Heterocyclic cores such as indole, benzofuran and benzothiophene are found in a large number of pharmaceuticals and polycyclic natural products.1 The [2+2] cycloaddition reaction is a versatile strategy for constructing architecturally interesting, sp3 rich cyclobutane-fused scaffolds for use in drug discovery programs.2,3 This presentation summarizes our on-going work on developing general visible-light photocatalytic platforms for non-dearomative and dearomative intra- and inter-molecular [2+2] cycloaddition reactions to construct novel three-dimensional molecular scaffolds.2-4 DFT calculations were used to compute the T1−S0 free energy gap of substrates and also to predict their reactivities based on triplet state energy transfer and transition state energy feasibility. The discovery of these photocatalytic transformations provides straightforward access to a broad array of stereodefined, drug-like complex molecular scaffolds from readily available starting materials and offers new opportunities for the derivatization of heterocycles and the exploration of new chemical space.

Photocatalytic [2+2] cycloaddition for building cyclobutane-fused three-dimensional molecular complexity

ACS Spring Meeting 2021

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