Acid-Catalyzed Ring-Opening Isomerizations of Cyclopropenes

Abstract

Acid-catalyzed cyclopropene cycloisomerizations are discussed as a means to generate ring systems. Herein, the recent results obtained in our group are contrasted with previous examples in the literature. Particular emphasis is placed on the mode of activation which, for our case, results in a different ring-opening mechanism than previously observed. The potential of the method as a tool for organic chemists is demonstrated by the synthesis of a host of benzo-fused heteroaromatic and heterobiaryl products.Cyclopropenes are highly strained carbocycles that have a range of reactivity beyond that of olefins, allenes, and alkynes. 1 While the presence of the double bond allows cyclopropenes to engage in addition reactions, liberation of the inherent ring strain enables cyclopropenes to undergo interesting ring-opening transformations. Cyclopropene cycloisomerizations represent one major class of these transformations that has garnered a tremendous amount of attention from synthetic chemists. 2 These reactions have been used as powerful synthetic tools due to their ability to construct carbo-and heterocyclic scaffolds with a high degree of molecular complexity and atom-economy. They have historically been promoted under thermal or photochemical conditions, however, over the past 50 years, cycloisomerizations promoted by transition metals have dominated the literature. 3 This is due to the fact that cyclopropenes have greater π-density than standard olefins, making them particularly attractive to π-philic transition metals. 4 For example, furans and pyrroles can be accessed from cycloisomerizations of 3-acyl-and 3-alkoxycarbonylcyclopropenes and cyclopropenyl imines using either Rh(II) or Cu(I) catalysts to generate metallocarbene species. 5 In contrast, few examples of protic or Lewis acid catalyzed cycloisomerizations have been documented in the literature. Herein, we discuss our contributions to this area within the greater and historical context of Brønsted and Lewis acid promoted cyclopropene ring-opening isomerizations. Historical examples are presented with particular emphasis on mechanistic details and insight.The earliest example of acid-mediated cyclopropene isomerization was reported in 1961 during the polymerization of sterculic acid (1, Scheme 1). 6 Heating sterculic acid in glacial acetic acid resulted in a complex mixture of four unsaturated allylic acetates. The purported mechanism involves protonation of the cyclopropene at either end of the π-system to generate the regioisomeric cyclopropyl cations 2 and 3. Ring-opening rearrangement then provides the pair of allylic cations 4 and 5, respectively. Acetic acid trapping at either end of both systems affords the four observed allylic acetates 6a-d.As part of their interest in the rearrangements of cyclopropyl cations, Breslow and co-workers demonstrated two examples of acid-promoted cyclopropene isomerizations. 7 In the first instance, diphenylcrotonolactone (8) was obtained when diphenylcyclopropene carboxylic acid 7 was treated with a protic acid (Sch...