Synthesis of Azetidines based on Visible-light Photocatalytic [2+2] Aza Cycloaddition Between Alkenes and Imines

다국어 초록 (Multilingual Abstract)

The organic compounds which have four-membered ring structure are fascinating in organic chemistry, since they have been found in numerous bioactive molecules and used as useful synthon due to their ring strain. Among them, the azetidine which is nitrogen-containing four-membered heterocycle starts to gain in popularity as an interesting pharmacophore in current medicinal chemistry because of their desirable biological activity and improved metabolic stability. Also, as a synthon, their strained structure makes them excellent candidates for ring expansion reactions. In spite of their strong points, the lack of efficient synthetic method of azetidine is still remaining challenge.
Among the known synthetic strategies, the [2+2] photocycloaddition reaction between imine and alkene has emerged as prominent method, which can directly afford the functionalized azetidine. However, because of low reactivity between imines and alkenes, previous methods usually relied on UV irradiation in order to activate the imine or alkene. UV irradiation can excite both alkene and imine so that the C=N bond can undergo undesired relaxation pathways such as isomerization, fragmentation, or decomposition. Some research groups designed rigid imine and alkene substrates to solve that, but still UV light is hazardous, and it has limited the functional groups of substrates.
To break through these drawbacks, we developed the visible light induced photocatalytic [2+2] cycloaddition reaction between imine and alkene. The selective activation of alkene was achieved via redox mechanism to avoid the excitation of imine or other functional groups. Using blue LED as light source and acridinium catalyst as organophotocatalyst, a variety of azetidine compounds were synthesized in moderate to excellent yield without any by-product.
This redox neutral method gives product only and utilizes acridinium photocatalyst which is eco-friendly, cheap, and less toxic than metal photocatalysts. Therefore, it allows a highly atom economic reaction and it is highly desirable in green chemistry. Also, the constructed bicyclic azetidine moiety have great potential in biological activity and further modification.