Ligand Controlled Stereodivergent Construction of 1,3-Nonadjacent Stereocenters via Nickel-Catalyzed Reductive Cyclization/Cross-Couplings

Molecules with multiple stereocenters are widely present in biologically active natural products and pharmaceuticals.These molecules exhibit great three-dimensional structural diversity, which can affect the strength and selectivity of protein-ligand interactions [1] .Therefore, the precise synthesis of each stereoisomer is very important in medicinal chemistry.In the past 40 years, asymmetric catalysis has developed rapidly, and a variety of methods has been developed to construct chiral compounds containing single or adjacent stereocenters [2] .However, there are few reports on the simultaneous construction of 1, 3-nonadjacent stereocenters in a highly stereoselective manner, especially in acyclic compounds [3] (Fig. 1(a)).In addition, for the stereodivergent synthesis of all possible stereoisomers of the product, most of the studies to date has focused on dual-catalyst systems, while it reamins extremely challenging to achieve such transformations using a single catalyst by adjusting the chiral ligand [4] .The Kong group has been focusing on nickel-catalyzed reductive cyclization and difunctionalization of alkenes to efficiently construct heterocycles containing all-carbon quaternary stereocenters.This transformation has attracted widespread attention due to its advantages in cases where C(sp 3 ) electrophiles are unstable or require multiple steps to prepare [5] .Although a variety of electrophiles have been explored, methods for constructing 1,3-nonadjacent stereocenters using secondary alkyl electrophiles have not been developed and remain a formidable challenge.