Enone Olefin [2 + 2] Photochemical Cycloadditions

Crimmins, Michael T.; Reinhold, Tracy L.


The photochemical [2 + 2] cycloaddition reaction of alkenes to enones, the light-induced cycloaddition of an excited state enone to a ground state alkene to produce a cyclobutane, is a highly useful reaction in organic synthesis since two new carbon–carbon bonds are formed and a maximum of four new stereogenic centers are introduced into the molecule in the process. The first [2 + 2] photocycloaddition reaction was reported by Ciamician in 1908 when he observed the formation of carvone camphor on exposure of carvone to sunlight for one year.

After confirmation of this finding in the late 1950s numerous investigators immediately recognized the value of the reaction for the rapid construction of complex molecular frameworks. The photocycloaddition of a series of Diels–Alder adducts of various dienes and benzoquinones to efficiently produce complex caged structures was subsequently carried out. This included the cycloaddition of a diketone to form a diketone. Meanwhile, a similar photochemical cycloaddition of an enone was utilized in a synthesis of the platonic solid cubane. Shortly thereafter investigations of the intermolecular reaction were initiated through a study of the dimerization of cyclopentenone and the photocycloaddition of cyclopentenone to cyclopentene.

Further investigation of the various synthetic and mechanistic aspects of the photocycloaddition resulted in several total syntheses, including caryophyllene and bourbonene, as well as a proposed mechanistic rationale for the reaction. As a result of this pioneering work, largely by Eaton, Corey, and De Mayo, numerous natural and nonnatural products have been prepared by synthetic routes which have a [2 + 2] photocycloaddition as a crucial step in their synthesis. Through further refining over the last 15–20 years, the photocycloaddition reaction has become recognized as an important transformation in the repertoire of the synthetic organic chemist.

Both the intermolecular and intramolecular versions of the reaction have been extensively studied. The intramolecular photocycloaddition, like the intramolecular variation of many reactions, has been the subject of much recent work. It is generally thought to be more predictable with regard to regiochemical and stereochemical control, but as will be seen from many of the examples in this chapter, the intermolecular reaction can be highly selective and predictable if the proper reaction participants and conditions are chosen.

This chapter reviews the literature on the enone olefin [2 + 2] photocycloaddition since its discovery. Because of the volume of work in the field, there will undoubtedly be some omissions. Examples of all the major types of enone alkene photocycloadditions have been included so that the reader can get a sense of the historical evolution and the current state of the art. Both the intermolecular and the intramolecular variants of this reaction are treated in this chapter. The reader is also referred to a number of excellent reviews on the intermolecular reaction, the intramolecular reaction, and complete treatments which have appeared.