Pd/Cu-Cocatalyzed\nAsymmetric Cascade Heck/Tsuji–Trost\nReaction to Access Non-natural Tryptophans

A Pd-catalyzed asymmetric Heck cascade reaction involving\nthe intramolecular\ncarbopalladation of unsaturated hydrocarbons, followed by nucleophilic\ntrapping of the resulting palladium species, is a powerful approach\nfor constructing chiral <i>N</i>-heterocycles. However,\nthe use of prochiral nucleophiles in these reactions remains significantly\nunderexplored. Herein, we report a novel Pd/Cu catalytic system for\nthe asymmetric cascade Heck/Tsuji–Trost reaction of allenamides\nand aldimine esters. This robust method allows for the rapid synthesis\nof a wide range of enantiopure non-natural α-substituted tryptophans\nin high yields (up to 99% yield) with excellent enantioselectivities\n(up to 98% ee). Additionally, the synthetic utility of this protocol\nis demonstrated through scale-up experiments and diverse valuable\ntransformations.