Four-membered nitrogen heterocycles such as azetidines possess unique properties that make them desirable for drug discovery and synthesis applications. However, synthesis of these compounds is challenging, limiting their applicability. While oxetanes and cyclobutanes are commonly synthesized by highly atom-economical light-mediated [2+2] reactions, this powerful methodology remains limited for the synthesis of azetidines via the aza Paternò-Büchi reaction. Herein we report the development of a visible-light mediated intermolecular aza Paternò-Buchi reaction, harnessing the triplet state of unique cyclic oximes, specifically 2-isoxazoline-3-carboxylates, as imine equivalents for the synthesis of unique azetidine products. Following energy transfer from an iridium photocatalyst, these cyclic oximes initiate [2+2] reactions with unactivated alkenes, allowing access to a broad range of azetidines with excellent yield. This method is mild, operationally simple, and broadly applicable. Importantly, these products can be easily converted to free monocyclic azetidines, offering a new approach to these desirable targets.

New developments in (aza) Paternò-Büchi reactions

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