Preparation of meta-cyclophanes via stereospecific ring-expansion rearrangement

meta-Cyclophanes represent a ubiquitous and versatile structural motif in macrocycles. While conventional synthetic strategies predominantly rely on end-to-end cyclization, these methods are often hampered by unfavourable enthalpic and entropic constraints, and are limited to unstrained meta-cyclophanes. Here we present an aryne-mediated ring-expansion strategy based on sequential aryne insertion into the S=O bond of cyclic sulfoxides followed by an anionic [4,5]-sigmatropic rearrangement. A pivotal aspect of this strategy is the ability of the generated phenolate oxygen to redirect the rearrangement pathway from a [5,5]- to an anionic [4,5]-sigmatropic rearrangement. This methodology enables efficient access to strained meta-cyclophanes with diverse substitution patterns. Moreover, it not only supports the use of meta-cyclophane-based aryne precursors but also enables the orthogonal assembly of a secondary cyclophane ring on the antipodal face of the central benzene scaffold. Furthermore, a chirality transfer process is observed, underscoring the stereospecific nature of both the S=O bond insertion and the [4,5]-sigmatropic rearrangement steps. meta-Cyclophane synthesis is often restricted to unstrained systems owing to unfavourable energetic constraints. Now the preparation of strained analogues is shown via sequential aryne insertion into cyclic sulfoxides and an anionic [4,5]-sigmatropic rearrangement. This strategy enables the use of meta-cyclophane-based aryne precursors and the orthogonal assembly of double cyclophanes.