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Rethinking Hydrolytic Imidazoline Ring Expansion: A Common Approach to the Preparation of Medium-Sized Rings via Side-Chain Insertion into [1.4]Oxa- and [1.4]Thiazepinone Scaffolds

By Elena Reutskaya (6111311), Angelina Osipyan (5666825), Alexander Sapegin (4449556), Alexander S. Novikov (1616380) and Mikhail Krasavin (820851)


The previously reported ring-expansion strategy involving hydrolytically prone imidazoline rings was thought to include the formation of a hydrated imidazoline intermediate. In this work, we accessed the latter via the addition of a 2-aminoethyl side chain onto a lactam moiety. This led to an efficient three-atom ring expansion of diarene-fused [1.4]­oxazepines and [1.4]­thiazepines and led us to propose to term this common approach the hydrated imidazoline ring expansion (HIRE) reaction. The strategy was extended to the insertion of longer (containing up to five atoms) side chains, and thus, larger (11- to 12-membered) diarene-fused rings were obtained via the homo-HIRE and homo<sup>2</sup>-HIRE reactions, respectively. This underscores the utility of the HIRE reaction for the preparation of medium-sized rings, an important class of chemical tools for interrogation of various biological targets

Topics: Biophysics, Biochemistry, Genetics, Pharmacology, Biotechnology, Evolutionary Biology, Sociology, Plant Biology, Chemical Sciences not elsewhere classified, HIRE reactions, imidazoline ring expansion, diarene-fused rings, homo 2, HIRE reaction, Side-Chain Insertion, Medium-Sized Rings, Rethinking Hydrolytic Imidazoline Ring Expansion, side chains, 2- aminoethyl side chain, lactam moiety, three-atom ring expansion, chemical tools, Common Approach, imidazoline rings, ring-expansion strategy, 12- membered
Year: 2018
DOI identifier: 10.1021/acs.joc.8b02805.s007
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Provided by: FigShare
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