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Carbon Atom Insertion into Pyrroles and Indoles Promoted by Chlorodiazirines
[Image: see text] Herein, we report a reaction that selectively generates 3-arylpyridine and quinoline motifs by inserting aryl carbynyl cation equivalents into pyrrole and indole cores, respectively. By employing α-chlorodiazirines as thermal precursors to the corresponding chlorocarbenes, the trad...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343525/ https://www.ncbi.nlm.nih.gov/pubmed/34286965 http://dx.doi.org/10.1021/jacs.1c06287 |
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author | Dherange, Balu D. Kelly, Patrick Q. Liles, Jordan P. Sigman, Matthew S. Levin, Mark D. |
author_facet | Dherange, Balu D. Kelly, Patrick Q. Liles, Jordan P. Sigman, Matthew S. Levin, Mark D. |
author_sort | Dherange, Balu D. |
collection | PubMed |
description | [Image: see text] Herein, we report a reaction that selectively generates 3-arylpyridine and quinoline motifs by inserting aryl carbynyl cation equivalents into pyrrole and indole cores, respectively. By employing α-chlorodiazirines as thermal precursors to the corresponding chlorocarbenes, the traditional haloform-based protocol central to the parent Ciamician-Dennstedt rearrangement can be modified to directly afford 3-(hetero)arylpyridines and quinolines. Chlorodiazirines are conveniently prepared in a single step by oxidation of commercially available amidinium salts. Selectivity as a function of pyrrole substitution pattern was examined, and a predictive model based on steric effects is put forward, with DFT calculations supporting a selectivity-determining cyclopropanation step. Computations surprisingly indicate that the stereochemistry of cyclopropanation is of little consequence to the subsequent electrocyclic ring opening that forges the pyridine core, due to a compensatory homoaromatic stabilization that counterbalances orbital-controlled torquoselectivity effects. The utility of this skeletal transform is further demonstrated through the preparation of quinolinophanes and the skeletal editing of pharmaceutically relevant pyrroles. |
format | Online Article Text |
id | pubmed-8343525 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-83435252021-08-09 Carbon Atom Insertion into Pyrroles and Indoles Promoted by Chlorodiazirines Dherange, Balu D. Kelly, Patrick Q. Liles, Jordan P. Sigman, Matthew S. Levin, Mark D. J Am Chem Soc [Image: see text] Herein, we report a reaction that selectively generates 3-arylpyridine and quinoline motifs by inserting aryl carbynyl cation equivalents into pyrrole and indole cores, respectively. By employing α-chlorodiazirines as thermal precursors to the corresponding chlorocarbenes, the traditional haloform-based protocol central to the parent Ciamician-Dennstedt rearrangement can be modified to directly afford 3-(hetero)arylpyridines and quinolines. Chlorodiazirines are conveniently prepared in a single step by oxidation of commercially available amidinium salts. Selectivity as a function of pyrrole substitution pattern was examined, and a predictive model based on steric effects is put forward, with DFT calculations supporting a selectivity-determining cyclopropanation step. Computations surprisingly indicate that the stereochemistry of cyclopropanation is of little consequence to the subsequent electrocyclic ring opening that forges the pyridine core, due to a compensatory homoaromatic stabilization that counterbalances orbital-controlled torquoselectivity effects. The utility of this skeletal transform is further demonstrated through the preparation of quinolinophanes and the skeletal editing of pharmaceutically relevant pyrroles. American Chemical Society 2021-07-21 2021-08-04 /pmc/articles/PMC8343525/ /pubmed/34286965 http://dx.doi.org/10.1021/jacs.1c06287 Text en © 2021 American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Dherange, Balu D. Kelly, Patrick Q. Liles, Jordan P. Sigman, Matthew S. Levin, Mark D. Carbon Atom Insertion into Pyrroles and Indoles Promoted by Chlorodiazirines |
title | Carbon
Atom Insertion into Pyrroles and Indoles Promoted
by Chlorodiazirines |
title_full | Carbon
Atom Insertion into Pyrroles and Indoles Promoted
by Chlorodiazirines |
title_fullStr | Carbon
Atom Insertion into Pyrroles and Indoles Promoted
by Chlorodiazirines |
title_full_unstemmed | Carbon
Atom Insertion into Pyrroles and Indoles Promoted
by Chlorodiazirines |
title_short | Carbon
Atom Insertion into Pyrroles and Indoles Promoted
by Chlorodiazirines |
title_sort | carbon
atom insertion into pyrroles and indoles promoted
by chlorodiazirines |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343525/ https://www.ncbi.nlm.nih.gov/pubmed/34286965 http://dx.doi.org/10.1021/jacs.1c06287 |
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