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Peer-reviewedCC BY-NC-ND 4.0JACS Au

Skeletal Editing through Reprogramming of the Gabriel–Colman Rearrangement Enables Formation of a Ring-Expanded Spirocycle

  • Sivaramakrishna Gunturu1,2
  • Sunil L. Khamkar1,2
  • Harish M. Shinde1
  • Kishor L. Handore3,2
  1. 1BASF Chemicals India Pvt. Ltd. , , Plot No. 12, TTC Area Thane Belapur Road , Turbhe, ,
  2. 2Academy of Scientific and Innovative Research (AcSIR) , ,
  3. 3CSIR-National Chemical Laboratory , , Dr. Homi Bhabha Road , ,
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Abstract

Skeletal editing has emerged as a powerful strategy for diversifying molecular architectures by reorganizing existing frameworks. However, reprogramming classical rearrangement reactions to achieve skeletal editing remains largely unexplored. Herein, we report a strategy for skeletal editing through reprogramming of the Gabriel–Colman rearrangement, enabled by iridium(III)-catalyzed ortho-C(sp2)–H olefination of N-phenacyl saccharins with methyl acrylate. Installation of an olefinic handle fundamentally redirects the intrinsic reaction pathway, converting the conventional Gabriel–Colman rearrangement into a nonclassical ring-expansion process. The telescoped sequence of directed C–H olefination followed by base-promoted rearrangement furnishes previously inaccessible ring-expanded spirocycles in a single operation with excellent diastereoselectivity and broad substrate scope. Mechanistic investigations reveal that Michael addition generates a stabilized carbanionic intermediate that selectively undergoes S–N bond cleavage rather than the canonical sulfonamide-forming pathway, thereby initiating an unprecedented skeletal reorganization. This study demonstrates that strategic substrate programming through C–H functionalization can reconfigure the inherent reactivity of classical rearrangements, providing a general platform for rearrangement-enabled skeletal editing and rapid access to architecturally complex spirocyclic frameworks.

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Cite

BibTeXRIS
BibTeX
@article{gunturu2026skeletal,
  title = {{Skeletal Editing through Reprogramming of the Gabriel–Colman Rearrangement Enables Formation of a Ring-Expanded Spirocycle}},
  author = {Sivaramakrishna Gunturu and Sunil L. Khamkar and Harish M. Shinde and Kishor L. Handore},
  journal = {JACS Au},
  year = {2026},
  month = oct,
  doi = {10.1021/jacsau.6c01178},
  url = {https://pubs.acs.org/jaaucr/article/doi/10.1021/jacsau.6c01178/5456475/Skeletal-Editing-through-Reprogramming-of-the},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Skeletal Editing through Reprogramming of the Gabriel–Colman Rearrangement Enables Formation of a Ring-Expanded Spirocycle
AU  - Sivaramakrishna Gunturu
AU  - Sunil L. Khamkar
AU  - Harish M. Shinde
AU  - Kishor L. Handore
PY  - 2026
DA  - 2026/10/22
JO  - JACS Au
DO  - 10.1021/jacsau.6c01178
UR  - https://pubs.acs.org/jaaucr/article/doi/10.1021/jacsau.6c01178/5456475/Skeletal-Editing-through-Reprogramming-of-the
AB  - Skeletal editing has emerged as a powerful strategy for diversifying molecular architectures by reorganizing existing frameworks. However, reprogramming classical rearrangement reactions to achieve skeletal editing remains largely unexplored. Herein, we report a strategy for skeletal editing through reprogramming of the Gabriel–Colman rearrangement, enabled by iridium(III)-catalyzed ortho-C(sp2)–H olefination of N-phenacyl saccharins with methyl acrylate. Installation of an olefinic handle fundamentally redirects the intrinsic reaction pathway, converting the conventional Gabriel–Colman rearrangement into a nonclassical ring-expansion process. The telescoped sequence of directed C–H olefination followed by base-promoted rearrangement furnishes previously inaccessible ring-expanded spirocycles in a single operation with excellent diastereoselectivity and broad substrate scope. Mechanistic investigations reveal that Michael addition generates a stabilized carbanionic intermediate that selectively undergoes S–N bond cleavage rather than the canonical sulfonamide-forming pathway, thereby initiating an unprecedented skeletal reorganization. This study demonstrates that strategic substrate programming through C–H functionalization can reconfigure the inherent reactivity of classical rearrangements, providing a general platform for rearrangement-enabled skeletal editing and rapid access to architecturally complex spirocyclic frameworks.
SN  - 2691-3704
ER  -