Regio- and chemoselective synthesis of fully substituted thiophenes.
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 x 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.
Piller
Fabian M
FM
Department Chemie und Biochemie, Ludwig-Maximilians-Universität, Butenandtstrasse 5-13, 81377 München, Germany.
Knochel
Paul
P
D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D008872:Microwaves; D010165:Palladium / Q000737:chemistry; D013237:Stereoisomerism; D013379:Substrate Specificity; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry
D013876:Thiophenes; D010165:Palladium; D002244:Carbon