Modular Synthesis of Chiral 1,3-Diboronates with Differentiable Boryl Groups via Cu-Catalyzed Borylalkylation of Styrenes

A practical, modular approach for the preparation of enantioenriched 1,3-diboronates with differentiable boron moieties (Bdan vs Bpin) is introduced. The reaction involves borylcupration of the alkene, followed by capture of the catalytically generated alkylcopper intermediate with commercially available ICH 2 Bpin to synthetically valuable 1,3-bis(boryl)alkanes. The newly developed NHC-copper catalyst is the significant parameter for the reactions, which enables to produce a wide range of chiral 1,3-diboronates in high reactivities and enantioselectivities. Furthermore, a variety of chiral building blocks could be easily accessed through chemoselective functionalization of two boron groups in a stepwise manner. The utility of this reaction was further highlighted by the efficient synthesis of the chiral precursor of Glabridin analogue. DFT calculation profiles demonstrated that after the stereoselective borylcupration, the alkylation step takes place through an S N 2-type oxidative addition mechanism of ICH 2 Bpin followed by a reductive elimination.