An efficient Co III -catalyzed three-component strategy to prepare homoallylic alcohols containing acyclic quaternary centers is disclosed. This transformation enables the introduction of two CÀC s bonds through CÀHb ond activation and sequential addition to internally substituted dienes and aw ide range of aldehydes and activated ketones. Isoprene and other internally monosubstituted dienes are effective inputs,w ith the reaction proceeding with high diastereoselectivity for those substrate combinations that result in more than one stereogenic center.M oreover,t he opposite relative stereochemistry can be achieved by employing 1,2-disubstituted dienes.Amechanism for the transformation is proposed based upon the relative stereochemistry of the products and studies with isotopically labeled starting materials.

We report a combined photocatalytic and hydrogen atom transfer (HAT) approach for the light-mediated epimerization of readily accessible piperidines to provide the more stable diastereomer with high selectivity. The generality of the transformation was explored for a large variety of di-to tetrasubstituted piperidines with aryl, alkyl, and carboxylic acid derivatives at multiple different sites. Piperidines without substitution on nitrogen as well as N-alkyl and aryl derivatives were effective epimerization substrates. The observed diastereoselectivities correlate with the calculated relative stabilities of the isomers. Demonstration of reaction reversibility, luminescence quenching, deuterium labeling studies, and quantum yield measurements provide information about the mechanism.

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We report a photocatalyzed epimerization of morpholines and piperazines that proceeds by reversible hydrogen atom transfer (HAT) and provides an efficient strategy for editing the stereochemical configurations of these saturated nitrogen heterocycles, which are prevalent in drugs. More stable morpholine and piperazine isomers are obtained from the more synthetically accessible but less stable stereoisomers, and a broad scope is demonstrated in terms of substitution patterns and functional group compatibility. The observed distributions of diastereomers correlate well with the relative energies of the diastereomer pairs as determined by density functional theory (DFT) calculations. Mechanistic studies, including luminescence quenching, deuterium labeling reactions, and determination of reversibility support a thiyl radical-mediated HAT pathway for the epimerization of morpholines. Investigation of piperazine epimerization established that the mechanism is more complex and led to the development of thiol-free conditions for the highly stereoselective epimerization of N,N′-dialkyl piperazines for which a previously unrecognized radical chain HAT mechanism is proposed.