Synthesis of some novel imidate derivatives of thiophene and furan: Investigations of their metallation properties and some synthetic applications

Article abstract of DOI:10.1016/S0040-4020(01)86710-7

Methyl N-methyl and methyl N-(2,4,6-trimethyl)phenyl-2-carboximidates of thiophene and furan have been synthesized in excellent yields by the reactions of sodium methoxide in methanol with the corresponding N-methyl- and N-(2,4,6-trimethyl)phenyl-2-carboxymidoyl chlorides, which in turn, were obtained from their respective secondary amides by refluxing in neat thionyl chloride. A thorough investigation into the directed lithiation properties of the these heteroaryl-2-imidates with various lithiating agents, solvents, and reaction conditions revealed almost exclusive C5-lithiation. This regioselectivity is in contrast to the C3-lithiation reported for the oxazolino functionality (a cyclic imidate). The synthetic utility of the C5-lithiated intermediate of methyl N-methyl-thiophene-2-carboximidate with various electrophiles is demonstrated. C3-Lithiation has been effected in the case of methyl N-methylthiophene-2-carboximidate when the C5-position is blocked with a removable trimethylsilyl group. Methyl thiophene-2-carboximidate, an N-unsubstituted imidate, was found to eliminate methoxide ion and undergo subsequent C5-lithiation to give 5-lithiothiophene-2-carbonitrile with LDA. n-Butyllithium gave rise predominantly to products resulting from nucleophilic addition to the nitrile group.