α,α-二氟-β-氨基膦酸酯的合成与应用研究进展

doi:10.6023/cjoc202405013

摘要/Abstract

α,α-二氟-β-氨基膦酸酯因含有一个氨基基团, 可以作为氨基酸的类似物, 在生物化学领域引起了广泛的研究兴趣. 更重要的是, 这类化合物还是非常高效的有机合成中间体, 其在二氟膦酸酯衍生物的合成方面有非常重要的应用. 因此, α,α-二氟-β-氨基膦酸酯的合成和应用是磷化学领域的研究热点. 系统全面地总结了近些年有关α,α-二氟-β-氨基膦酸酯的研究进展, 讨论了α,α-二氟-β-氨基膦酸酯的合成及其相关的反应, 以期为二氟膦酸酯衍生物的合成研究提供一定的参考.

关键词: 二氟甲基膦酸酯, α,α-二氟-β-氨基膦酸酯, 卡宾, 重氮, 胺, 生物活性化合物

α,α-Difluoro-β-aminophosphonates can be looked as structural analogies with α-amino acids, which have attracted great attention in biological and medicinal chemistry during the past decades. Furthermore, these compounds also belong to an important type of organic building blocks for the rapid synthesis of difluoromethylenephosphonate-containing molecules. Thus, the preparation and application of α,α-difluoro-β-aminophosphonates are hot research topics in organic phosphine chemistry. A comprehensive summary of the literature reports related to α,α-difluoro-β-aminophosphonates in recent years is presented. And aspects of synthesis and applications of α,α-difluoro-β-aminophosphonates are discussed, in order to provide critical guidance for the further development of reactions and applications for the synthesis of difluoromethylenephosphonate derivatives.

Key words: aminophosphonate, α,α-difluoro-β-aminophosphonate, carbene, diazo compound, amine, bioactive compound

引用此文

杜友龙, 王倩, 梅海波, Romana Pajkert, Gerd-Volker Röschenthaler, 韩建林. α,α-二氟-β-氨基膦酸酯的合成与应用研究进展[J]. 有机化学, 2024, 44(12): 3686-3701.

Youlong Du, Qian Wang, Haibo Mei, Romana Pajkert, Gerd-Volker Röschenthaler, Jianlin Han. Recent Advances on the Synthesis and Application of α,α-Difluoro-β-aminophosphonates[J]. Chinese Journal of Organic Chemistry, 2024, 44(12): 3686-3701.

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图/表 24

Figure 1. Examples of biologically active difluorinated aminophosphonates and phosphonic acids

Scheme 1. Synthetic route to 2-amino-1,1-difluorophosphonic acid

Scheme 2. General strategies for the synthesis of α,α-difluoro-β-aminophosphonates

Scheme 3. Classical synthetic routes to LiCF2P(O)(OR)2 and TMSCF2P(O)(OR)2

Scheme 4. Diastereoselective synthesis of α,α-difluoro-β-aminophosphonates

Scheme 5. Synthesis of N-protected α,α-difluoro-β-aminophosphonates

Scheme 6. Synthesis of N-phenyl α,α-difluoro-β-aminophosphonate

Scheme 7. Stereoselective synthesis of 1-C-phosphonodifluoromethyl iminosugars

Scheme 8. Addition of LiCF2P(O)(OEt)2 to furanosylamines

Scheme 9. Addition of TMSCF2P(O)(OEt)2 to benzylidene-methylimine

Scheme 10. Addition of TMSCF2P(O)(OEt)2 to selected ena- mines

Scheme 11. Addition of TMSCF2P(O)(OEt)2 to chiral N-tert- butanesulfinyl imines

Scheme 12. Difluorophosphorylation of tetrahydroisoquinoline

Scheme 13. Reaction of difluoromethylphosphonate imine with N-protected indoles

Scheme 14. Preparation of α,α-difluoro-β-aminophosphonates via reduction of α,α-difluoro-β-iminophosphonates

Scheme 15. Synthetic route to α,α-difluoro-β-aminophosphonates via reduction of α,α-difluoro-β-iminophosphonate

Scheme 16. Petasis boronic acid Mannich reaction of α,α-difluoro-β-aminophosphonates

Scheme 17. O—H insertion reaction of (β-diazo-α,α-difluoroethyl)phosphonates

Scheme 18. Application of in situ generated (β-diazo-α,α-difluoroethyl)phosphonates in [3＋2] cycloadditions

Scheme 19. Halogenation reaction of (β-diazo-α,α-difluoroeth- yl)phosphonates

Scheme 20. One-pot reaction of (β-amino-α,α-difluoroethyl)phosphonates via aza-Wittig reagent

Scheme 21. Possible mechanism for the aza-Wittig reaction of (β-amino-α,α-difluoroethyl)phosphonates

Scheme 22. Rh-catalyzed cascade carbonylation/C—F bond cleavage reaction of (β-diazo-α,α-difluoroethyl)phosphonates

Scheme 23. Ru-catalyzed reaction of (β-diazo-α,α-difluoroethyl)phosphonates with Hantzsch esters

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