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Updated: Oct 9, 2026

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
Orthogonal nucleophile-ordered assembly for modular access to enantiopure 1,2-amino alcohols
Mengfu Dai1, Tingrui Liu2, Mengmeng Zhang1
1State Key Laboratory of Microbial Technology, Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China.
Abstract:
The programmed assembly of multiple common chemicals with minimal reactivity differences into complex chiral architectures with high selectivity is a long-standing challenge in synthetic chemistry. Here we report a palladium-catalysed orthogonal multicomponent strategy that enables the sequential incorporation of two native N-H/O-H nucleophiles with similar reactivity into propargylic carbonates through a nucleophile-ordered assembly. Leveraging the tandem reactivity of the propargyl-palladium complex, this system functions as a sorting mechanism: stronger nucleophiles undergo outer-sphere addition to the propargyl-palladium intermediate, while weaker nucleophiles, guided by superior coordinating affinity, selectively attack the resulting allyl-palladium species through an inner-sphere mechanism. This strategy enables the precise recognition and ordered incorporation of diverse native nucleophile pairs, providing a platform and modular access to valuable chiral 1,2-amino alcohols and 1,2-diols with exceptional regio-, chemo-, Z- and enantiocontrol. This work demonstrates how subtle reactivity differences can be systematically harnessed for programmable complex synthesis from fundamental feedstocks.
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