Organocatalytic cascade nucleophilic/aza-Michael addition reactions: metal-free catalytic strategy for the synthesis of hydantoins

Abstract

Lewis base-catalyzed cascade nucleophilic/aza-Michael addition reaction of N-alkoxy β-oxo-acrylamides with isocyanates has been developed to afford various highly functionalized hydantoin derivatives in 80-98% yields under mild reaction conditions. The intriguing...

Synthesis of Polycyclic Imidazolidinones via Cascade [3 + 2]-Annulation of β-Oxo-acrylamides with Cyclic N-Sulfonyl Imines

“…In this context, acrylamides-involved cascade annulation reaction has been explored in great detail, in which acrylamide serves as a N , C β -1,4-synthon to undergo cascade [4 + 2]-annulation reactions with electron-deficient alkenes to construct δ-lactam scaffolds . Comparatively, β-electron-withdrawing group (ester or carbonyl)-tethered acrylamide usually acts as a N , C α -1,3-synthon in chiral amine-catalyzed asymmetric cascade aza-Michael/Michael reaction with α, β-unsaturated aldehydes, as well as Lewis base-catalyzed formal [3 + 2]-annulation reactions with nitro-heteroarenes or isocyanates . On the other hand, cyclic N -sulfonyl imines exhibit versatile reaction activity in organocatalytic, metal-catalyzed, or radical-mediated cycloaddition reactions, which provide straightforward, powerful, and atom-economical methods to a wide range of diverse pharmacologically sultam or sulfamidate-fused nitrogen-containing heterocycles .…”

“…18 Comparatively, βelectron-withdrawing group (ester or carbonyl)-tethered acrylamide usually acts as a N, C α -1,3-synthon in chiral amine-catalyzed asymmetric cascade aza-Michael/Michael reaction with α, β-unsaturated aldehydes, 19 as well as Lewis base-catalyzed formal [3 + 2]-annulation reactions with nitroheteroarenes 20 or isocyanates. 21 On the other hand, cyclic Nsulfonyl imines exhibit versatile reaction activity in organocatalytic, metal-catalyzed, or radical-mediated cycloaddition reactions, 22 which provide straightforward, powerful, and atom-economical methods to a wide range of diverse pharmacologically sultam or sulfamidate-fused nitrogen-containing heterocycles. 23 Based on our achievements in the field of heterocyclic chemistry involving N-alkoxy α-halohydroxamate 24 or acrylamide, 21 and in line with our continuous efforts in annulation reactions, we have successfully established an Et 3 N-catalyzed aza-Mannich reaction triggered cascade annulation reaction of β-oxo-acrylamides with cyclic N-sulfonyl imines, leading to the formation of highly functionalized sulfamide-fused imidazolidinone derivatives (Scheme 2f).…”

“…On the other hand, cyclic N -sulfonyl imines exhibit versatile reaction activity in organocatalytic, metal-catalyzed, or radical-mediated cycloaddition reactions, which provide straightforward, powerful, and atom-economical methods to a wide range of diverse pharmacologically sultam or sulfamidate-fused nitrogen-containing heterocycles . Based on our achievements in the field of heterocyclic chemistry involving N -alkoxy α-halohydroxamate or acrylamide, and in line with our continuous efforts in annulation reactions, we have successfully established an Et 3 N-catalyzed aza-Mannich reaction triggered cascade annulation reaction of β-oxo-acrylamides with cyclic N -sulfonyl imines, leading to the formation of highly functionalized sulfamide-fused imidazolidinone derivatives (Scheme f). Meanwhile, we also studied the asymmetric [3 + 2]-cycloaddition reaction using chiral bifunctional squaramide organocatalysts.…”

N-Benzyloxyacrylamides as Bisnucleophiles in an Organocatalyzed Domino aza-Michael/Morita-Baylis-Hillman Sequence

“…On reaction with cinnamaldehyde derivatives or cyclic enones, these custom [1,3]-N,Cα-dipolar acrylamides gave, after subsequent NaBH 4 reduction in MeOH of the aldehyde function, the desired densely functionalized γ-lactams 4 . In line with Hamada’s work, Sun’s team and Xie et al have developed two related organocatalytic variants for the synthesis of γ-lactams 5 and 6 , respectively.…”