Visible-Light-Driven [2 + 2] Photocycloaddition for Constructing Dimers of N,N′-Diacyl-1,4-dihydropyrazines: Experimental and Theoretical Investigation

Abstract

In this study, the visible-light-driven [2 + 2] photocycloaddition of 1,4-dihydropyrazines in solution was reported. The N,N′-diacyl-1,4-dihydropyrazines with different substituents showed completely different reactivity under the irradiation of a 430 nm blue light-emitting diode (LED) lamp. N,N′-Diacetyl-1,4-dihydropyrazine and N,N′-dipropionyl-1,4-dihydropyrazine were the only compounds capable of undergoing a [2 + 2] photocycloaddition reaction, yielding syn-dimers and cage-dimers (known as 3,6,9,12-tetraazatetraasteranes) with overall yields of 76 and 83%, correspondingly. The substituent-reactivity effect on [2 + 2] photocycloaddition of N,N′-diacyl-1,4-dihydropyrazines was investigated by density functional theory calculations. The results show that the substituents have little influence on Gibbs free energy for the [2 + 2] photocycloaddition and mainly affect the excited energy, reaction sites, and the triplet excited-state structures of 1,4-dihydropyrazines, which are closely related to whether the reaction occurs. The results offer insights into the photochemical reactivity of 1,4-dihydropyrazines and an approach for constructing dimers of N,N′-diacyl-1,4-dihydropyrazines through a solution-based visible-light-driven [2 + 2] photocycloaddition, especially for the construction of 3,6,9,12-tetraazatetraasteranes. Compared with the solid-state [2 + 2] photocycloaddition of 1,4-dihydropyrazine, this photocycloaddition will be an efficient and environmentally friendly method for synthesizing tetraazatetraasteranes with the advantages of milder reaction conditions, simple operation, adjustable reaction amounts by omitting the cocrystal growth step, etc.