具有生物活性的C(2)手性-4-色满酮衍生物的不对称合成研究进展

doi:10.6023/cjoc202601039

摘要/Abstract

C(2)手性-4-色满酮因具有显著的生物活性而备受关注. 有关C(2)手性-4-色满酮衍生物的不对称合成已成为有机合成领域的研究热点之一, 其中以色烯酮为底物, 通过C(2)=C(3)双键的不对称加成得到C(2)手性-4-色满酮衍生物, 因前体化合物易得、立体选择性强及原子经济性高等优点, 成为此类衍生物合成的主要途径之一. 综述了近十年此类合成方法, 主要介绍了通过金属手性配合物参与的不对称催化. 对比分析不同催化体系下立体选择性的反应机理, 归纳总结了有利于提高立体选择性的催化体系结构特点, 并对此领域当前面临的挑战和未来发展方向进行了展望.

关键词: 生物活性, 色烯酮, 不对称合成, 金属手性配合物, 色满酮

C(2) chiral-4-chromanones have attracted considerable attention owing to their pronounced biological activities. The asymmetric synthesis of C(2) chiral-4-chromanone derivatives has therefore emerged as an important research topic in the field of organic synthesis. Among the various strategies, the use of chromenone as the substrate to obtain C(2) chiral-4-chro- manone derivatives through asymmetric addition of C(2)=C(3) double bond has become one of the main routes for the synthesis of such derivatives due to the advantages of ready availability of the substrates, high stereoselectivity, and excellent atom economy. The synthetic methodology over the past decade is summarized with a focus on asymmetric catalysis mediated by chiral metal complexes. A comparative analysis of the stereoselective mechanisms under different catalytic systems is provided, the structural features of catalytic systems that are beneficial for enhancing stereoselectivity are summarized, and the current challenges and future perspectives in this field are discussed.

Key words: biological activity, chromenone, asymmetric synthesis, chiral metal complex, chromanone

引用此文

王桂霞, 龚木兰, 杜金龙, 程啟明, 苗力文, 孔翔飞. 具有生物活性的C(2)手性-4-色满酮衍生物的不对称合成研究进展[J]. 有机化学, 2026, 46(8): 2949-2968.

Guixia Wang, Mulan Gong, Jinlong Du, Qiming Cheng, Liwen Miao, Xiangfei Kong. Progress in the Asymmetric Synthesis of C(2) Chiral-4-chromanone Derivatives with Bioactivities[J]. Chinese Journal of Organic Chemistry, 2026, 46(8): 2949-2968.

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图/表 30

图1. 典型的C(2)手性-4-色满酮衍生物的分子结构

Figure 1. Molecular structures of representative C(2) chiral-4-chromanone derivatives

图式1. 借助C(2)手性-4-色满酮合成(＋)-gonytolide A

Scheme 1. Synthesis of (＋)-gonytolide A via C(2) chiral-4-chromanone derivatives

图式2. C(2)手性-4-色满酮衍生物的不对称合成方法

Scheme 2. Asymmetric synthetic methods for C(2) chiral-4-chromanone derivatives

图式3. Cu(OAc)2/(R)-DM-Segphos手性配合物催化不对称加成

Scheme 3. Cu(OAc)2/(R)-DM-Segphos chiral complex-catalyzed asymmetric addition

图式4. CuI/(S)-StackPhos手性配合物催化不对称加成

Scheme 4. CuI/(S)-StackPhos chiral complex-catalyzed asymmetric addition

图式5. CuI/(R)-BINOL-PA手性配合物催化不对称加成

Scheme 5. CuI/(R)-BINOL-PA chiral complex-catalyzed asymmetric addition

图式6. CuI/(S)-Bn-Box手性配合物催化不对称加成

Scheme 6. CuI/(S)-Bn-Box chiral complex-catalyzed asymmetric addition

图式7. 不同取代基的双噁唑啉配体对产物构型的影响

Scheme 7. Effect of bis(oxazoline) ligands with different substituents on the configuration of products

