Intermolecular Reductive Coupling of Ketones and Alkenes under Ferrioxalate Photocatalysis

Ketones and alkenes are among the most frequent functional groups found in natural products, feedstock, and bioactive compounds. Hence, the use of both functionalities as cross-coupling handles retains a marked synthetic potential for Csp³-Csp³ bond formation. However, the reaction between ketones and alkenes has traditionally relied on intramolecular systems or the use of activated coupling partners, while intermolecular reactions involving unbiased substrates have found limited success. Here we report a strategy for the direct coupling of unactivated ketones with unactivated alkenes enabled by ferrioxalate photocatalysis. This catalytic platform allows the inner-sphere reduction of ketones to access ketyl radicals that effectively react with alkenes despite the adverse polarity mismatch. This method gives access to a wide range of tertiary alcohols, which are generally assembled through Grignard reagent additions, using alkenes in place of organometallic nucleophiles, allowing this transformation to proceed with broad tolerance to diverse polar and protic functional groups. Overall, this reactivity blueprint constitutes a platform for the fast exploration of Csp³-rich chemical space, capitalizing on the diversity of readily available alkene and ketone building blocks. The utility of the method is demonstrated in several applications, showcasing the enabling potential of this platform for synthetic and medicinal chemistry.