The substitution of CO ligands can be induced thermally or photochemically by donor ligands. The range of ligands is large, and includes phosphines, cyanide (CN), nitrogen donors, and even ethers, especially chelating ones. Alkenes, especially dienes, are effective ligands that afford synthetically useful derivatives. Substitution of 18-electron complexes generally follows a dissociative mechanism, involving 16-electron intermediates.
Substitution proceeds via a dissociative mechanism:
:M(CO) → M(CO) + CO
:M(CO) + L → M(CO)L
The dissociation energy is  for nickel tetracarbonyl and  for chromium hexacarbonyl.
Substitution in 17-electron complexes, which are rare, proceeds via associative mechanisms with a 19-electron intermediates.
:M(CO) + L → M(CO)L
:M(CO)L → M(CO)L + CO
The rate of substitution in 18-electron complexes is sometimes catalysed by catalytic amounts of oxidants, via electron transfer.