[2+2] Photocycloaddition of Cinnamates in Flow and Development of a Thiourea Catalyst

Abstract

Cyclobutanes derived from the dimerization of cinnamic acids are the core scaffolds of many molecules with potentially interesting biological activities. By utilizing a powerful flow photochemistry platform developed in our laboratory, we have evaluated the effects of flow on the dimerization of a range of cinnamate substrates. During the course of the study we also identified a bis(thiourea) catalyst that facilitates better reactivity and moderate diastereoselectivity in the reaction. Overall, we show that carrying out the reaction in flow in the presence of the catalyst affords consistent formation of predictable cyclobutane diastereomers.

Studies in organic and physical photochemistry – an interdisciplinary approach

“…In when it is carried out in a continuous flow reactor. 106 In this case, the reactivity is increased by two hydrogen bonds between thiourea compound and the carboxyl group of the cinnamate. …”

Towards More Efficient, Greener Syntheses through Flow Chemistry

“…Scaling this type of reaction in flow can easily be achieved by running parallel reactors, or, if time permits, simply increasing the duration of the product collection period. While in‐house reactors such as the one shown in Figure a can be readily fashioned for UV, LED, and visible light, flow photoboxes are also commercially available (Figure b and 5c) …”

Templating and Catalyzing [2+2] Photocycloaddition in Solution Using a Dynamic G‐Quadruplex

“…Molecular containers can facilitate [2+ +2] photocycloaddition of alkenes,o ften with good regio-and stereoselectivity. [19,20] Our goal was to use aG-quadruplex, arobust H-bonded assembly, as as upramolecular template to orient multiple cinnamates for photodimerization in dilute solution. Sometimes, these reactions are catalytic as cyclobutane product exchanges with reactants,e nabling turnover.…”

“…[17] Intermolecular H-bonding of 2a lkenes to at emplate can also trigger [2+ +2] cycloaddition of cinnamate esters in solution, [18,19] and some of these H-bonding templates act as catalysts. [19,20] Our goal was to use aG-quadruplex, arobust H-bonded assembly, as as upramolecular template to orient multiple cinnamates for photodimerization in dilute solution.…”