These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
Zhu-ChemRxiv.pdf (485.72 kB)
Rh(III)-Catalyzed Coupling of N-Chloroimines with α-Diazo-α-Phosphonoacetates for Skeleton-Oriented Synthesis of 2H-Isoindoles
Preprints are manuscripts made publicly available before they have been submitted for formal peer review and publication. They might contain new research findings or data. Preprints can be a draft or final version of an author's research but must not have been accepted for publication at the time of submission.
revised on 18.07.2019 and posted on 18.07.2019by Bing Qi, Lei Li, Qi Wang, Wenjing Zhang, Lili Fang, Jin Zhu
A major hurdle for realizing the full potential of transition metalcatalyzed, directed C-H functionalization synthesis of heterocycles is the blockingof ability for designated structural elaboration by the reactivity-assisting groupderived, unintended appendages. We communicate herein Rh(III)-catalyzed coupling of N-chloroimines with α-diazo-α-phosphonoacetates for skeletonoriented synthesis (SOS) of 2H-Isoindoles. Comprehensive mechanistic studies with rhodacycle intermediates support an associative covalent relay mechanism for this first reported N-chloroimine-directed C-H functionalization reaction. Theinitial dechlorination/dephosphonation under Rh(III) catalysis and subsequent deesterification under Ni(II) catalysis allow the complete elimination of unintended appendages and full exposure of reactivity for C3 and N2 ring atoms. The proofof - concept utility has been demonstrated with electrophilic substitution at the C3 site (formylation, azo derivatization) and nucleophilic reaction (methylation) at the N2 site, showcasing the enormous synthetic potential of SOS for attaching structurally unrelated appendages and enabling entry to distinct chemical space.