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.