Rapid generation of molecular complexity in the Lewis or Brønsted acid-mediated reactions of methylenecyclopropanes.

Although they are highly strained, methylenecyclopropanes (MCPs) are readily accessible molecules that have served as useful building blocks in organic synthesis. MCPs can undergo a variety of ring-opening reactions because the release of cyclopropyl ring strain (40 kcal/mol) can provide a thermodynamic driving force for reactions and the π-character of the bonds within the cyclopropane can afford the kinetic opportunity to initiate the ring-opening. Since the 1970s, the chemistry of MCPs has been widely explored in the presence of transition metal catalysts, but less attention had been paid to the Lewis or Brønsted acid mediated chemistry of MCPs. During the past decade, significant developments have also been made in the Lewis or Brønsted acid mediated reactions of MCPs. This Account describes chemistry developed in our laboratory and by other researchers. Lewis and Brønsted acids can be used as catalysts or reagents in the reactions of MCPs with a variety of substrates, and substituents on the terminal methylene or on the cyclopropyl ring of MCPs significantly affect the reaction pathways. During the past decade, we and other researchers have found interesting transformations based on this chemistry. These new reactions include the ring expansion of MCPs, cycloaddition reactions of MCPs with aldehydes and imines, cycloaddition reactions of MCPs with nitriles in the presence of strong Brønsted acid, radical reactions of MCPs with 1,3-dicarbonyl compounds, intramolecular Friedel-Crafts reactions of MCPs with arenes, acylation reactions of MCPs, and the reaction of MCPs with 1,1,3-triarylprop-2-yn-1-ols or their methyl ethers. These Lewis or Brønsted acid mediated reactions of MCPs can produce a variety of new compounds such as cyclobutanones, indenes, tetrahydrofurans, and tetrahydroquinolines. Finally, we have also carried out computational studies to explain the mechanism of the Brønsted acid mediated reactions of MCPs with acetonitrile.