Highly selective 5-substitution of 3-methylthiophene via directed lithiation.
Lithiation of 3-methylthiophene with lithium 2,2,6,6-tetra-methylpiperidide (LiTMP) is highly selective at the 5-position, and reaction with a range of electrophiles gives high yields of the corresponding 2,4-disubstituted thiophenes, even when unhindered electrophiles are used.
Smith
Keith
K
Centre for Clean Chemistry, Chemistry Department, University of Wales, Swansea, Singleton Park, Swansea SA2 8PP, UK. k.smith@swan.ac.uk
Barratt
Mark Lewis
ML
D008094:Lithium / Q000737:chemistry*; D008745:Methylation; D008956:Models, Chemical; D009942:Organometallic Compounds / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry*; D013876:Thiophenes / Q000737:chemistry*
D009942:Organometallic Compounds; D010880:Piperidines; D013876:Thiophenes; D008094:Lithium