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Formation of Highly Substituted Indenes through Acid Promoted Cyclodehydration with Nucleophile Incorporation
Annaliese S Dillon1, Daniel J Kerr1, Bernard L Flynn1
1Monash Institute of Pharmaceutical Sciences , Monash University , 381 Royal Parade , Parkville 3052 , Victoria , Australia.
Abstract:
Readily accessible 3-aryl-2-carboxypropenones (by Knoevenagel condensation) undergo acid promoted cyclodehydration with nucleophile incorporation to form highly substituted indenes. For stronger nucleophiles, nucleophile incorporation precedes cyclodehydration in a nucleophilic-addition-cyclodehydration (NAC) sequence. For weaker nucleophiles, cyclodehydration precedes nucleophile incorporation in a cyclodehydrative-nucleophilic-trapping (CNT) sequence, involving a reactive allyl cation intermediate. The substrate scope and preferred cyclization pathway (NAC or CNT) has been studied with respect to 3-aryl-2-carboxypropenone and the nature of the nucleophile. Also, for 1,3-diaryl-2-carboxypropenones, which can also undergo Nazarov cyclization, delineation between competing Nazarov and CNT pathways is controlled by the nature of the acid catalyst.
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