Diversity oriented synthesis of β-carbolinone and indolo-pyrazinone analogues based on an Ugi four component reaction and subsequent cyclisation of the resulting indole intermediate

• Published in: RSC advances 2016-01, Vol.6 (25), p.21165-21186
• Main Authors: Purohit, Pooja, Pandey, Anand Kumar, Kumar, Brijesh, Chauhan, Prem M. S
• Format: Article
• Language: English
• Subjects: Activation; Aromatic compounds; Derivatives; Dimethyl acetals; Heterocyclic compounds; Indoles; Synthesis; Synthesis (chemistry)
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/c5ra27090a

A one-pot domino multicomponent reaction for the rapid, integrated and versatile synthesis of highly functionalized β-carbolinones ( 9a-9ab ) and indolo-pyrazinones ( 10a-10ab ) has been established. The reaction involves an Ugi-four component reaction of indole 2-carboxylic acid ( 1 or 16a-c ), aryl or alkyl aldehyde ( 6a-p ), isocyanide ( 3a-e ), and aminoacetaldehyde dimethyl acetal ( 7 ) followed by in situ acid-mediated deprotection/activation/electrophilic cyclisation/and aromatisation. The products were obtained from Ugi adducts in good to excellent yield within short periods of 20-30 min at room temperature (35 °C). The potential of the methodology is proved by development of a diverse library of heterocyclic compounds with point and skeletal diversity. Moreover, the synthesis has also been accomplished using N -substituted derivatives of indole 2-carboxylic acid that delivers highly diverse N -substituted β-carbolinone ( 18a-l ) heterocycles of medicinal importance. One pot two step synthesis of β-carbolinone and indolo-pyrazinone analogues via acid mediated cyclisation of Ugi intermediate has been developed with a wide substrate scope.