Enantioconvergent Indole Alkylation Using Diols via Oxocarbenium Intermediate by Borrowing Hydrogen To Access γ-/δ-Chiral Ketones

The asymmetric synthesis of chiral carbonyl compounds bearing remote stereocenters remains an attractive, yet challenging, goal in modern chemical synthesis. Herein, we report an enantioconvergent approach to γ- and δ-chiral ketones from simple racemic diols through a formal indole alkylation mediated by borrowing hydrogen catalysis. Mechanistic investigations revealed the involvement of a transient oxocarbenium intermediate that plays a key role in the transformation. The development of a new class of iridacycle catalysts featuring a chiral pyrroline backbone proved to be essential for achieving high levels of enantioselectivity. This cascade catalysis process proceeds without stoichiometric reagents and enables the efficient synthesis of a broad range of γ- and δ-chiral ketones in high yields and enantiopurity.