Access to dialkylated allylic stereogenic centers by Ni-catalysed enantioselective hydrovinylation of unactivated alkenes

Abstract

Tertiary dialkylated allylic stereogenic centers are widespread substructures in bioactive molecules and natural products. However, enantioselective access to dialkyl substituted allylic motifs remains a long-term challenge. Herein, a straightforward protocol...

NiH-Catalyzed Regio- and Enantioselective Hydroalkylation for the Synthesis of β- or γ-Branched Chiral Aromatic N-Heterocycles

“…Recently, nickel hydride (Ni–H)-catalyzed reductive hydrocarbonations have provided a valuable synthetic platform for converting prochiral alkenes into a series of aryl-, vinyl-, and alkyl-substituted chiral amides, ester, organoboron derivatives, etc. , through the assistance of the preinstalled directing groups on the substrates, thus facilitating enantioselective reductive C­(sp 3 )–C­(sp 3 ) bond formation. − However, the relative Ni–H-catalyzed asymmetric transformations using the N atom of 2-substituted azaarenes as directing group have been rarely reported, possibly owing to several challenges. First, the strong chelating ability of the N atom in azaarene substrates with metal Ni species can compete with the N atom in the chiral ligands, such as bisoxazolines generally applied in asymmetric hydroalkylation transformations; Second, under transition metal-catalyzed reaction conditions, the reaction at the activated benzylated position is generally competitive, resulting in dominant α-position products and suppressing the asymmetric transformations at other positions owing to the adverse electronic effect; a, Third, Ni-catalyzed chain walking of substituted arenes has been a general synthetic approach toward proximal-selective hydroalkylation, thus interfering with the construction of the distal stereogenic center; ,− , Finally, excellent regio- and enantioselectivity was achieved simultaneously using unsymmetrical internal alkenes as substrates, avoiding some undesired side-reactions, such as the reversible transformation of the resulting alkyl–metal intermediates and the double-bond isomerized hydroalkylation through the chain-walking process .…”

Nickel‐Catalyzed Kinetic Resolution of Racemic Unactivated Alkenes via Enantio‐, Diastereo‐, and Regioselective Hydroamination

“…However, subjecting a racemic α‐substituted olefin to this method typically would lead to undesired mixtures if any of the three selectivities are not controlled. For instance, diastereo‐ and regioselective strategies may result in a racemic mixture of syn ‐ or anti ‐products, [45] while enantio‐ and regioselective approaches may produce a nearly equimolar mixture of diastereomers [46] . Therefore, there is an urgent need to develop a new protocol that can control all three selectivities, enabling access to multiple stereocenters in a single step (Scheme 1b).…”

Regioselective Hydroalkylation of Vinyl- and Allylsilanes as Well as Vinylgermanes under Ni–H Catalysis

“…To overcome these drawbacks, the promising field of metal-catalyzed hydrocarbonation of alkenes has witnessed a rapid development in recent years . The key examples include alkene hydroarylation/hydroalkenylation and hydroalkylation , reactions. Nickel rather than copper and palladium catalysis has proven to be particularly effective for hydrocarbonation with unactivated alkyl electrophiles. , The addition of an assumed Ni–H complex across terminal alkenes typically favors the linear regioisomer, while an aryl ,,, or boryl ,, substituent steers the nickel center to its benzylic or α-position.…”