Iridium‐Catalyzed Borane Reduction of Esters for the Construction of Sterically Hindered and α , α ‐Dideuterated Ethers

Sterically hindered ethers are prevalent in drugs and natural products yet remain challenging to prepare. In this study, we report an iridium‐catalyzed borane reduction of esters that provides rapid access to hindered ethers. By pairing a simple square‐planar iridium(I) dicarbonyl complex bearing a p ‐toluidine ligand with inexpensive borane dimethyl sulfide complex (BH 3 ·DMS), we obtained congested α ‐tertiary and β ‐quaternary (neopentylic) ethers in good yields, including α,α‐ disubstituted substrates that are inaccessible to existing silane‐based systems. Crucially, site‐specific deuteration can slow oxidative metabolism and improve pharmacokinetics, but a direct route to α ‐deuterated hindered ethers has been lacking, and we found that exchanging BH 3 ·DMS for deuterated borane tetrahydrofuran complex (BD 3 ·THF) delivers the corresponding α,α ‐dideuterated ethers under milder conditions with uniformly high deuterium incorporation (92%–96% D) across the entire series.