Regio- and Chemoselective Synthesis of Fully Substituted Thiophenes

Org. Lett., 2009, 11, 446-448 published on 17.12.2008
Org. Lett.
A full functionalization of all four positions of the thiophene ring was achieved. Starting from readily available 2,5-dichlorothiophene, successive magnesiations of the 3- and 4-positions using TMPMgCl·LiCl furnish, after trapping with various electrophiles, 3,4-difunctionalized dichlorothiophenes. Subsequent dechlorination and metalation or magnesium insertion into the C-Cl bond provides fully functionalized thiophenes in high yields. An application to the synthesis of a thiophene analogue of Atorvastatin (Lipitor) is reported.
TU München