A Three‐Component Reaction Based on a Remote‐Group‐Directed Dynamic Kinetic Aza‐Michael Addition: Stereoselective Synthesis of Imidazolidin‐4‐ones

Crystal structure, Hirshfeld surface analysis and PIXEL calculations of a 1:1 epimeric mixture of 3-[(4-nitrobenzylidene)amino]-2(R,S)-(4-nitrophenyl)-5(S)-(propan-2-yl)imidazolidin-4-one

“…Imidazolidin-4-ones have been widely studied (Blackmore & Thompson, 2011) due to their wide range of uses, for example, as chiral ligands in catalysis (Lin et al, 2013;Mondini et al, 2013;Seebach et al, 2008;Puglisi et al, 2013) and for their biological activities (Elrod & Worley, 1999;Gomes et al, 2004;Guerra et al, 2011;Barrow et al, 2007). As a consequence of their utility, there are a number of well-established synthetic routes, in particular those involving chiral synthesis (Blackmore & Thompson, 2011;Eyilcim et al, 2018;Li et al, 2004;Vale et al, 2008Vale et al, , 2009Catalano et al, 2011;Xu et al, 2010). As part of our studies on nitrogen-containing heterocyclic compounds, we report the crystal structure, Hirshfeld surface analysis and PIXEL calculations of a 1:1 epimeric mixture of 3-[(4-nitrobenzylidene)amino]-2(R,S)-(4-nitrophenyl)-5(S)-(propan-2-yl)imidazolidin-4-one, 1.…”

Asymmetric Domino Reactions Based on the Use of Chiral Substrates

“…135 Indeed, it is known that these products exhibit a range of biological activities and constitute key chiral building blocks for the total synthesis of medically important compounds. 136 The pyridyl moiety of the chiral auxiliary amino amide activated the Michael acceptor under acidic conditions, while acting as a remote directing group to position the enone and the secondary amine in a favourable orientation for the aza-Michael addition, as depicted in the occurrence of a dynamic kinetic pathway in which the reaction of the cis-intermediate was faster owing to reduced steric hindrance.…”

Preparation of Imidazolidin‐4‐ones and Their Evaluation as Hydrolytically Cleavable Precursors for the Slow Release of Bioactive Volatile Carbonyl Derivatives

“…A series of methods allowing the preparation of imidazolid- inones from amino acid amides with aldehydes or ketones have been described. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][30][31][32][33][34][35][36][37] According to the literature, imidazolidinones from aliphatic aldehydes or ketones were prepared in polar solvents such as dimethylformamide, [14] methanol, or ethanol [18][19][20][21][22] and, in particular, if the hydrochloride of the amino acid amide was used, they were prepared in the presence of a base (TEA or NaOH). [23][24][25][26] Pure products were obtained by acidic workup and column chromatography [14,[19][20][21]25,26] or by extraction and recrystallization.…”

“…[24] Alternatively, reactions were carried out in methanol or isopropanol by using zeolites, para-toluenesulfonic acid, acetic acid, or trifluoroacetic acid (TFA) as catalysts. [15][16][17] Imidazolidinones of sterically demanding pivalaldehyde were prepared under acidic conditions (in the presence of TFA) in dichloromethane or toluene [13,39] followed by basic workup and crystallization or chromatography to afford pure imidazolidinones in moderate to good yields. Other methods describe the reaction in benzene or toluene with the azeotropic removal of water, typically in the presence of an acidic catalyst.…”

“…Some single crystal structures of different imidazolidin-4-one derivatives have already been reported in the literature. [16][17][18][19]36] Compound (5S,6S,9R)-4a (200 mg, isolated from a pure chromatography fraction) was dissolved in a mixture of 0.5 mL of ethyl acetate and 2.5 mL of heptane and left to crystallize overnight. X-ray crystal structure analysis showed the presence of multiple twinned crystals, which were not suitable for single crystal X-ray diffraction.…”