Application of the [4+4] photocycloaddition is scarce because of competition with the [[2+2 Photocycloaddition|[2+2] cycloaddition]]. However, when accessible, this method can be used to build 8-membered ring with complex stereocenters and structures in one step, as is seen in proposed syntheses for Taxol and molecules of the fusicoccin family. Additionally, while this reaction first forms fused rings, subsequent cleavages can afford macrocycles.
In this partial synthesis of the BC rings of Taxol, the framework buildup utilized an intramolecule [4+4] photocycloaddition of a relatively linear and simple 2-pyridone derivative, folding it into the desired fused rings with correct stereochemistry at C3, C8, and C15 (compare with Taxol on the right) and two double bonds on the B ring ready to accept trans-addition. Consequent lactam-ring opening and functionalization were expected to give Taxol.
Similarly, molecules of the fusicoccin family, featuring 5-8-5 ring systems, could be constructed rapidly using this reaction. Although the high stereoselectivity of this reaction to form trans-isomers made it unsuitable for the specific target molecules, the general ease to create the four tertiary chiral centers is still noteworthy.
Use of [4+4] photocycloaddition need not be limited to the creation of 8-membered rings. By linking up a network of rings and then breaking the shared bonds, a single macrocycle with built-in stereocenters could be achieved.