Asymmetric Organocatalytic Tandem Reaction to Chiral Pyrimidinone Derivatives using Urea as Dinitrogen Source

Abstract

A facile method for the asymmetric synthesis of pyrimidinone derivatives was developed via an organocatalytic tandem aza-Michael addition-hemiaminal formation-dehydroxylation reaction, using N,N'-dialkyloxyurea as dinitrogen source (up to 97% ee). The transformations of hemiaminal intermediates to pyrimidinones with more complex structures have been also investigated.

Recent Developments in Asymmetric Organocatalytic Domino Reactions

“…[68] The domino reaction, catalyzed by amine (S)-3 in the presence of acetic acid, afforded the corresponding hemiaminals 121a-d, which were subsequently submitted to dehydroxylation by treatment with Et 3 SiH/BF 3 which was directly added to the reaction, thus providing the corresponding pyrimidinones 122a-d in both excellent yields and enantioselectivities of up to 97% ee, as shown in Scheme 33.…”

Acyclic and Cyclic Ureas (Update 2013)

“…[190] This reaction is mediated by a chiral pyrrolidine derivative. It is quite tolerant with respect to the nature of the a,b-unsaturated aldehyde and usually affords the product under mild conditions in excellent yield (82-95%) and enantioselectivity (83-97%).…”

“…Dialkoxyurea and a,b-Unsaturated Aldehydes [190] Isocyanates react with 5-azanorbornenes in benzene at reflux to afford annulated pyrimidin-2-ones via a 1,3-diaza-Claisen rearrangement. At higher temperatures, a triazinone is observed as a byproduct.…”

Facile Synthesis of Chiral Cyclic Ureas through Hydrogenation of 2‐Hydroxypyrimidine/Pyrimidin‐2(1H)‐one Tautomers

“…[5] Notably,in2010, amethod for the asymmetric synthesis of chiral cyclic urea derivatives via an organocatalytic tandem aza-Michael additionhemiaminal formation and dehydroxylation cascade was successfully developed by Chen and co-workers. [6] Very recently,R ovis group developed an elegant rhodiumcatalyzed [4+ +2] cycloaddition between a,b-unsaturated imines and isocyanates to generate the chiral DHPMs in good yields and high enantioselectivities. [7] Despite these successful examples,g iven the great importance of chiral cyclic ureas,i tr emains indispensable to find new effective approaches to prepare structurally diverse chiral cyclic ureas derivatives with excellent enantioselectivity.…”