Catalytic σ-Bond Annulation with Ambiphilic Organohalides Enabled by β-X Elimination.

Abstract

We describe a catalytic cascade sequence involving directed C(sp3)-H activation followed by β-heteroatom elimination to generate a PdII(π-alkene) intermediate which then undergoes redox-neutral annulation with an ambiphilic aryl halide to access 5- and 6-membered (hetero)cycles. Various alkyl C(sp3)-oxygen, nitrogen, and sulfur bonds can be selectively activated, and the annulation proceeds with high diastereoselectivity. The method enables modification of amino acids with good retention of enantiomeric excess, as well as σ-bond ring-opening/ring-closing transfiguration with low-strain heterocycles. Despite the mechanistic complexity of this transformation, the method employs simple conditions and is operationally straightforward to perform.