Chemodivergent Tandem Hydroalkylation and Hydroalkenoxylation of Conjugated Enynes
Bo‐Yuan Xie, Zhi‐Tao He
Abstract
Due to the instability and weak O-nucleophilicity of enol, carbonyl compounds prefer to function as C-nucleophiles instead of O-nucleophiles in the extensively studied transition metal-catalyzed hydrofunctionalizations of unsaturated bonds. The corresponding hydroalkenoxylation reaction has thus long been unexplored. Here, we describe a chemodivergent protocol for the challenging hydroalkenoxylation reactions. Dictated by the Pd catalyst bearing different ligands, both 5- exo-trig and 6- endo-trig hydroalkenoxylation processes are demonstrated to be feasible between the reaction of 1,3-enynes and ketoesters, and polysubstituted hydrofurans and hydropyrans are achieved in good yields and excellent chemoselectivities. In addition, the enantioselective hydroalkenoxylation reaction is also explored under an Rh catalyst in moderate efficiency but with high stereoselectivities. Mechanistic studies corroborate the designed tandem hydroalkylation and hydroalkenoxylation processes and uncover that a ligand-to-ligand hydrogen transfer process might be involved as the turnover-limiting step in the 5- exo-trig hydroalkenoxylation.