Synthesis of a NewN‐Diaminophosphoryl‐N′‐[(2S)‐2‐pyrrolidinylmethyl]thiourea as a Chiral Organocatalyst for the Stereoselective Michael Addition of Cyclohexanone to Nitrostyrenes and Chalcones – Application in Cascade Processes for the Synthesis of Polycyclic Systems

Abstract

A highly diastereoselective and enantioselective Michael addition of enolizable ketones such as cyclohexanone and acetophenone to a variety of substituted trans‐β‐nitrostyrenes and chalcones was catalyzed by a novel chiral and unsymmetrical thiourea as organocatalyst in the presence of water or under neat reaction conditions. The anticipated Michael adducts, γ‐nitrocarbonyl adducts and 1,5‐dicarbonyl derivatives, were obtained in up to 98:2 diastereomeric ratio and up to 96 % enantiomeric excess. The application of this new chiral organocatalyst was extended to an asymmetric Michael addition‐proton transfer‐aldol reaction cascade process, a formal [3+3] cyclization reaction of cyclohexanone with arylidenepyruvates, with high stereoselectivity. The organocatalyst reported here is one of the very few able to promote the above cascade process, providing the important bicyclic framework that is found in many natural products.

Recent Advances in Organocatalytic Asymmetric Michael Addition Reactions to α, β‐Unsaturated Nitroolefins

“…The intermediate A of the reaction is described in scheme 15 to obtain the final products (Scheme 15). [62] Ramapanicker et al in 2019 prepared a more effective trifluoromethanesulfonamide (À NHTf) based peptide catalyst 65 for the asymmetric Michael addition reaction of aldehydes 62 to nitroalkenes 63. This transformation has produced a series of chiral nitro aldehydes 64 in excellent yield with high selectivity.…”

Further developments of β,γ-unsaturated α-ketoesters as versatile synthons in asymmetric catalysis

“…Interestingly, a weak base as an additive was necessary to enhance the yields. Later, the asymmetric [3 + 3] annulation reactions of β,γ -unsaturated α -ketoesters and cyclohexanones for the synthesis of bridged compounds were reported by the Juaristi group ( Cruz-Hernández et al., 2018 ; Obregón-Zúñiga et al., 2017 ). Because pyrazolones were frequently found as an important structural unit in a variety of valuable nitrogen heterocycles, α , β -unsaturated pyrazolones possessing a γ-hydrogen have been employed as nucleophiles in organic synthesis.…”

Chiral Thioureas—Preparation and Significance in Asymmetric Synthesis and Medicinal Chemistry

“…Other chiral phosphorus derivatives of thioureas are also worth mentioning. Two phosphorylamide derivatives were prepared by Juaristi and co-workers and utilized in stereoselective Michael addition of cyclohexanone to nitrostyrenes and chalcones [42]. Chiral thioureas containing an aminophosphonate moiety were investigated in context of their antiviral activity as well [320].…”