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We report a light-promoted hydroselenation of alkenes with high anti-Markovnikov selectivity. Mechanistic studies reveal a β-selenium effect, which imparts high anti-selectivity for radical addition through delocalization of a HAT transition state. 

Tandem catalysis enables the rapid construction of complex architectures from simple building blocks. This Perspective shares our interest in combining stereoselective hydrogenation with transformations such as isomerization, oxidation, and epimerization to solve diverse challenges. We highlight the use of tandem hydrogenation for preparing complex natural products from simple prochiral building blocks and present tandem catalysis involving transfer hydrogenation and dynamic kinetic resolution. Finally, we underline recent breakthroughs and opportunities for asymmetric hydrogenation. 

Conspectus By using transition metal catalysts, chemists have altered the “logic of chemical synthesis” by enabling the functionalization of carbon–hydrogen bonds, which have traditionally been considered inert. Within this framework, our laboratory has been fascinated by the potential for aldehyde C–H bond activation. Our approach focused on generating acyl-metal-hydrides by oxidative addition of the formyl C–H bond, which is an elementary step first validated by Tsuji in 1965. In this Account, we review our efforts to overcome limitations in hydroacylation. Initial studies resulted in new variants of hydroacylation and ultimately spurred the development of related transformations (e.g., carboacylation, cycloisomerization, and transfer hydroformylation). Sakai and co-workers demonstrated the first hydroacylation of olefins when they reported that 4-pentenals cyclized to cyclopentanones, using stoichiometric amounts of Wilkinson’s catalyst. This discovery sparked significant interest in hydroacylation, especially for the enantioselective and catalytic construction of cyclopentanones. Our research focused on expanding the asymmetric variants to access medium-sized rings (e.g., seven- and eight-membered rings). In addition, we achieved selective intermolecular couplings by incorporating directing groups onto the olefin partner. Along the way, we identified Rh and Co catalysts that transform dienyl aldehydes into a variety of unique carbocycles, such as cyclopentanones, bicyclic ketones, cyclohexenyl aldehydes, and cyclobutanones. Building on the insights gained from olefin hydroacylation, we demonstrated the first highly enantioselective hydroacylation of carbonyls. For example, we demonstrated that ketoaldehydes can cyclize to form lactones with high regio- and enantioselectivity. Following these reports, we reported the first intermolecular example that occurs with high stereocontrol. Ketoamides undergo intermolecular carbonyl hydroacylation to furnish α-acyloxyamides that contain a depsipeptide linkage. Finally, we describe how the key acyl-metal-hydride species can be diverted to achieve a C–C bond-cleaving process. Transfer hydroformylation enables the preparation of olefins from aldehydes by a dehomologation mechanism. Release of ring strain in the olefin acceptor offers a driving force for the isodesmic transfer of CO and H2. Mechanistic studies suggest that the counterion serves as a proton-shuttle to enable transfer hydroformylation. Collectively, our studies showcase how transition metal catalysis can transform a common functional group, in this case aldehydes, into structurally distinct motifs. Fine-tuning the coordination sphere of an acyl-metal-hydride species can promote C–C and C–O bond-forming reactions, as well as C–C bond-cleaving processes. 

In this article, we advance Rh-catalyzed hydrothiolation through the divergent reactivity of cyclopropenes. Cyclopropenes undergo hydrothiolation to provide cyclopropyl sulfides or allylic sulfides. The choice of bisphosphine ligand dictates whether the pathway involves ring-retention or ring-opening. Mechanistic studies reveal the origin for this switchable selectivity. Our results suggest the two pathways share a common cyclopropyl-Rh(III) intermediate. Electron-rich Josiphos ligands promote direct reductive elimination from this intermediate to afford cyclopropyl sulfides in high enantio- and diastereoselectivities. Alternatively, atropisomeric ligands (such as DTBM-BINAP) enable ring-opening from the cyclopropyl-Rh(III) intermediate to generate allylic sulfides with high enantio- and regiocontrol. 

Abstract We describe a copper catalyst that promotes the addition of phosphines to cyclopropenes at ambient temperature. A range of cyclopropylphosphines bearing different steric and electronic properties can now be accessed in high yields and enantioselectivities. Enrichment of phosphorus stereocenters is also demonstrated via a Dynamic Kinetic Asymmetric Transformation (DyKAT) process. A combined experimental and theoretical mechanistic study supports an elementary step featuring insertion of a Cu^I‐phosphido into a carbon‐carbon double bond. Density functional theory calculations reveal migratory insertion as the rate‐ and stereo‐determining step, followed by asyn‐protodemetalation.