Selective Metallation of 3-Halothiophenes: Practical Methods for the Synthesis of 2-Bromo-3-formylthiophene

Abstract

Selective lithiation of 3-bromothiophene was accomplished under controlled conditions without formation of undesired thienyllithium compounds. A thienyl Grignard reagent derived from 2-bromo-3-iodothiophene was transformed into 2-bromo-3-formylthiophene in high selectivity by formylation with dimethylformamide (DMF) at optimal reaction temperature.

Keywords:

• 2-Bromo-3-formylthiophene
• 2-bromo-3-iodothiophene
• 3-bromothiophene
• thienyl Grignard reagent
• thienyllithium reagent

ACKNOWLEDGMENT

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. T. L. is grateful to the 21st Century Center of Excellence Program “Integrated Ecochemistry” for the support to his overseas internship at Osaka University.