Lithium diisopropylamide, reaction with amino-esters

Alkyl and arylmagnesium halides react with 2-methylquinoxaline by addition of one mole of reactant to the 3,4-bond. After hydrolysis the 2-alkyl- or 2-aryl-l,2-dihydro-3-methylquinoxalines (52) are obtained. When ethylmagnesium bromide is used a dimeric by-product (53) is also isolatedReaction of 2,3-dimethylquinoxaline with benzonitrile and lithium amide gives l-amino-l-phenyl-2-(3-methyl-2-quinoxalinyl)-ethylene (54). The mono- and dilithium salts of 2,3-dimethylquinoxaline have been generated from the quinoxaline by reaction with one or two equivalents of lithium diisopropylamide (LiNPr, respectively. These salts have been reacted with a variety of electrophilic reagents such as alkyl halides, aryl ketones, esters, and nitriles. " ... 

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... 

A typical reaction that uses an amino acid derivative involves initial conversion to an enolate anion. This nucleophilic species is then reacted with an alkyl halide or a carbonyl derivative. An example that produces a new amino acid is the reaction of the ethyl ester of n-benzyl glycine with lithium diisopropylamide to give the enolate. Subsequent reaction with the mixed anhydride shown below proceeded with displacement of acetate to give /.22J.13 Acid hydrolysis generated a P-keto amino acid, which decarboxylated under the reaction conditions to give 4-oxo-5-aminopen-tanoic acid 1.156, also known as 5-aminolevulinic acid). 

In one approach, an imine moiety was generated in situ by reaction of a methoxy carbamate with lithium diisopropylamide. This imine was then condensed with an ester enolate to give the amino-ester, protected as a carbamate. Reaction of 4,70 with lithium diisopropylamide gave imine 4.71, for example. Subsequent reaction with... 

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