1208336-80-4Relevant academic research and scientific papers
Scope and limitations of an efficient four-component reaction for dihydropyridin-2-ones
Scheffelaar, Rachel,Parayidino, Monica,Znabet, Anass,Schmitz, Rob F.,De Kanter, Frans J. J.,Lutz, Martin,Spek, Anthony L.,Guerra, Celia Fonseca,Bickelhaupt, F. Matthias,Groen, Marinus B.,Ruijter, Eelco,Orru, Romano V. A.
, p. 1723 - 1732 (2010)
(Chemical Equation Presentation) A broad range of isonitrile-functionalized 3,4-dihydropyridin-2-ones could be prepared using a fourcomponent reaction between phosphonates, nitriles, aldehydes, and isocyanoacetates. The reaction involves initial formation of a 1-azadiene intermediate which is trapped in situ by an isocyanoacetate to give the desired heterocyclic scaffold through cyclocondensation. The full scope and limitations of this four-component reaction are described. Variation of the nitrile and aldehyde inputs proved to be extensively possible, but variation of the phosphonate input remains limited. Regarding the isocyanoacetate, a-aryl isocyanoacetates give moderate to high yields and result in a complete diastereoselectivity for the 3,4-cis isomer. α-Alkyl isocyanoacetates gave the corresponding dihydropyridin-2-ones in moderate yields, most of them as mixtures of diastereomers. Elevated temperatures during cyclocondensation generally increased the yield and resulted in a change of the diastereomeric ratio in favor of the cis-diastereomer. In addition to isocyanoacetates, a limited number of other α-acidic esters resulted in the formation of dihydropyridin-2-ones, albeit in much lower yield. Computational studies show that the observed difference in yield cannot be simply correlated to specific physical properties (including acidity) of the different α-acidic esters.
