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Tandem C(sp3)-H Arylation/Oxidation and Arylation/Allylic Substitution of Isoindolinones.

ABSTRACT: Isoindolinones comprise an important class of medicinally active compounds. Herein we report a straightforward functionalization of the isoindolinones with aryl bromides (22 examples) using a Pd(OAc)2/NIXANTPHOS-based catalyst system. Additionally 3-aryl 3-hydroxy isoindolinone derivatives, which exhibit anti-tumor activity, can be accessed via a tandem reaction. Thus, when the arylation product is exposed to air under basic conditions, in situ oxidation takes place to install the 3-hydroxyl group. Furthermore, a tandem arylation/allylic substitution reaction is advanced in which both the arylation and allylic substitution are catalyzed by the same palladium catalyst. Finally, a tandem arylation/alkylation procedure is presented. These tandem reactions enable the synthesis of a variety of structurally diverse isoindolinone derivatives from common starting materials.

SUBMITTER: Jimenez J

PROVIDER: S-EPMC5482541 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Tandem C(sp3)-H Arylation/Oxidation and Arylation/Allylic Substitution of Isoindolinones.

Jiménez Jacqueline J Kim Byeong-Seon BS Walsh Patrick J PJ

Advanced synthesis & catalysis 20160802 17

Isoindolinones comprise an important class of medicinally active compounds. Herein we report a straightforward functionalization of the isoindolinones with aryl bromides (22 examples) using a Pd(OAc)2/NIXANTPHOS-based catalyst system. Additionally 3-aryl 3-hydroxy isoindolinone derivatives, which exhibit anti-tumor activity, can be accessed via a tandem reaction. Thus, when the arylation product is exposed to air under basic conditions, in situ oxidation takes place to install the 3-h ...[more]

PMID: 28652858

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