Haloamines as Bifunctional Reagents for Oxidative Aminohalogenation of Maleimides

Abstract

An unprecedented copper-catalyzed oxidative aminohalogenation of electron-deficient maleimides with secondary amines and NXS (X = Cl, Br, I) was developed, in which the N−X bonds generated in situ were used as difunctionalized reagents. The distinctive features of this multicomponent reaction include a simple green catalytic system, a spectral substrate range, and the late-stage modification of drug molecules. Most importantly, this umpolung radical cascade strategy exploits the in situ formation of Niodoamines that enable efficient alkene aminoiodination.

Rhodium‐Catalyzed C8‐Alkenylation of Isoquinolones with Maleimides

“…Maleimides are a core feature in numerous bioactive molecules and can act as an electrophile in Michael addition and electrocyclic reactions [7c,i] . Several reports on transition metal‐catalyzed alkenylation with maleimides have been established till date however, selectivity always remains a challenge [7a,b,d–h,k] . Due to the absence of syn ‐coplanar hydrogen, β ‐hydride elimination cannot take place, therefore, hydroarylation occurs preferentially [8a–c] .…”

Michael Addition and Oxidative Cross‐Coupling Reaction of α‐Oxo Ketene Dithioacetals and Maleimides: Switchable Synthesis of 3‐Alkenyl Succinimides and Maleimides

“…[5,6] Among them, the direct functionalization of maleimides is an important method for the synthesis of 3substituted succinimides [7] and maleimides. [8] To date, the alkylation and arylation of maleimides to prepare 3-alkyl or aryl succinimides and maleimides have been well-documented, but there are only a few reports on their alkenylation probably due to the low reactivity of an alkenyl CÀ H bond. [9,10] In fact, compared with alkyl and aryl group, alkenyl moiety is among the most synthetically useful motif in organic synthesis because it is easily functionalized by numerous methods.…”

Recent advances in transition-metal-catalyzed directed C–H alkenylation with maleimides

“…Besides, maleimide is also an essential heterocyclic structural unit widely applied in organic synthesis. 2 As internal electron-deficient alkenes, maleimides have been extensively used as electrophiles for Michael additions and electrocyclic reactions. 3 In recent years, maleimides have been deeply investigated to access various compounds by means of transition-metal-catalyzed C–H bond activation, 4 which avoids the multistep sequences and cumbersome synthesis of maleimide/succinimide containing compounds.…”