SYNTHESIS OF SOME HIGHLY FUNCTIONALIZED THIOPHENE-3-CARBOXYLATES AND ALCOHOLS

Highly functionalized thiophenes are prepared by two methods. The firs t uses a lithium-halogen exchange reaction on a trisubstituted 5-bromo thiophene 25 to generate the corresponding 5-lithiothiophene 26 which is then reacted with either dimethylformamide or formaldehyde to give the 5-formyl 28 or 5-hydroxymethylthiophene derivative 31 in good yiel ds. These are further transformed to other tetrasubstituted thiophenes . The second method assembles the thiophene ring from three components : a benzyl mercaptan, an aldehyde, and a vinylphosphonate 10. Thus, th e benzyl mercaptan is dilithiated then reacted with an appropriate ald ehyde to afford a 2-mercapto-2-phenylethanol derivative 37. Michael ad dition of 37 to 10 followed by oxidation of the hydroxyl group furnish es ketophosphonate 39. An intramolecular Wittig-type reaction produces the thiophene skeleton.