Cyclopropenone Chemistry and Synthetic Transformations

Cyclopropenones represent the smallest isolable cyclic ketones, distinguished by a three-membered ring that merges substantial ring strain with conjugated carbonyl character. This unusual combination endows cyclopropenones with dual reactivity profiles: as electrophilic ketones susceptible to nucleophilic attack and as strained scaffolds poised for ring-opening C–C bond activation. Over the past decade, advances in catalysis have harnessed these features to construct complex heterocycles, enable enantioselective bond formation and develop photochemical routes to functionalised cyclopropenone derivatives. Synthetic transformations now range from metal-mediated ring expansions and annulations to organocatalytic additions, yielding diverse scaffolds of interest in medicinal chemistry and materials science. The ability to tune electronic and steric properties through substitution on the cyclopropene core further amplifies its value as a versatile building block for drug leads, agrochemicals and polycyclic frameworks.

Research from Nature Portfolio

Recent studies have demonstrated palladium-catalysed ring-opening of substituted cyclopropenones to afford densely functionalised conjugated dienones under mild conditions, enabling sequential cross-coupling and cascade cyclisations that furnish complex carbocyclic motifs with exceptional regio- and stereocontrol. Complementary work has showcased enantioselective activation of cyclopropenones via chiral nickel complexes, wherein asymmetric C–C bond cleavage is followed by intramolecular trapping to generate chiral γ-lactones and spirocyclic architectures in high enantiomeric excess. A further highlight is the development of a photocatalytic approach that converts simple alkenes to cyclopropenone derivatives through visible-light-induced carbenoid insertion, providing a streamlined entry to substituted rings without the need for pre-formed diazo precursors. Collectively, these reports underscore the maturation of cyclopropenone chemistry into a toolkit for precision synthesis of structurally elaborate targets.

Cyclopropenone Chemistry and Synthetic Transformations publication trend

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

Technical terms

Cyclopropenone: A three-membered cyclic ketone with conjugated π-system and high ring strain, combining electrophilic carbonyl reactivity with C–C bond activation potential.

Ring strain: The destabilisation energy arising from bond angles deviating significantly from the ideal values of sp² or sp³ hybridised carbons.

C–C bond activation: The cleavage of a carbon–carbon bond under catalytic or photochemical conditions to permit skeletal rearrangements or functionalisation.

Annulation: A ring-forming reaction that constructs one or more rings onto a molecular scaffold, often via cycloaddition or cascade processes.

Enantioselectivity: The preferential formation of one enantiomer over another in a chemical reaction, typically quantified by enantiomeric excess.

References

1. Novel quinoline/thiazinan-4-one hybrids; design, synthesis, and molecular docking studies as potential anti-bacterial candidates against MRSA. RSC Advances (2023).
2. Rhodium(III)-Catalyzed Redox-Neutral [3+3] Annulation of N-nitrosoanilines with Cyclopropenones: A Traceless Approach to Quinolin-4(1H)-One Scaffolds. Molecules (2020).
3. Reaction of diphenylcyclopropenone with N-acylamidine derivatives. Synthetic and mechanistic implications. Journal of the Brazilian Chemical Society (2001).