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Synthesis of some highly functionalized thiophene‐3‐carboxylates and alcohols
Author(s) -
Coppola Gary M.,
Damon Robert E.,
Yu Harvey
Publication year - 1996
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570330328
Subject(s) - chemistry , thiophene , aldehyde , wittig reaction , intramolecular force , derivative (finance) , dimethylformamide , lithium (medication) , formaldehyde , halogen , ring (chemistry) , organic chemistry , medicinal chemistry , catalysis , medicine , alkyl , solvent , financial economics , economics , endocrinology
Highly functionalized thiophenes are prepared by two methods. The first uses a lithium‐halogen exchange reaction on a trisubstituted 5‐bromothiophene 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 yields. 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, the benzyl mercaptan is dilithiated then reacted with an appropriate aldehyde to afford a 2‐mercapto‐2‐phenylethanol derivative 37 . Michael addition of 37 to 10 followed by oxidation of the hydroxyl group furnishes ketophosphonate 39 . An intramolecular Wittig‐type reaction produces the thiophene skeleton.