In the presence of tetrabutylammonium decatungstate and chiral spiro phosphoric acid, a light-mediated asymmetric C–H functionalization of unactivated hydrocarbons with exocyclic enones has been established. A wide range of cycloalkanes, benzylic, and allylic hydrocarbons are tolerated. This protocol proceeds via a hydrogen atom transfer/radical addition/hydrogen abstraction/enantioselective protonation relay process.

Asymmetric functionalization of inert C­(sp3)–H bonds is a straightforward approach to realize versatile bond-forming events, allowing the precise assembly of molecular complexity with minimal functional manipulations. Here, we describe an asymmetric photocatalytic C­(sp3)–H bond addition to α-substituted acrylates by using tetrabutylammonium decatungstate (TBADT) as a hydrogen atom transfer (HAT) photocatalyst and chiral phosphoric acid as a chiral proton-transfer shuttle. This protocol is supposed to occur via a radical/ionic relay process, including a TBADT-mediated HAT to cleave the inert C­(sp3)–H bond, a 1,4-radical addition, a back hydrogen abstraction, and an enantioselective protonation. A variety of inert C–H bond patterns and α-substituted acrylates are well tolerated to enable the rapid synthesis of enantioenriched α-stereogenic esters from simple raw materials.

Asymmetric functionalization of the C­(sp3)–H bond is an attractive yet challenging strategy to achieve versatile bond-forming events, enabling the precise assembly of molecular complexity with minimal manipulation of functional groups. Here, we report an asymmetric C­(sp3)–H/C­(sp3)–H umpolung coupling of N-allylimine and coordinating α-aryl carbonyls by using chiral phosphoramidite-palladium catalysis. A wide variety of α-heteroaryl ketones and 2-acylimidazoles are nicely tolerated to open a convenient and tunable avenue for efficient synthesis of enantioenriched β-amino-γ,δ-unsaturated carbonyl derivatives with high levels of regio- and stereoselectivities, capable of providing a key intermediate for asymmetric synthesis of Focalin. This protocol showcases an umpolung reactivity of the N-allylimines through a concerted proton and two-electron transfer process to cleave the allylic C–H bond, effectively complementing established methodology for allylic C–H functionalization. An inner-sphere allylation pathway for both α-heteroaryl carbonyls and 2-acylimidazoles to attack the π-allylpalladium species is suggested by computational studies and experimental facts, wherein the nitrogen coordination to the palladium center enables the preference of branched regioselectivity.

Asymmetric functionalization of alkenes represents one of the most attractive and straightforward methods to achieve precise assembly of molecular complexity from cost-effectiveness and sustainability viewpoints. Although the regio-and enantioselective transformations on the carbon-carbon double bond of alkenes have been extensively studied, those on the allylic C−H bonds of inactivated alkenes remain to be explored. Here, we report a Pd-catalyzed branch-and enantioselective allylic C−H alkylation, capable of accommodating almost all types of α-alkenes that range from feedstocks annually manufactured on million-ton scale to ole ns tethering a wide scope of appended functionalities, providing unconventional access to chiral γ,δ-unsaturated amides. Notably, mechanistic studies reveal that the regioselectivity is not only governed by the coordination pattern of nucleophiles but also regulated by the ligational behaviors of ligands, highlighting the importance of the mono-ligation of chiral phosphoramidite ligands in provoking high levels of stereo-and branch-selectivity via a nucleophile-coordination enabled innersphere allylation pathway.