A Combination of Visible-Light Organophotoredox Catalysis and Asymmetric Organocatalysis for the Enantioselective Mannich Reaction of Dihydroquinoxalinones with Ketones

Abstract

An enantioselective photooxidative Mannich reaction of dihydroquinoxalinones with ketones by the merger of organophotoredox and asymmetric organocatalysis is described. This protocol features a very mild reaction conditions using simple and cheap catalysts (Eosin Y and (S)-Proline) for the synthesis of chiral quinoxaline derivatives with good to high yields (up to 94%) and excellent enantioselectivities (up to 99% ee).

Recent Advances in Photocatalytic Functionalization of Quinoxalin‐2‐ones

“…In 2019, our research group developed a one-pot methodology for the enantioselective Mannich reaction between 3,4-dihydroquinoxalin-2-ones and ketones by combining organophotoredox catalysis and organocatalysis. [85] After the optimization process, we realized that Eosin Y-Na 2 and (S)-Proline were the best photocatalyst and organocatalyst, respectively. Using this couple of catalysts, along with DMF as solvent, we could prepare twenty-two differently substituted 3,4-dihydroquinoxalin-2-ones with several ketones in good to high yields and excellent enantioselectivities (up to 99 % ee) (Scheme 68).…”

Recent Advances in Asymmetric Organomulticatalysis

“…Recently, Vila and coworkers reported an enantioselective Mannich reaction to generate chiral quinoxaline derivatives 184 using a combination of visible‐light organophotoredox catalyst (eosin Y) and chiral amino acid D ‐proline (Scheme 55). [96] With this strategy, not only is the electrophile 185 formed in situ through cooperative catalysis, it is also subsequently consumed by utilizing the same combination catalysis. Overall, the two step sequence involves the oxidation of dihydroquinoxalinones 182 to generate the cyclic imine 185 , along with the formation of enamines Int‐137 via enamination of S ‐proline and ketones 183 .…”

Asymmetric Oxidative Mannich Reactions

“…In 2019, our research group developed a dual catalytic protocol to functionalize, enantioselectively, the C‐3 position of 3,4‐dihydroquinoxalin‐2‐ones with ketones using as organocatalyst ( S )‐proline [56] . The structural motif of 3,4‐dihydroquinoxalin‐2‐one is present in several molecules with biological activity and therefore have attracted the attention of the synthetic chemistry community [57] .…”