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Bifunctional Amine-Squaramides as Organocatalysts in Michael/hemiketalization Reactions of β,γ-Unsaturated α-Ketoesters and α,β-Unsaturated ketones with 4-Hydroxycoumarins.

Research paper by Viktoria V Modrocka, Eva E Veverkova, Maria M Meciarova, Radovan R Sebesta

Indexed on: 03 Oct '18Published on: 03 Oct '18Published in: Journal of Organic Chemistry



Abstract

The catalytic efficiency of various amine-squaramides has been tested in Michael/hemiketalization reactions of 4-hydroxycoumarines with two types of enones. Tertiary amine-squaramide organocatalysts afforded the best results regarding both activity and enantioselectivity when β,γ-unsaturated α-ketoesters were used as the Michael acceptors (yields up to 98%, enantioselectivities up to 90% ee). On the other hand, the primary amine-squaramides are the best choice for related reactions of 4-hydroxycoumarins with enones. The corresponding pyrano[3,2-c]chromen-5-on products were obtained in high enantiomeric purities (up to 96%). The Michael addition of 4-hydroxycoumarin to 4-phenylbut-3-en-2-on directly produced chiral anticoagulant drug (S)-warfarin in 92% ee, when green solvent 2-MeTHF and catalyst (S,S)-C8 was used. Moreover, an enantiomeric catalyst (R,R)-C8 gave (R)-warfarin in >99 % ee.