Gold-Catalyzed Tandem Reactions of Methylenecyclopropanes and Vinylidenecyclopropanes

Abstract

Gold catalysis is often the key step in the synthesis of natural products, and is a powerful tool for tandem or domino reaction processes. Both gold salts and complexes are among the most powerful soft Lewis acids for electrophilic activation of carbon-carbon multiple bonds toward a variety of nucleophiles. The core of these reactions relies on the interaction between gold catalysts and π-bonds of alkenes, alkynes, and allenes. Activation of functional groups by gold complexes provides a useful and important method for facilitating many different organic transformations with high atom efficiency. Although they are highly strained, methylenecyclopropanes (MCPs) and vinylidenecyclopropanes (VDCPs) are readily accessible molecules that have served as useful building blocks in organic synthesis. Because of their unique structural and electronic properties, significant developments have been made in the presence of transition metal catalysts such as nickel, rhodium, palladium, and ruthenium during the past decades. However, less attention has been paid to the gold-catalyzed chemistry of MCPs and VDCPs. In this Account, we describe gold-catalyzed chemical transformations of MCPs and VDCPs developed both in our laboratory and by other researchers. Chemists have demonstrated that MCPs and VDCPs have amphiphilic properties. When MCPs or VDCPs are activated by a gold catalyst, subsequent nucleophilic attack by other reagents or ring-opening (ring-expansion) of the cyclopropane moiety will occur. However, the C-C double bonds of MCPs and VDCPs can also serve as nucleophilic reagents while more electrophilic reagents are present and activated by gold catalyst, and then further cascade reactions take place as triggered by the release of ring strain of cyclopropane. Based on this strategy, both our group and others have found some interesting gold-catalyzed transformations in recent years. These transformations of MCPs and VDCPs can produce a variety of polycyclic and heterocyclic structures, containing different sized skeletons. Moreover, we have carried out some isotopic labeling experiments and computational studies for mechanistic investigation. These reactions always give the desired products with high level control of chemo-, regio-, and diastereoselectivities, making them highly valuable for the synthesis of natural products and to the pharmaceutical industry and medicine in general.

Synthesis of Functionalized Alkylidenecyclopropanes by Ireland–Claisen Rearrangement of Cyclopropenylcarbinyl Esters

“…5 Among the different synthetic routes toward alkylidenecyclopropanes, transformations relying on cyclopropenes as precursors are thermodynamically favored owing to the relief of ring strain occurring upon migration of the double bond to the exocyclic position. 1,6 Nucleophilic displacements of cyclopropenylcarbinol derivatives proceeding with allylic shift (S N 2′ or addition−elimination mechanisms) are undoubtedly the most documented transformations. 7 Surprisingly, by analogy with allylic alcohols, examples of [3,3]-sigmatropic rearrangements involving cyclopropenylcarbinol derivatives are scarce and restricted to the synthesis of heterosubstituted alkylidenecyclopropanes.…”

Present and Future of Cyclopropanations in Fragrance Chemistry

“…cycloisomerization reactions seem to hold even more promises ahead [47] and the thusobtained products have at least the right molecular weight (150 -250 Dalton) and often the right functionality (alcohols, ketones) to be volatile and recognized by olfactory receptors. The same is true for metal-catalyzed ring-expansion reactions of vinyl-or alkynyl-cyclopropanes as well as methylene-or allene-cyclopropanes [48].…”

The Construction of Molecular Complexity from Functionalized Alkylidenecyclopropanes (FACPs)

“…During our continuous investigation of gold‐catalyzed reactions of FACPs, we conclude that a proximal bond (C2−C3 or C2−C4) cleavage occurs in most cases, whereas a distal bond (C3−C4) cleavage is rarely reported (Scheme a) . Recently, we reported an unusual gold‐catalyzed distal bond cleavage of the FACPs 32 to prepare functionalized 11 H ‐benzo[ a ]fluorine derivatives through exclusive cleavage of the distal C−C bond of alkylidenecyclopropanes.…”