An Enantioselective Synthesis of 2-Imidazolidinones through Bifunctional Thiourea-Catalyzed Tandem Mannich/Cyclization of Isocyanatomalonate Diester

Abstract

A chiral bifunctional thiourea-catalyzed Mannich reaction of diethyl 2-isocyanatomalonate with N-sulfonylimines was described. The tandem cyclization proceeded smoothly after Mannch reaction, directly furnishing chiral 2-imidazolidinones in 72-99% yields with 83-98% ees. Sterically demanding sulfonyl group was crucial for aliphatic imines to afford the corresponding product in high enantioselectivity.

Asymmetric Synthesis of Spirooxazolidinone Oxindoles by the Thiourea‐Catalyzed Aldol Reaction of 2‐Isocyanatomalonate Diesters

“…In 2014, Takemoto's group reported the asymmetric aldol reaction of 2‐isocyanatomalonate esters with aldehydes in the presence of a thiourea catalyst, [10] and then our group has used this strategy to the asymmetric synthesis of amphenicol antibiotics [11] . Subsequently, the [3+2] cyclization reaction of 2‐isocyanatomalonate esters with aldimines via the cinchona alkaloid‐derived catalyst was developed by Takemoto's group [12] . Later on, Pedro's group found that the reaction of 2‐isocyanatomalonate esters with unsaturated alkenes could give substituted chiral γ‐lactams using the Mg(OTf) 2 −BOX complex [13] .…”

“…[11] Subsequently, the [3 + 2] cyclization reaction of 2isocyanatomalonate esters with aldimines via the cinchona alkaloid-derived catalyst was developed by Takemoto's group. [12] Later on, Pedro's group found that the reaction of 2-isocyanatomalonate esters with unsaturated alkenes could give substituted chiral γlactams using the Mg(OTf) 2 À BOX complex. [13] However, the types of electrophiles used in these reactions have remained largely unexplored.…”

Organocatalytic formal [4 + 2] cycloaddition of o-quinone-methyl derivatives and 2-isocyanatomalonate diesters for the construction of chroman derivatives with adjacent quaternary chiral centers

“…It has been reported to react with several electrophiles via asymmetric cycloaddition reactions to construct five-membered nitrogen-containing heterocycles (Scheme 2b). 11–13 In 2014, Takemoto's group disclosed the thiourea-catalyzed asymmetric formal [3 + 2] cycloadddition reaction of 2-isocyanatomalonate diester with various aldehyde compounds for the first total synthesis of mycestericin C, 11 a , b and then our group successfully applied this strategy for the asymmetric synthesis of amphenicol antibiotics and chiral spirooxazolidinone oxindole. 12 Subsequently, a chiral bifunctional thiourea-catalyzed Mannich/cyclization cascade reaction of 2-isocyanatomalonate diester with imine compounds was reported by Takemoto's group.…”