title: Efficient Construction of Azaspiro[4.5]trienone Libraries via Tandem Ugi 4CC/Electrophilic ipso-Iodocyclization in One-Pot.
abstract: A solution-phase parallel synthesis of pharmaceutically important azaspiro[4.5]trienones has been developed by performing tandem Ugi four-component condensation (U4CC), involving substituted p-anisidines, aldehydes, 3-alkyl/aryl-propiolic acids, and isocyanides, and iodine-mediated ipso-iodocyclization in one-pot. This highly atom economical process produced functionalized azaspiro[4.5]trienones in good to excellent overall yields and products were easily isolated by precipitation followed by crystallization. These vinyl-iodide bearing azaspiro[4.5]trienones were utilized for further modifications through Suzuki coupling and deiodination reaction to demonstrate the suitability of these products for various palladium catalyzed modifications. The present method provides an easy access to highly functionalized azaspiro[4.5]trienones that can be useful in drug discovery research.
authors.affiliation: †Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India.|‡Academy of Scientific and Innovative Research, New Delhi-110025, India.
authors.forename: D
authors.initials: D
authors.lastname: Yugandhar
authors.affiliation: †Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India.|‡Academy of Scientific and Innovative Research, New Delhi-110025, India.
authors.forename: Ajay Kumar
authors.initials: AK
authors.lastname: Srivastava
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D000480:Alkynes / Q000737:chemistry*; D000814:Aniline Compounds / Q000737:chemistry*; D003486:Cyanides / Q000737:chemistry*; D003500:Cyclization; D015394:Molecular Structure; D011422:Propionates / Q000737:chemistry*; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000447:Aldehydes; D000480:Alkynes; D000814:Aniline Compounds; D003486:Cyanides; D011422:Propionates; D011760:Pyrrolidinones; D054852:Small Molecule Libraries; D013141:Spiro Compounds; C013813:4-anisidine; C011537:propiolic acid
keywords: Spiro compounds; Suzuki coupling; U4CC; Ugi reaction; ipso-iodocyclization; multicomponent reaction (MCR)