Enantioselective Addition of Cyclic Ketones to Unactivated Alkenes Enabled by Amine/Pd(II) Cooperative Catalysis

Abstract

Amine/Pd(II) cooperative catalysis has enabled a highly enantioselective addition of cyclic ketones to unactivated alkenes. The hallmark of the strategy includes amide-directed, regioselective activation of alkenes by Pd(II) and enhancing the nucleophilicity of α-carbon of the ketones by enamine catalysis to synergistically drive the reaction, which is basically unable to be accessed by a single catalyst. The combination of a commercially available Pd(II) catalyst and diphenylprolinol was able to provide the γ-addition products with good to high yields and efficient stereochemical control (up to 95% ee).

Catalytic, Enantioselective α‐Alkylation of Azlactones with Nonconjugated Alkenes by Directed Nucleopalladation

“…However, nonconjugated alkenes have only been rarely employed as electrophiles despite their clear advantages over alkyl (pseudo)halides in terms of cost and availability . The use of nonconjugated alkenes and carbonyl pronucleophiles as reaction partners in a Wacker‐type manifold would represent a powerful approach towards enantioselective α‐alkylation, yet remains unknown to the best of our knowledge . The goal of the present study was to demonstrate this concept in the context of a synthetically significant problem, the α‐alkylation of masked amino acids to form α‐quaternary amino‐acid products (Scheme B).…”

Alkyl halides as both hydride and alkyl sources in catalytic regioselective reductive olefin hydroalkylation

“…1a). Of these cases, either a limited range of ureas 34 , organometallic reagents 35,36 or carbonyl compounds [37][38][39] were employed as nucleophiles, or an exogenous protic source 40 or hydrosilane/base reagent [41][42][43][44][45] is needed to (i) promote protodemetallation or (ii) generate the requisite metal-hydride species.…”

Metal‐Catalyzed Substrate‐Directed Enantioselective Functionalization of Unactivated Alkenes

“…The substrate‐directed nucleopalladation also provides the opportunity for creation for stereocenters at the carbon nucleophile. Zhang, Gong and co‐workers have developed a chiral amine/Pd(II) cooperative catalysis to realize a highly enantioselective addition of cyclic ketones to unactivated alkenes (Scheme ) . Substrate coordination to Pd(II) activates the alkenes, while enamine formation enhances the nucleophilicity of the α‐carbon of the ketones.…”