Regioselective electrophilic formylation—3-substituted thiophenes as a case study

A variety of methods for regioselective formylation have been examined and exemplified with 3-methylthiophene. Optimal yields and regioselectivity for 2-formylation were obtained with N-formylpyrrolidine (11:1) although up to a 46:1 ratio could be obtained with MeOCHCl2:TiCl4, albeit in lower yield. Optimal 5-formylation (1:1.5) was obtained when using N-formylindoline:(COCl)2.