Iridium‐Catalyzed Reductive Deoxygenation of Esters for the Synthesis of Sterically Hindered Ethers

The synthesis of sterically hindered α‐tertiary and β‐quaternary (neopentylic) ethers has long been constrained by the limitations of traditional SN2 and related SN1 approaches, namely low or inexistent reactivity arising from severe steric hindrance or competitive elimination/rearrangement pathways diverting the reaction outcome. Herein, we describe a general solution to the synthesis of sterically hindered ethers via an iridium‐catalyzed reductive deoxygenation reaction of readily available ester and lactone starting materials. Employing commercially available, bench‐stable IrCl(CO)(P[OCH(CF3)2]3)2 as a precatalyst at 1 mol% loading with 4 equivalents of tetramethyldisiloxane (TMDS) as the terminal reductant at room temperature, this practical synthetic approach to hindered ethers features a simple, mix‐and‐stir, single‐vessel protocol under ambient conditions and produces a diverse range of both acyclic and cyclic ether products in good to excellent yields. Control experiments demonstrated that the IrCl(CO)(P[OCH(CF3)2]3)2/TMDS catalytic system could not only rapidly hydrosilylate esters to mixed silyl/alkyl hemiacetal intermediates but also catalyze the reduction of acetals directly to ethers, revealing the Lewis acidic and hydridic properties required for this deoxygenative transformation.