The Scope and Limitations of Carboxamide-Induced β-Directed Metalation of 2-Substituted Furan, Thiophene, and 1-Methylpyrrole Derivatives Application of the Method of Syntheses of 2,3-Disubstituted Thiophenes and Furans

Article abstract of DOI:10.1021/jo00222a032

The effects of change of solvent, metalating agent, reaction time, and reaction temperature on the lithiation of N,N-diethylthiophene-2-carboxamide and of the N-tert-butyl-2-carboxamide derivatives of furan, thiophene, and 1-methylpyrrole are explored, and optimum conditions are established for ring β-directed metalation.The tertiary carboxamido group is less effective in this context than the secondary amide function and appears to be of limited value in these heteroaromatic systems.The high metalation levels achievable with the furan and thiophene secondary amides allow high-yielding syntheses (through reaction of the lithiated intermediates with a wide range of electrophiles) of otherwise inaccessible 2,3-disubstituted derivatives.The synthetical value of the methodology appears to be limited only by the forcing conditions required for amide hydrolysis.