Ligand-Controlled Cobalt-Catalyzed Regio-, Enantio-, and Diastereoselective Oxyheterocyclic Alkene Hydroalkylation.

Metal-hydride-catalyzed alkene hydroalkylation has been developed as an efficient method for C(sp3)-C(sp3) coupling with broad substrate availability and high functional group compatibility. However, auxiliary groups, a conjugated group or a chelation-directing group, are commonly required to attain high regio- and enantioselectivities. Herein, we reported a ligand-controlled cobalt-hydride-catalyzed regio-, enantio-, and diastereoselective oxyheterocyclic alkene hydroalkylation without chelation-directing groups. This reaction enables the hydroalkylation of conjugated and unconjugated oxyheterocyclic alkenes to deliver C2- or C3-alkylated tetrahydrofuran or tetrahydropyran in uniformly good yields and with high regio- and enantioselectivities. In addition, hydroalkylation of C2-substituted 2,5-dihydrofuran resulted in the simultaneous construction of 1,3-distereocenters, providing convenient access to polysubstituted tetrahydrofuran with multiple enantioenriched C(sp3) centers.

Nickel-Catalyzed Remote Asymmetric Hydroalkylation of Alkenyl Ethers to Access Ethers of Chiral Dialkyl Carbinols.

Site- and enantio-selective alkyl-alkyl bond formation is privileged in the retrosynthetic analysis due to the universality of sp3-hybridized carbon atoms in organic molecules. Herein, we report a nickel-catalyzed remote asymmetric hydroalkylation of alkenyl ethers via synchronous implementation of alkene isomerization and enantioselective C(sp3)-C(sp3) bond formation. Regression analysis of catalyst structure-activity relationships accelerates the rational ligand modification through modular regulation. This reaction has several advantages for synthesizing chiral dialkyl carbinols and their ether derivatives, including the broad substrate scope, good functional group tolerance, excellent regioselectivity (>20:1 regioisomeric ratio), and high enantioselectivity (up to 95% enantiomeric excess).

Ligand-Controlled Cobalt-Catalyzed Regiodivergent Alkyne Hydroalkylation.

Regiodivergent alkyne hydroalkylation to generate different isomers of an alkene from the same alkyne starting material would be beneficial; however, it remains a challenge. Herein, we report a ligand-controlled cobalt-catalyzed regiodivergent alkyne hydroalkylation. The sensible selection of bisoxazoline (L1) and pyridine-oxazoline (L8) ligands led to reliable and predictable protocols that provided (E)-1,2-disubstituted and 1,1-disubstituted alkenes with high E/Z stereoselectivity and regioisomeric ratio starting from identical terminal alkyne and alkyl halide substrates and produced trisubstituted alkenes in the case of internal alkynes. This method exhibits a broad scope for terminal and internal alkynes with a wide range of activated and unactivated alkyl halides and shows excellent functional group compatibility.