The optimal conditions for TMM cycloadditions depend on both the TMM source and two-atom component. However, a few general principles for each of the TMM sources have emerged.
Reactions of diazenes should employ degassed solvents to avoid radical reactions with oxygen. Tetrahydrofuran (THF) at reflux is the most commonly employed solvent system, but photodissociation conditions at low temperature may also be used.
Reactions employing polar MCPs are usually carried out in a polar solvent to facilitate formation of the TMM intermediate. Although rigorous exclusion of air and water is not required, it is generally preferred.
For transition-metal catalyzed MCP reactions, the choice of catalyst and ligand system is key. Generally, phosphine or phosphite ligands are required in conjunction with a palladium(0) or nickel(0) source; the most common are Pd(dba) and Ni(cod). Tri(isopropyl)phosphine is the most common ligand used with palladium, and triarylphosphites are usually added in nickel-catalyzed reactions.
For transition-metal catalyzed reactions of silylated allylic acetates, the most commonly used catalyst system is palladium(II) acetate and tri(isopropyl)phosphite. Reactions are usually carried out in THF at temperatures ranging from 60 to 110 °C. The choice of solvent or leaving group may affect the course of the reaction.