21cycloaddition

21cycloaddition, commonly denoted [2+1] cycloaddition, refers to a class of cycloaddition reactions in which a two-electron fragment such as an alkene or alkyne reacts with a one-atom species bearing a pair of electrons to form a three-membered ring, usually a cyclopropane. The prototypical example is cyclopropanation of alkenes by carbenes or nitrenes, generated from diazo compounds or azides, respectively.

Mechanism and stereochemistry: the reaction can proceed concertedly with singlet carbenes, leading to stereospecific transfer of the alkene geometry to the cyclopropane; or stepwise via diradical or zwitterionic pathways with triplet carbenes, which can erode stereoselectivity. The outcome is influenced by substituents, solvent, and the energy of the involved fragments.

Catalysis and scope: transition-metal catalysts such as rhodium, copper, or iron complexes with chiral ligands enable enantioselective cyclopropanations of a wide range of alkenes. Carbenes are typically generated from diazo compounds; nitrenes from azides or related precursors. Intramolecular variants exist and can deliver fused or spirocyclopropanes.

Applications: 21cycloaddition provides a practical route to cyclopropane rings found in natural products, pharmaceuticals, and functional materials. It also serves as a versatile handle for further transformations, including ring-opening and functionalization.

Safety and limitations: diazo compounds and azides are potentially hazardous; reactions require appropriate setup and handling. Competing pathways include carbene dimerization or insertion into C–H bonds, making catalyst choice and reaction design important.