Unnatural a- and g-amino acids display a diverse range of biological activities and serve as crucial intermediates in pharmaceutical production. Specifically, the synthesis of such molecules has been highly sought after in both academia and industry. Nevertheless, their direct synthesis from simple bulk feedstocks has remained largely unexplored, and the switchable synthesis of a- and g-amino acids through a shared intermediate has never been documented. We disclose herein a four-component reaction involving readily available bulk chemicals to facilitate the switchable synthesis of a- and g-amino acids from a shared extended p-quinone methide through a tailored amination strategy. A diverse array of amines, including several unmodified drug molecules, along with various other nucleophiles, are readily utilized as suitable substrates in this reaction. We believe this work could inspire future intensive efforts toward the switchable synthesis of amino acids in a practical and efficient manner.
Ref: Zhang, C.-G.; Tang, Y.-P.; Huang, Q.; Qiu, Y.-K.; Yan, H.& Dai, L. Tailored amination enables switchable synthesis of α- and γ-amino acid derivatives from extended quinone methides. Nat. Commun., 2025, 5683.
Representative Publications
*Corresponding author , §Co-first author
Awaiting next submission...
2025
18. Zhang, C.-G.; Tang, Y.-P.; Huang, Q.; Qiu, Y.-K.; Yan, H.* and Dai, L.* Tailored amination enables switchable synthesis of α- and γ-amino acid derivatives from extended quinone methides. Nature Communications, 2025, DOI : 10.1038/s41467-025-60749-7
2024
17. Huang, Q.; Tang, Y.-P.; Zhang, C.-G.; Wang, Z.* and Dai, L.* Enantioselective Synthesis of Helically Chiral Molecules Enabled by Asymmetric Organocatalysis. ACS Catalysis, 2024, 16256.
16. Zhang, Z and Dai, L.* Construction of axially chiral molecules enabled by photoinduced enantioselective reactions Chemical Science, 2024, 12636. This article is part of the themed collections: 2024 Chemical Science HOT Article Collection and 2024 Chemical Science Perspective & Review Collection
15. Dai, L.; Zhou, X.; Guo, J.; Huang, Q. and Lu, Y.* Copper-catalyzed atroposelective synthesis of C–O axially chiral compounds enabled by chiral 1,8-naphthyridine based ligands. Chemical Science, 2024, 5993.
14. Zhou, X.§; Huang, Q§; Guo, J.; Dai, L.* and Lu, Y.* Catalytic Asymmetric Construction of α,α-DiarylAldehydes via Oxo hydroarylation of Terminal Alkynes. Advanced Science, 2024, 202309645.
13. Dai, L.; Sun, Y.-L.; Guo, J.; Zhou, X.; Huang, Q. and Lu, Y.* Atroposelective Synthesis of 3-Aryl-indoles through a One-pot 2,3-Difunctionalization of Simple Indoles. CCS Chemistry, 2024, DOI: 10.31635/ccschem.023.202303434.
Before 2024
12. Dai, L.; Zhou, X.; Guo, J.; Dai X.; Huang, Q and Lu, Y.* Diastereo- and atroposelective synthesis of N-arylpyrroles enabled by light-induced phosphoric acid catalysis. Nature Communications, 2023, 4813.
11. Zhou, X.; Huang, Q; Guo, J.; Dai, L.* and Lu, Y.* Molecular editing of pyrroles via a skeletal recasting strategy. ACS Central Science, 2023, 1758-1767.
10. Zhou, X.§; Huang, Q§; Guo, J.; Dai, L.* and Lu, Y.* Enantioselective De Novo Synthesis of a,a-Diarylketones from Alkynes. Angew. Chem. Int. Ed., 2023, e202310078. (Highlighted by Prof. Trauner; Synfacts 2023, 19, 1268)
9. Dai, X.; Zhang, F.; Dai, L.* and Lu, Y.* Asymmetric Dearomatization of Electron-Deficient Heteroarenes by a Phosphine-Catalyzed [3+2] Annulation with Vinylcyclopropanes. CCS Chemistry, 2023, 5, 2023–2032.
8. Dai, L and Lu, Y.* Atroposelective remote meta-C-H arylation of 2-arylanilines. Chem, 2023, 1347-1349.
7. Dai, L.; Guo, J.; Huang, Q. and Lu, Y.* Asymmetric multifunctionalization of alkynes via photo-irradiated organocatalysis. Science Advances, 2022, 8, eadd2574.
6. Zhang, F.; Dai, X.; Dai, L.; Zheng, W.; Chan, W.-L.; Tang, X.; Zhang, X. and Lu, Y.* “Phosphine-Catalyzed Enantioselective (3+2) Annulation of Vinylcyclopropanes with Imines for the Synthesis of Chiral Pyrrolidines. Angew. Chem. Int. Ed., 2022, 61, e202203212.
5. Tan, C. X. A.; Li, R.; Zhang, F.; Dai, L.; Ullah, N.* and Lu, Y.* “Synthesis of axially chiral CF3-substituted 2-arylpyrroles by sequential phosphine-catalysed asymmetric [3+2] annulation and oxidative central-to-axial chirality transfer. Angew. Chem. Int. Ed., 2022, 61, e202209494.
4. Huang, Q.; Chen, Y.; Zhou, X.; Dai, L. and Lu, Y.* “Nickel-hydride-catalyzed diastereo- and enantioselective hydroalkylation of cyclopropenes. Angew. Chem. Int. Ed., 2022, 61, e202210560.
3. Dai, L. and Ye, S.*, NHC-catalyzed ε-umpolung via p-quinodimethanes and its nucleophilic addition to ketones. ACS Catalysis, 2020, 10, 994-998. (Highlighted by Prof. B. List; Synfacts 2020, 16, 0458)
2. Dai, L.; Qiu, Y.; Xu, Y.Y. and Ye, S.*, Biomass transformation of cellulose via N-heterocyclic carbene-catalyzed umpolung of 5-(chloromethyl) furfural. Cell Reports Physical Science, 2020, 1, 100071.
1. Dai, L.; Xia, Z.H.; Gao, Y.Y.; Gao, Z.H.* and Ye, S.*, Visible-Light-Driven N-Heterocyclic Carbene Catalyzed γ- and e-Alkylation with Alkyl Radicals. Angew. Chem. Int. Ed., 2019, 58, 18124-18130.
