Chiral Phosphoric Acid Catalyzed Asymmetric Desymmetrization of para-Quinamines with Isocyanates: Access to Functionalized Imidazolidin-2-one Derivatives

Abstract

The development of enantioselective desymmetrization of para-quinamines with isocyanates catalyzed by chiral phosphoric acid is reported. The strategy provides concise access to functionalized imidazolidin-2-one derivatives in high yields and enantioselectivities under mild reaction conditions. Remarkably, this reaction could be performed on a gram scale using 5 mol % catalyst loading and the chiral imidazolidin-2-one derivatives could be easily transformed into valuable scaffolds without disturbing the enantiopurity, demonstrating the synthetic utility of this protocol.

Asymmetric Organocatalyzed Intermolecular Functionalization of Cyclohexanone‐Derived Dienones

“…Para ‐quinamines have also been integrated in chiral phosphoric acid catalysis as shown by the report of Sun, Xu, Lai and co‐workers in 2021 (Scheme 7). [28] …”

“…Para-quinamines have also been integrated in chiral phosphoric acid catalysis as shown by the report of Sun, Xu, Lai and co-workers in 2021 (Scheme 7). [28] An enantioselective desymmetrization of para-quinamines 17 with isocyanates 18 was developed to produce functionalized imidazolidin-2-ones 19. After the optimization studies, good-to-excellent enantioselectivities were obtained with the chiral phosphoric acid catalyst cat-7 thanks to its large πsystem.…”

Synthesis of Functionalized Thiazolidin-2-imine and Oxazolidin-2-one Derivatives from p-Quinamines via [3 + 2] Annulation of Isothiocyanates and CO2

“…Isocyanates and isothiocyanates are versatile building blocks for the annulation reaction because of their unique ability to function as carbon electrophiles, and this chemistry has been extended to the use of isoselenocyanates and carbodiimides by Alper’s group . On the other hand, p -quinamines as a novel three-atom synthon for constructing nitrogen-containing heterocyclic ring systems have attracted considerable attention in the chemical community . In 2018, Huang’s group developed a DBU-catalyzed [3 + 2] annulation strategy between p -quinamines and isocyanates to construct a series of imidazolidine-2-one derivatives .…”

Synthesis of spirocyclic 1,2-diamines by dearomatising intramolecular diamination of phenols

“…While the intramolecular aza-Michael reaction of amides, carbamates and sulfonamides to cyclohexadienones has been widely exploited in biomimetic and other syntheses, 9,10 there is to our knowledge only one example of a urea acting as a nucleophile, and this involved sequential dearomatisation and urea formation/asymmetric cyclisation reactions. 11…”

“…While the intramolecular aza-Michael reaction of amides, carbamates and sulfonamides to cyclohexadienones has been widely exploited in biomimetic and other syntheses, 9,10 there is to our knowledge only one example of a urea acting as a nucleophile, and this involved sequential dearomatisation and urea formation/asymmetric cyclisation reactions. 11 The intended products contain substructures that are embedded in a number of biologically-relevant skeleta. Vicinal 1,2-diamines are common motifs in many drugs and functional molecules, 12 and the 1,2-diaminocyclohexane structure is found in small molecule bioactives such as the anti-coagulant edoxaban 13 and the CCR2 antagonist BMS-741672 14 (Fig.…”