Heterocyclic compounds Lithium diisopropylamide

Due to the importance of azines and diazines in pharmaceutical industry and biorganic chemistry, the development of selective and efficient metallation protocols for substituted compounds has been the object of deep investigations.1 - The main difficulty in this context is that the 7r-deficient heteroaromatics undergo a facile nucleophilic addition to the azomethine bond with alkyllithiums.184-186 For this reason sterically hindered non-nucleophilic lithium amides (lithium diisopropylamide and lithium 2,2,6,6-tetramethylpiperidide)181 182 are usually employed in the selective deprotonation of heterocyclic compounds. In some cases the use of both unimetallic183 and... 

It was found that 1,3-diethoxycarbonylallene 231 readily enters [4 -I- 2] cycloaddition with heterocyclic dienes. The adduct (232) obtained from 231 and furan was easily converted into ketoester 233. Treatment of the latter compound with lithium diisopropylamide and benzenediazonium fluoroborate resulted in the formation of the a-phenylazo compound 234, which in turn underwent sodium borohydride promoted scission of carbon-carbon bond affording the C-glycosylic compound 235 ... 

The condensation of the anhydride 2 with bicyclic ketones of the heterocyclic series 47 under the influence of lithium diisopropylamide leads to angularly constructed compounds 48, also containing two heterocyclic rings in the molecule [27, 28],... 

Kim and coworkers have reported a synthetic route to diverse heterocyclic compounds through the nucleophihc addition of P-amino carbonyl compounds 79 to 3-halo-4-methoxybenzynes 78 (Scheme 12.25) [51]. The benzyne intermediate 78 was generated from 5-(3-halo-4-methoxyphenyl)thianthrenium perchlorates 77 upon treatment with lithium diisopropylamide (LDA) in THF at reflux. P-Amino carbonyl compounds, such as P-amino ketones, esters, amides and aldehydes, all react smoothly with benzyne 78 under the reported reaction conditions. Moreover, bis(2-aminophenyl) disulfide, 2-aminophenyl benzenesulfonate... 

Being treated with a mixture of lithium diisopropylamide and potassium t-butoxide, 3-fluoroquinoline (173, X=H, OCH2CH2CH2CH3) undergoes the selective metallation of the C-H bond at position 4 of the heterocyclic ring. This reaction allows one to alkylate the position 4 of 3-fluoroquinoline (Scheme 74) [12], 2-Bromo-3-fluoroquinoline (173, X=Br), derived from the reaction of 3-fluoro-quinolin-2(lH)-one with PBrs, is easily lithiated and transformed into 3-fluoro-quinolin-2-carboxylic acid 174 on treatment of 2-lithium compound with dry carbon dioxide [106],... 

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