Hydroaminoalkyl Functionalization of Pyrimidin-2(1H)-ones by Visible Light Organophotocatalysis: A Radical Approach to Biginelli-Type Dihydropyrimidines

Herein, we report a visible-light-mediated hydroaminoalkylation of pyrimidin-2(1H)-ones via the aza-Giese-type reaction in presence of acridinium dye as photocatalyst under mild aerobic conditions. Using N-Boc protected aminoalkyl trifluoroborates as radical precursors and various pyrimidine-2(1H)-one substrates, a diverse set of Biginelli-type 3,4-dihydropyrimidin-2(1H)-ones was prepared in 31-73% yields. Further transformation of the products obtained enabled the synthesis of 3,6,7,7a-tetrahydro-1H-pyrrolo[3,4d]pyrimidine-2,5-dione derivatives which showed promise as inhibitors of poly (ADP-ribose) polymerase (PARP) enzymes (IC50 0.46-1.12 mu M for PARP-2 in a fluorometric assay).