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Cyclization Reactions of 1-Amino-5-trifluoromethyl-5-thienyl-1-azapenta-1,4-dien-3-ones under Superelectrophilic Conditions: Synthesis of Novel Benzothiophenols, Cyclopentenols and Dihydrodiazepinols



Trifluoromethyl-substituted 1-amino-5-thienyl-1-aza-1,4-dien-3-ones 5, which are accessible in good yields from keto esters 1 in a three-step procedure, undergo three different types of cyclization reactions upon treatment with a large excess of trifluoromethanesulfonic acid, depending on the substitution pattern. Thus, starting materials 5af without a halogen substituent at the 3-position of the thienyl subunit undergo 1,6-cyclization reactions (hydroxyannulation) to give benzothiophenol derivatives 6. In contrast, 5-(3-bromothienyl)-substituted compounds 5gj undergo Nazarov 1,5-cyclization reactions to produce cyclopentenols 7ad. Finally, 1-dimethylamino-substituted 1-azadienones 5k,l undergo 1,7-cyclization reactions to form novel dihydrodiazepinones 8a,b after tautomerization. On the basis of quantum chemical calculations we interpret these different types of multistep reactions to be cyclization reactions that proceed under superelectrophilic conditions through both mono- and dicationic intermediates. Electrophilic and pericyclic cyclization modes are discussed on the basis of the results of NICS calculations. Several of the compounds 6, 7 and 9 were characterized by X-ray diffraction.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)