Fischer Indole Synthesis Inspired De Novo and Modular Assembly of Indolines
- 1Southern University of Science and Technology , , ,
- 2Henan Normal University , , , ,
Abstract
Herein, we report a modular and redox-neutral strategy for the de novo synthesis of structurally diverse indolines. While conventional approaches often rely on prefunctionalized arenes or require oxidative/reductive steps, our method enables direct annulation from ortho-unsubstituted anilines and vinyldiazos. The sequence comprises a rhodium-catalyzed α-selective N–H insertion of vinyldiazoacetates, followed by TFA-promoted aza-Claisen rearrangement and intramolecular aza-Michael addition. This one-pot sequential protocol exhibits broad substrate generality and has been extended to an asymmetric version and intramolecular variant, allowing the synthesis of challenging seven-membered ring-fused indolines. DFT studies support a concerted mechanism via a chairlike transition state. With its operational simplicity and structural versatility, this methodology provides an efficient route to access privileged indoline scaffolds for pharmaceutical and synthetic applications.
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BibTeX
@article{long2026fischer,
title = {{Fischer Indole Synthesis Inspired De Novo and Modular Assembly of Indolines}},
author = {Haifeng Long and Peng Zhang and Meiling Huang and Weici Xu and Ming-Hua Xu},
journal = {ACS Central Science},
year = {2026},
month = oct,
doi = {10.1021/acscentsci.6c00925},
url = {https://pubs.acs.org/acscii/article/doi/10.1021/acscentsci.6c00925/5446816/Fischer-Indole-Synthesis-Inspired-De-Novo-and},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Fischer Indole Synthesis Inspired De Novo and Modular Assembly of Indolines
AU - Haifeng Long
AU - Peng Zhang
AU - Meiling Huang
AU - Weici Xu
AU - Ming-Hua Xu
PY - 2026
DA - 2026/10/08
JO - ACS Central Science
DO - 10.1021/acscentsci.6c00925
UR - https://pubs.acs.org/acscii/article/doi/10.1021/acscentsci.6c00925/5446816/Fischer-Indole-Synthesis-Inspired-De-Novo-and
AB - Herein, we report a modular and redox-neutral strategy for the de novo synthesis of structurally diverse indolines. While conventional approaches often rely on prefunctionalized arenes or require oxidative/reductive steps, our method enables direct annulation from ortho-unsubstituted anilines and vinyldiazos. The sequence comprises a rhodium-catalyzed α-selective N–H insertion of vinyldiazoacetates, followed by TFA-promoted aza-Claisen rearrangement and intramolecular aza-Michael addition. This one-pot sequential protocol exhibits broad substrate generality and has been extended to an asymmetric version and intramolecular variant, allowing the synthesis of challenging seven-membered ring-fused indolines. DFT studies support a concerted mechanism via a chairlike transition state. With its operational simplicity and structural versatility, this methodology provides an efficient route to access privileged indoline scaffolds for pharmaceutical and synthetic applications.
SN - 2374-7943
SN - 2374-7951
ER -