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Evaluating the Viability of Successive Ring‐Expansions Based on Amino Acid and Hydroxyacid Side‐Chain Insertion
Author(s) -
Lawer Aggie,
Epton Ryan G.,
Stephens Thomas C.,
Palate Kleopas Y.,
Lodi Mahendar,
Marotte Emilie,
Lamb Katie J.,
Sangha Jade K.,
Lynam Jason M.,
Unsworth William P.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202002164
Subject(s) - ring (chemistry) , side chain , scope (computer science) , chemistry , substrate (aquarium) , combinatorial chemistry , computational chemistry , computer science , organic chemistry , programming language , oceanography , geology , polymer
Abstract The outcome of ring‐expansion reactions based on amino/hydroxyacid side‐chain insertion is strongly dependent on ring size. This manuscript, which builds upon our previous work on Successive Ring Expansion (SuRE) methods, details efforts to better define the scope and limitations of these reactions on lactam and β‐ketoester ring systems with respect to ring size and additional functionality. The synthetic results provide clear guidelines as to which substrate classes are more likely to be successful and are supported by computational results, using a density functional theory (DFT) approach. Calculating the relative Gibbs free energies of the three isomeric species that are formed reversibly during ring expansion enables the viability of new synthetic reactions to be correctly predicted in most cases. The new synthetic and computational results are expected to support the design of new lactam‐ and β‐ketoester‐based ring‐expansion reactions.