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 S_N2 and related S_N1 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.