Cyclopropene Chemistry and Catalytic Synthesis

Cyclopropenes, the smallest isolable unsaturated carbocycles, combine pronounced ring-strain with a reactive π-bond to enable diverse transformations under mild conditions. Their distinctive reactivity has been harnessed in cyclopropanation, nucleophilic substitution, ring-opening and benzannulation processes, often mediated by transition-metal catalysts. Catalytic approaches using iron, nickel, cobalt, rhodium and gold complexes deliver high levels of regio-, diastereo- and enantioselectivity, granting access to complex heterocycles, polysubstituted scaffolds and aromatic frameworks. Mechanistic insights from combined experimental studies and density functional theory underpin catalyst design and stereocontrol strategies. The versatility of cyclopropene chemistry has found broad applications in pharmaceutical and agrochemical synthesis, late-stage functionalisation of bioactive molecules and the assembly of advanced materials, highlighting both academic appeal and industrial relevance.

Research from Nature Portfolio

Researchers have demonstrated that a simple, environmentally benign iron(III) catalyst can directly promote intramolecular substitution of enantiomerically enriched secondary and tertiary alcohols, converting them into five- and six-membered heterocycles with complete retention of stereochemical integrity. Water is the sole by-product, underlining the sustainability of the protocol and its utility in total synthesis endeavours.

Recent developments in nickel catalysis have enabled a cyclopropene–isocyanide [5+1] benzannulation. An N-heterocyclic carbene–Ni(II) complex orchestrates the direct addition of unactivated cyclopropenes to isocyanides, delivering functionalised anilines and spirocyclic aromatic amines. The broad substrate scope, supportive crystal structures and cooperative steric and electronic control illustrate a powerful route to aromatic nitrogen compounds.

Cyclopropene Chemistry and Catalytic Synthesis publication trend

The graph below shows the total number of articles in cyclopropene chemistry and catalytic synthesis across all publications each year (not limited to Nature Index journals).

Technical terms

Cyclopropene: A three-membered unsaturated carbocycle featuring a strained double bond, prone to ring opening and catalytic transformations.

Cyclopropanation: A reaction that forms a cyclopropane ring by insertion of a carbene equivalent into an alkene or alkyne substrate.

Benzannulation: A process by which non-aromatic precursors are converted into aromatic ring systems, often via metal-catalysed insertion reactions.

Carbometalation: The addition of an organometallic reagent across a multiple bond, generating a new carbon–metal bond and a carbon–carbon bond in a single step.

Stereocentre: An atom at which the interchange of two groups produces a stereoisomer, critical for defining three-dimensional molecular geometry and biological activity.

References

1. Ring Transformation of Cyclopropenes to Benzo‐Fused Five‐Membered Oxa‐ and Aza‐Heterocycles via a Formal [4+1] Cyclization. Advanced Science (2024).
2. Intramolecular substitutions of secondary and tertiary alcohols with chirality transfer by an iron(III) catalyst. Nature Communications (2019).
3. Stereoselective Synthesis of Polysubstituted Spiropentanes. Journal of the American Chemical Society (2022).
4. NHC-Ni(II)-catalyzed cyclopropene-isocyanide [5 + 1] benzannulation. Nature Communications (2022).