Electronic tuning of site-selectivity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-11-11

AUTHORS

Brandon C. Wilcock, Brice E. Uno, Gretchen L. Bromann, Matthew J. Clark, Thomas M. Anderson, Martin D. Burke

ABSTRACT

Site-selective functionalizations of complex small molecules can generate targeted derivatives with exceptional step efficiency, but general strategies for maximizing selectivity in this context are rare. Here, we report that site-selectivity can be tuned by simply modifying the electronic nature of the reagents. A Hammett analysis is consistent with linking this phenomenon to the Hammond postulate: electronic tuning to a more product-like transition state amplifies site-discriminating interactions between a reagent and its substrate. This strategy transformed a minimally site-selective acylation reaction into a highly selective and thus preparatively useful one. Electronic tuning of both an acylpyridinium donor and its carboxylate counterion further promoted site-divergent functionalizations. With these advances, we achieve a range of modifications to just one of the many hydroxyl groups appended to the ion channel-forming natural product amphotericin B. Thus, electronic tuning of reagents represents an effective strategy for discovering and optimizing site-selective functionalization reactions. More... »

PAGES

996-1003

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nchem.1495

DOI

http://dx.doi.org/10.1038/nchem.1495

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1001259256

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23174979


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