Monash Institute of Pharmaceutical Sciences , Monash University , 381 Royal Parade , Parkville 3052 , Victoria , Australia.
J Org Chem. 2019 Mar 1;84(5):2756-2767. doi: 10.1021/acs.joc.8b03042. Epub 2019 Feb 12.
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.
易于获得的 3-芳基-2-羧基丙烯酮（通过 Knoevenagel 缩合反应）在酸促进下进行环脱水反应，并与亲核试剂结合，形成高度取代的茚。对于更强的亲核试剂，亲核试剂的结合发生在环脱水反应之前，这是一个亲核加成-环脱水（NAC）序列。对于较弱的亲核试剂，环脱水反应先于亲核试剂的结合，这是一个环脱水-亲核捕获（CNT）序列，涉及到一个反应性烯丙基阳离子中间体。已经研究了 3-芳基-2-羧基丙烯酮和亲核试剂的性质对底物范围和首选环化途径（NAC 或 CNT）的影响。此外，对于 1,3-二芳基-2-羧基丙烯酮，其也可以发生 Nazarov 环化反应，酸催化剂的性质控制着竞争的 Nazarov 和 CNT 途径之间的划分。
