Pd(II)-Catalyzed Csp<sup>2</sup>–H Carbonylative Amidation of Groebke–Blackburn–Bienaymé Reaction Products: Access to Imidazo[1,2-<i>a</i>]pyridine-Fused δ-Lactams

The Groebke-Blackburn-Bienaymé (GBB) reaction provides efficient access to imidazole-fused heterocycles, yet it is inevitably endowed with an isocyanide-derived secondary amino group in products. Herein, we report a Pd(II)-catalyzed sp<sup>2</sup> C-H carbonylative amidation strategy using Co<sub>2</sub>(CO)<sub>8</sub> as a safe CO surrogate. Leveraging the native aryl amino group as a directing motif, this protocol enables direct conversion of GBB adducts into pharmaceutically relevant imidazo[1,2-<i>a</i>]pyridine-fused δ-lactams with up to 86% yield. The method demonstrates exceptional functional group tolerance and eliminates prefunctionalization requirements, offering a streamlined approach to access complex nitrogen-rich architectures.

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Publication Details

Journal
The Journal of Organic Chemistry
Published
2025-09-13
DOI
https://doi.org/10.1021/acs.joc.5c01662
Primary Topic
Nanomaterials for catalytic reactions
Type
article
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article

Pd(II)-Catalyzed Csp2–H Carbonylative Amidation of Groebke–Blackburn–Bienaymé Reaction Products: Access to Imidazo[1,2-a]pyridine-Fused δ-Lactams

Xingang Xie, Wen Qin, Lingmeng Xie, Xing Huo et al.
The Journal of Organic Chemistry
Nanomaterials for catalytic reactions
article

Pd(II)-Catalyzed Csp2–H Carbonylative Amidation of Groebke–Blackburn–Bienaymé Reaction Products: Access to Imidazo[1,2-a]pyridine-Fused δ-Lactams

Xingang Xie, Wen Qin, Lingmeng Xie, Xing Huo, Jingru Zou
article en

Abstract

The Groebke-Blackburn-Bienaymé (GBB) reaction provides efficient access to imidazole-fused heterocycles, yet it is inevitably endowed with an isocyanide-derived secondary amino group in products. Herein, we report a Pd(II)-catalyzed sp<sup>2</sup> C-H carbonylative amidation strategy using Co<sub>2</sub>(CO)<sub>8</sub> as a safe CO surrogate. Leveraging the native aryl amino group as a directing motif, this protocol enables direct conversion of GBB adducts into pharmaceutically relevant imidazo[1,2-<i>a</i>]pyridine-fused δ-lactams with up to 86% yield. The method demonstrates exceptional functional group tolerance and eliminates prefunctionalization requirements, offering a streamlined approach to access complex nitrogen-rich architectures.

The Journal of Organic ChemistryVol. 90(38)
State Key Laboratory of Chemical Engineering (CN), Lanzhou University (CN)
Openalex Percentile: Top 82%
Nanomaterials for catalytic reactions
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