triazoles. Reaction of acyl hydrazides 149 with imidoylbenzotriazoles 148 in the presence of catalytic amounts of acetic acid under microwave irradiation afforded 3,4,5-trisubstituted triazoles 150 <06JOC9051>. Treatment of A-substituted acetamides with oxalyl chloride generated imidoyl chlorides, which reacted readily with aryl hydrazides to give 3-aryl-5-methyl-4-substituted[ 1,2,4]triazoles <06SC2217>. 5-Methyl triazoles could be further functionalized through a-lithiation and subsequent reaction with electrophiles. ( )-A -(Ethoxymethylene)hydrazinecarboxylic acid methyl ester 152 was applied to the one-pot synthesis of 4-substituted-2,4-dihydro-3//-1,2,4-triazolin-3-ones 153 from readily available primary alkyl and aryl amines 151 <06TL6743>. An efficient synthesis of substituted 1,2,4-triazoles involved condensation of benzoylhydrazides with thioamides under microwave irradiation <06JCR293>. 

Allylic and benzylic ethers can also be cleaved using an arene-catalyzed lithiation, so the corresponding organohthium intermediates could be generated. Thus, different benzylic ethers 49 were hthiated using a catalytic amount of naphthalene (5%) to yield the expected intermediates 50, which after reaction with electrophiles and final hydrolysis gave products 51 (Scheme 16) . ... 

Digeranyl and dibenzyl disulfides 78 were lithiated under DTBB catalysis (5%) in THF at 0°C to yield to the corresponding organolithinm compounds. Reaction with electrophiles at —30 to 0°C and final hydrolysis afforded the expected prodncts 20 (Scheme 31) . 

The naphthalene-catalyzed (3-12%) lithiation of deprotonated chloro phenols and anilides 236 performed with n-butylUthium in THF at 0 or —78 °C, respectively, gave the corresponding functionalized aryllithium intermediates 237 which, by reaction with electrophiles and final hydrolysis, yielded the corresponding polyfunctionalized molecules 238 (Scheme 79) . 

Lithiation of heteroaromatic compounds, especially nitrogen-containing systems, is an important methodology, because the lithiated intermediates can be easily functionalized in a regioselective manner by reaction with electrophiles. This process can be performed by deprotonation only at the ortho position of the heteroatom, but obviously the reaction is not possible at other positions . 

Whereas the halogen-lithium exchange is of limited importance for the generation of a-lithiated ethers, the reductive lithiation of 0/S-acetals has been applied more frequently, the versatility being enhanced by remarkable diastereoselective variants. Thus, a single diastereomer of the lithium carbenoid 52 results from the diastereomeric mixture 51 (equation 34) . Representative examples of a-lithiated ethers generated by this method and their reactions with electrophiles are given in Table 4. 

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