In this section
@article{Sahay:2025:10.1039/d5qo00804b,
author = {Sahay, AK and Begg, CS and Zhang, X and Bull, JA and Spivey, AC},
doi = {10.1039/d5qo00804b},
journal = {Organic Chemistry Frontiers},
title = {Structurally divergent reactivity of 2,2-disubstituted azetidines – mechanistic insights and stereochemical implications of amide coupling and ring expansion to 5,6-dihydro-4H-1,3-oxazines},
url = {http://dx.doi.org/10.1039/d5qo00804b},
year = {2025}
}
TY - JOUR
AB - Azetidines have gained traction in drug discovery for their ability to introduce conformational constraint and modulate physiochemical properties. Strategies that enable their selective functionalization or controlled expansion into more complex scaffolds provide opportunities for molecular diversification to rapidly access new chemical space. Subjecting 2,2-disubstituted azetidines to amide coupling with carboxylic acids is found to effect either N-acylation or ring expansion to spiro and 6,6-disubstituted 5,6-dihydro-4H-1,3-oxazine, dependent on reaction conditions. A diverse range of topologically interesting heterocycles, which hold significant potential for pharmaceutical screening, have been prepared using this divergent reaction manifold. A mechanistic framework, supported by additive screening and trapping experiments, is presented to account for the ring expansion and racemization that accompanies these transformations when the substrate allows formation of a ring-opened azafulvenium intermediate.
AU - Sahay,AK
AU - Begg,CS
AU - Zhang,X
AU - Bull,JA
AU - Spivey,AC
DO - 10.1039/d5qo00804b
PY - 2025///
SN - 2052-4129
TI - Structurally divergent reactivity of 2,2-disubstituted azetidines – mechanistic insights and stereochemical implications of amide coupling and ring expansion to 5,6-dihydro-4H-1,3-oxazines
T2 - Organic Chemistry Frontiers
UR - http://dx.doi.org/10.1039/d5qo00804b
UR - https://doi.org/10.1039/d5qo00804b
ER -
Email: a.c.spivey@imperial.ac.uk
Tel & Fax: +44 (0)20 75945841
Further links: