Accessing pyrroles by the O-to-C skeletal edit of isoxazoles

Accessing pyrroles by the O-to-C skeletal edit of isoxazoles

Despite their ostensible similarity as five-membered heterocycles, isoxazoles and pyrroles differ vastly in their synthetic approaches. Because of their electronically dissonant backbone, pyrrole syntheses often require challenging starting materials or umpolung reactivity. Isoxazoles, on the other hand, have an electronically consonant backbone, enabling a much wider range of available syntheses using simple starting materials. This work bridges synthetically accessible isoxazoles with their less accessible pyrrole counterparts in an O-to-C skeletal edit. Our investigations of this reaction led to the revision of a previously established mechanism for pyrrole formation, supported by experimental and computational results. Further studies revealed an interesting side reaction, and from this a predictive model for reaction outcome was developed, deepening our understanding of both reactions. Overall, this transformation maps the readily accessible substitution pattern of isoxazoles onto more traditionally challenging pyrroles using skeletal editing.

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