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 (11to 12-membered) diarene-fused rings were obtained via the homo-HIRE and homo 2 -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.

A four‐step approach to the “hydrated imidazoline ring expansion” (HIRE) is presented. In most cases, the ring expansion was the sole process. However, for the first time, an alternative course of the hydrated imidazoline evolution was discovered which gave N‐aminoethyl derivatives. These can, in principle, be converted into the target HIRE products under sufficiently forcing conditions. The approach offers improved flexibility with respect to the peripheral substituents and is also applicable to the synthesis of eleven‐membered lactams. We observed that the latter can exist in two stable isomeric forms due to lactam–amide bond isomerization. The latter finding further demonstrates the value of medium‐sized rings as multiple‐conformer probes for biological target interrogation.

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Both carbon and nitrogen centers in the coordinated isocyano group are capable of acting as a π-hole donor toward lone pairs.

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