Asymmetric Synthesis of 4,4-Disubstituted-2-Imidazoli-dinones:  Potent NK₁ Antagonists

Abstract

[structure: see text] A highly efficient and practical synthesis of 4,4-Disubstituted-2-Imidazolidinones utilizing a "self-reproduction of the center of chirality" strategy is described.

From new simple aliphatic to aromatic heterocycles built from 2-chloroethylisocyanate

“…That is the key intermediate 11 or II. Surface reactor drives the reaction to the obtainment of aliphatic imidazolidin-2-ones, present in many biologically active compounds [20][21][22][23] or pyrazines, part of many polycyclic compounds with biological or industrial significance [24]. Moreover, temperature tuning allows the modification of the selective yield of 2-methylpyrazine 18, which is the starting point to the formation of tubercular drugs [25], whose formation is maximized at low temperatures.…”

“…Once intermediate XIII is formed (path B), it releases HCl to give XIV and CO leading to the very reactive intermediates XV, from where the pyrazine heterocycle can be formed through XVI-XVIII. Desorption of this structure explains the formation of the radical hydro-1,4-pyrazine (30) which, for instance, could recombine with radical 23 allowing the formation of the other pyrazines (19)(20)(21)(22) after the loss of chlorine and hydrogen abstraction (Scheme 4).…”

Aliphatic aldehydes in the synthesis of carbo- and heterocycles. Part I. Synthesis of three-, four-, and five-membered rings

“…A convenient synthetic route to partly or completely hydrogenated imidazoles 100 is based on the reaction of aldehydes with 1,2-dicarbonyl compounds and their derivatives 101 and amines 102, as well as with 1,2-diamines (ortho-diamines) or related structures [90] [91][92][93][94][95][96][97][98][99][100][101][102][103][104], which were synthesized under mild conditions using novel reagents and catalysts [105][106][107][108][109][110][111][112][113] and under microwave irradiation [114][115][116][117] which ensured higher yields. Vicinal amino groups may be protected via facile conversion into the corresponding aminal and then deprotected by hydrolysis [118,119].…”

Gold(I)‐Catalyzed Intramolecular Hydroamination of N‐Allylic N′‐Arylureas to form Imidazolidin‐2‐ones

“…Substituted imidazolidin-2-ones are components of a number of biologically active compounds [1] including NK 1 and Muscarinic M3 antagonists, [2,3] HIV protease and human enterovirus 71 inhibitors, [4,5] and antiparasitic [6] and immunosuppressive agents. [7] Furthermore, chiral, non-racemic imidazolidin-2-ones have been employed as chiral auxiliaries [8,9] and as scaffolds for bis(phosphine) ligands [10,11] for use in enantioselective synthesis.…”