Evaluating the Viability of Successive Ring-Expansions Based on Amino Acid and Hydroxyacid Side-Chain Insertion

TY - JOUR

T1 - Evaluating the Viability of Successive Ring-Expansions Based on Amino Acid and Hydroxyacid Side-Chain Insertion

AU - Lawer, Aggie

AU - Epton, Ryan G

AU - Stephens, Thomas C

AU - Palate, Kleopas Y

AU - Lodi, Mahendar

AU - Marotte, Emilie

AU - Lamb, Katie J

AU - Sangha, Jade K

AU - Lynam, Jason M

AU - Unsworth, William Paul

N1 - © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

PY - 2020/9/11

Y1 - 2020/9/11

N2 - 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.

AB - 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.

U2 - 10.1002/chem.202002164

DO - 10.1002/chem.202002164

M3 - Article

C2 - 32432817

SN - 0947-6539

SP - 1

EP - 11

JO - Chemistry : A European Journal

JF - Chemistry : A European Journal

ER -