Alkylation Orientation Rules in Conjugate Addition of Grignard Reagents to Nitropyrrole and Nitrothiophene Systems

Conjugate addition of various Grignard reagents to 1-alkyl-2-nitropyrroles and to 2-nitrothiophene has been investigated. 1-Alkyl-2-nitropyrroles undergo alkylation at 3 and 5 positions with prevalence of the latter isomer. On the contrary, in 2-nitrothiophene system, formation of the 3-isomer prevails. In both systems, a bulkier Grignard reagent favours the 5-isomer formation. This trend can be reversed increasing steric hindrance exerted by the 1-substituent of 2-nitropyrrole. 1-(Tri-isopropylsilyl)-3-nitropyrrole and 3-nitrothiophene give exclusively the 2-isomer. This rection allows 2-alkyl-3-nitrothiophenes and pyrroles to be synthesized with a one-pot procedure instead of the classical multi-stage reaction.