Recent Advances in Transition-Metal-Catalyzed/Mediated Transformations of Vinylidenecyclopropanes

Abstract

Vinylidenecyclopropanes (VDCPs), having an allene moiety connected to a highly strained cyclopropyl group, have attracted a substantial amount of attention since they are fascinating building blocks for organic synthesis. During recent years, the reactions of VDCPs in the presence of a Lewis acid or a Brønsted acid and those induced by heat or light have experienced significant advancements due to the unique structural and electronic properties of VDCPs. Transition-metal-catalyzed reactions of VDCPs were not intensely investigated until the last 5 years. Recently, significant progress has been made in transition-metal-catalyzed transformations of VDCPs, and they have emerged as a new direction for the chemistry of strained small rings, especially when new types of functionalized vinylidenecyclopropanes (FVDCPs) are used as substrates. To date, many interesting transformations have been explored using these novel VDCPs under the catalysis of transition metals, such as gold, palladium, or rhodium, and various novel and useful heterocyclic or polycyclic compounds have been generated. These new findings have enriched the chemistry of strained small carbocycles. This Account will describe the transition-metal-catalyzed transformations of VDCPs recently developed in our laboratory and by other groups. The chemistry of Au-catalyzed VDCPs has been enriched and extensively developed by our group. In this respect, a new process for generating gold carbenes from VDCPs has been disclosed. The reactivity of these new gold carbenoid species was fully investigated, and many novel reaction modes based on these new gold carbenoid species were explored, including oxidation reactions, intramolecular cyclopropanations, C(sp)-H bond functionalizations, and C-O bond cleavage reactions. Rh-catalyzed reactions of VDCPs are another key field of transition-metal-catalyzed reactions of VDCPs. In particular, rhodium-catalyzed cycloadditions, Pauson-Khand reactions, and C-H bond activations of FVDCPs have been explored in detail by our group. A new trimethylenemethane rhodium (TMM-Rh) complex generated from VDCPs was discovered and utilized as an electrophilic Rh-π-allyl precursor. Moreover, some unprecedented highly regio- and enantioselective asymmetric allylic substitutions via this novel TMM-Rh complex were developed with different kinds of nucleophiles. This Account will also summarize the recent advances in palladium-, copper-, and iron-catalyzed cycloisomerization reactions of VDCPs reported by our group and others. These reactions always afford the desired products with excellent chemo-, regio-, diastereo-, and enantioselectivities, which will make them highly valuable for the synthesis of key scaffolds in natural products and pharmaceutical molecules in the future.

Carbolong Chemistry: Planar CCCCX-Type (X = N, O, S) Pentadentate Chelates by Formal [3+1] Cycloadditions of Metalla-Azirines with Terminal Alkynes

“…Nucleophilic addition of the nitrogen atom in the metalla-azirine ring to the α-carbon atom of the metal-vinylidene would lead to the formation of a four-membered aza-metallacyclobutene. At this point, the coordination geometry at the metal allows the pyridyl to coordinate with the metal center, affording the tethered five-membered metallacycle that is an important contributor to the final tetracyclic complex (5). Our density functional theory (DFT) calculations support the mechanisms and reveal that the formal [3+1] cycloaddition process from B to 5 is indeed exergonic.…”

“…Ring-expansion reactions of compounds with small rings are one of the fundamental transformations in organic synthesis. [1][2][3][4][5][6] Among the various strained rings, three-membered unsaturated rings are common and can serve as three-atom synthons in a variety of addition reactions taking advantage of their high reactivity, which is derived from ring strain. 4,6 With the exception of certain synthetic equivalents or analogues, [7][8][9][10][11][12] however, previously reported addition reactions of alkynes to these three-membered unsaturated rings were seen as ring-expansion transformations, typically following a [3+2] cycloaddition pathway.…”

Gold-Catalyzed Conversion of Highly Strained Compounds

“…Recently, transition metal-catalyzed, and in particular gold-catalyzed, transformations of VDCPs have made significant progress. A multitude of novel transformations have been disclosed where VDCP substrates are converted under gold catalysis to various novel and useful heterocyclic or polycyclic compounds …”

Catalytic Enantioselective Ring-Opening Reactions of Cyclopropanes

“…Vinylidenecyclopropanes (VDCPs) are a class of three-membered ring carbocycles bearing an allene group, resulting in a high strain energy (51 kcal mol –1 ) . With appropriate substituents, VDCPs are stable and were shown to be suitable substrates for enantioselective ring-opening transformations . Only a few examples of asymmetric catalysis have been reported so far by the group of Shi, including C­(sp 3 )–H functionalizations, hydrofunctionalizations, cycloisomerizations, and annulations.…”

“…Finally, the last three sections will discuss special classes of cyclopropanes substituted with C–C unsaturations: Vinylcyclopropanes (section ), alkylidenecyclopropanes (section ), and vinylidenecyclopropanes (section ). The presence of the more reactive π systems opens the way for other types of transition-metal-based activations, which has been described in dedicated reviews, − none of them specific to asymmetric transformations however. Cyclopropenes have been only rarely used in asymmetric ring-opening transformations and are not covered in this review …”