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Solution-phase synthesis of a diverse isocoumarin library.

ABSTRACT: The solution-phase synthesis of a 167-member library of isocoumarins is described. The key intermediates for library generation, 4-iodoisocoumarins, are easily prepared by iodocyclization of the corresponding 2-(1-alkynyl)arenecarboxylate esters. The 4-iodoisocoumarins undergo palladium-catalyzed Sonogashira, Suzuki-Miyura, and Heck reactions to yield a diverse set of isocoumarins. Alternatively, isocoumarins, bearing hydroxyl or bromine functionalities, have been prepared by ZnCl(2)- and Pd(PPh(3))(4)-mediated cyclization of the corresponding o-iodobenzoic acid and appropriate terminal alkynes. The resulting isocoumarins were further diversified by derivatization of the hydroxyl or bromine groups. A small set of isoquinolinones were also prepared from the corresponding isocoumarins.

SUBMITTER: Roy S

PROVIDER: S-EPMC2785110 | biostudies-literature | 2009 Nov-Dec

REPOSITORIES: biostudies-literature

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Solution-phase synthesis of a diverse isocoumarin library.

Roy Sujata S Roy Sudipta S Neuenswander Benjamin B Hill David D Larock Richard C RC

Journal of combinatorial chemistry 20091101 6

The solution-phase synthesis of a 167-member library of isocoumarins is described. The key intermediates for library generation, 4-iodoisocoumarins, are easily prepared by iodocyclization of the corresponding 2-(1-alkynyl)arenecarboxylate esters. The 4-iodoisocoumarins undergo palladium-catalyzed Sonogashira, Suzuki-Miyura, and Heck reactions to yield a diverse set of isocoumarins. Alternatively, isocoumarins, bearing hydroxyl or bromine functionalities, have been prepared by ZnCl(2)- and Pd(PPh ...[more]

PMID: 19817453

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