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Updated: Jun 7, 2025

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
Pd/Cu-Cocatalyzed Asymmetric Cascade Heck/Tsuji-Trost Reaction to Access Non-natural Tryptophans
Panpan Li1, Yang Zhang2, Zijiao Liu1
1Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
Abstract:
A Pd-catalyzed asymmetric Heck cascade reaction involving the intramolecular carbopalladation of unsaturated hydrocarbons, followed by nucleophilic trapping of the resulting palladium species, is a powerful approach for constructing chiral N-heterocycles. However, the use of prochiral nucleophiles in these reactions remains significantly underexplored. Herein, we report a novel Pd/Cu catalytic system for the asymmetric cascade Heck/Tsuji-Trost reaction of allenamides and aldimine esters. This robust method allows for the rapid synthesis of a wide range of enantiopure non-natural α-substituted tryptophans in high yields (up to 99% yield) with excellent enantioselectivities (up to 98% ee). Additionally, the synthetic utility of this protocol is demonstrated through scale-up experiments and diverse valuable transformations.
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