[2+2] Photochemical Cycloaddition in Organic Synthesis

Abstract

The century old [2+2] photocycloaddition reaction appeared as the most synthetically useful reaction amongst all photochemical reactions. It provides not only cyclobutane ring systems, but at the same time it provides access to medium rings through facile ring expansion/fragmentation of the strained cyclobutane ring. The high regio‐and stereoselectivity observed during cycloaddition has made it an attractive tool for synthesis of multicyclic structurally complex natural products. The vast majority of [2+2] photocycloaddition reactions involves enone–alkene cycloaddition which is conveniently achieved through direct excitation or sensitization by UV irradiation. Substantial progress has also been made in [2+2] cycloaddition between two unactivated alkenes using transition metal salts especially copper(I) salts. Sometimes Cu(I)‐catalyzed cycloaddition is advantageous over enone–alkene photocycloaddition. Search for an alternative source to environmentally harmful high energy UV light has led to the discovery of transition metal salts which can be used to excite alkenes by visible light. This causes alkenes to undergo [2+2] cycloaddition and has been used for synthesis of cyclobutane derivatives. This review aims to give an overview about different aspects of [2+2] photocycloaddition reaction with an emphasis in the stereoselective synthesis of selected complex natural products and related molecules where cycloaddition has been used as the key step.

Synthesis of azetidines by aza Paternò–Büchi reactions

“…As a result, there exist numerous examples in the literature, in which [2 + 2] photocycloaddition reactions have been used for the synthesis of complex natural products. 2 The most commonly employed type is the photocycloaddition between two alkene components to afford cyclobutanes, in which upon excitation of one of the reaction partners two new carbon–carbon bonds are formed. 3 Similarly, excitation of a carbonyl compound in the presence of an alkene can result in a [2 + 2] photocycloaddition reaction to provide an oxetane as product, known as the Paternò–Büchi reaction.…”

Novel Symmetrical Cage Compounds as Inhibitors of the Symmetrical MRP4-Efflux Pump for Anticancer Therapy

“…As a reduced pyridine the 1,4-dihydropyridine scaffold owns two neighbored double bonds. A double bond may undergo a [2+2] cycloaddition reaction with another double bond to form cyclobutane compounds after irradiation with light under double bond excitation [ 20 ]. Pyrone compounds are known to form photodimers by the reaction of neighbored double bonds under UV light irradiation as cage compounds with resulting neighborhood cyclobutane rings that form the cage compound walls [ 21 ].…”

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

“…In addition [2 + 2] cycloadditions have also been of great interest in organic synthesis as cyclobutanes are key intermediates for the preparation of larger rings (via ring expansion) as well as enabling formation of interesting 4-membered rings such as lactam and lactones [ 492 – 493 ]. The [2 + 2] cycloadditions involve an olefin at its singlet/triplet excited state (SOMO) and a alkene at its ground state (LUMO) [ 494 ].…”