Catalytic -Bond Annulation with Ambiphilic Organohalides Enabled by -X Elimination

We describe a catalytic cascade sequence involving directed C(sp(3))-H activation followed by & beta;-heteroatom elimination to generate a Pd-II(& pi;-alkene) intermediate that then undergoes redox-neutral annulation with an ambiphilic aryl halide to access 5- and 6-membered (hetero)cycles. Various alkyl C(sp(3))-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 & sigma;-bond ring-opening/ring-closing transfiguration of low-strain heterocycles. Despite its mechanistic complexity, the method employs simple conditions and is operationally straightforward to perform.