A Cross-Metathesis/Aza-Michael Reaction Strategy for the Synthesis of Cyclic and Bicyclic Ureas

Abstract

The synthesis of cyclic and bicyclic ureas via a ruthenium-catalyzed cross-metathesis / aza-Michael reaction strategy between protected alkenyl ureas and Michael acceptors is described. The substrates for these reactions are generated in 1-3 steps from commercially available materials, and products are formed in moderate yield with up to >20:1 diastereoselectivity.

Copper(I)-Catalyzed Cross-Coupling of 1-Bromoalkynes with N-Heterocyclic Organozinc Reagents

“…Unlike previously reported methods, the Zn(II)-mediated metalloamination/cyclization cascade does not rely on transient intermediates that limit the following functionalization to only those electrophiles which react quickly and completely [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. The Zn(II) cascade generates a stable organozinc intermediate that can readily be transmetallated, resulting in the formation of a diverse repository of scaffolds.…”

“…We have previously reported one such method involving the use of Et2Zn in a mediated metalloamination/cyclization cascade with subsequent electrophilic fun ization (Scheme 1) [9][10][11]. Unlike previously reported methods, the Zn(II)-mediated metalloamination/ tion cascade does not rely on transient intermediates that limit the following func zation to only those electrophiles which react quickly and completely [12][13][14][15][16][17][18][19][20]. Th cascade generates a stable organozinc intermediate that can readily be transmet the formation of a diverse repository of scaffolds.…”

Recent Advances in the Catalytic Synthesis of Imidazolidin-2-ones and Benzimidazolidin-2-ones

“…This approach proceeds with the oxidation of the radical-centered carbon with the regeneration of the double bond after proton abstraction (Scheme 64). The aza-Michael strategy was also applied in the synthesis of enantioenriched β,γ-diamino acid derived imidazolidin-2-ones by Terada [178]. γ-Amino-α,β-unsaturated esters were caused to react with tosyl isocyanates in a formal [3 + 2] cycloaddition using 10% of DIPEA as the catalyst.…”

Transition Metal- and Base-Free Electrochemical aza-Michael Addition of Aromatic aza-Heterocycles or Ts-Protected Amines to α,β-Unsaturated Alkenes Mediated by NaI

“…Nitrogen-containing compounds are an important class of organic molecules and building blocks widely found in natural products, drug molecules, and functional materials. − Consequently, much effort has been devoted for their efficient syntheses, especially for the formation of diverse C–N bonds. − Among the methods developed, aza-Michael addition reactions prove to be one of the simplest and most effective approaches to the corresponding adducts, such as β-amino sulfone, β-amino nitrile, or β-amino carbonyl products, from readily available starting materials and with high atom- and step-economic character. − Since the poor nucleophilicity of aromatic aza-heteroarenes and aromatic amines, − the aza-Michael addition reactions are predominately limited to aliphatic amines. As a result, strong acidic or basic conditions, elevated reaction temperature or long reaction time are frequently utilized to promote the aza-Michael addition reactions of aromatic aza-heteroarenes and Ts-protected amines (Scheme , top). − These harsh conditions are not compatible to substrates containing acid- or base-sensitive functionalities.…”