图式8. [Cu(CH3CN)4]PF6/(R)-BIPHEP-type手性配合物催化不对称加成

Scheme 8. [Cu(CH3CN)4]PF6/(R)-BIPHEP-type chiral complex-catalyzed asymmetric addition

图式9. 不同Cu手性配合物对C(2)-甲酸甲酯基-色烯酮立体选择性的影响

Scheme 9. Effect of various chiral Cu complexes on the stereoselectivity of C(2)-methoxycarbonyl chromenones

图式10. 硼酸酯促进的Cu手性配合物催化不对称加成

Scheme 10. Asymmetric addition catalyzed by chiral Cu complexes promoted by borate esters

图式11. CuCl/Bn-FOXAP手性配合物催化不对称加成

Scheme 11. CuCl/Bn-FOXAP chiral complex-catalyzed asymmetric addition

图式12. Pd(OTf)2/BCO-Phen手性配合物催化不对称加成

Scheme 12. Pd(OTf)2/BCO-Phen chiral complex-catalyzed asymmetric addition

图式13. Pd(TFA)2/PyDHIQ手性配合物催化不对称加成

Scheme 13. Pd(TFA)2/PyDHIQ chiral complex-catalyzed asymmetric addition

图式14. (Pd2(dba)3)•CHCl3/(S,R,R)-Phosphoramidite手性配合物催化不对称加成

Scheme 14. (Pd2(dba)3)•CHCl3/(S,R,R)-Phosphoramidite chiral complex-catalyzed asymmetric addition

图式15. Pd(TFA)2/t-Bu-CarOx手性配合物催化不对称加成

Scheme 15. Pd(TFA)2/t-Bu-CarOx chiral complex-catalyzed asymmetric addition

图式16. Pd(TFA)2/t-Bu-NHPyOx手性配合物催化不对称加成

Scheme 16. Pd(TFA)2/t-Bu-NHPyOx chiral complex-catalyzed asymmetric addition

图式17. [RhCl(C2H4)2]2/(R,R)-Ph-bod*手性配合物催化不对称加成

Scheme 17. [RhCl(C2H4)2]2/(R,R)-Ph-bod* chiral complex-cata- lyzed asymmetric addition

图式18. [Rh(NBD)2]BF4/SL-J216-1手性配合物催化不对称加成

Scheme 18. [Rh(NBD)2]BF4/SL-J216-1 chiral complex-catalyzed asymmetric addition

图式19. [Rh(COD)Cl]2/(R,R)-f-SpiroPhos手性配合物催化不对称加成

Scheme 19. [Rh(COD)Cl]2/(R,R)-f-SpiroPhos chiral complex-catalyzed asymmetric addition

图式20. RuCl2(PPh3)3/(S,Sp)-RuPHOX手性配合物催化不对称加成

Scheme 20. RuCl2(PPh3)3/(S,Sp)-RuPHOX chiral complex-catalyzed asymmetric addition

图式21. (S,S)-Zn-ProPhenol手性配合物催化不对称加成

Scheme 21. (S,S)-Zn-ProPhenol chiral complex-catalyzed asymmetric addition

图式22. Sc(OTf)3/L3-PrEt2手性配合物催化不对称加成

Scheme 22. Sc(OTf)3/L3-PrEt2 chiral complex-catalyzed asymmetric addition

图式23. 光/Sc手性配合物协同催化不对称加成

Scheme 23. Asymmetric addition enabled by cooperative photoredox/Sc chiral complex catalysis

图式24. LiAlH4/(R)-BINOL手性配合物催化不对称加成

Scheme 24. LiAlH4/(R)-BINOL chiral complex-catalyzed asymmetric addition

图式25. Ce(OTf)3/L3-PrMe2手性配合物催化不对称加成

Scheme 25. Ce(OTf)3/L3-PrMe2 chiral complex-catalyzed asymmetric addition

图式26. 奎宁-方酰胺双功能有机催化剂

Scheme 26. Quinine-squaramide bifunctional organocatalyst

图式27. CPA介导质子-电子协同转移催化

Scheme 27. CPA-mediated proton-coupled electron transfer (PCET) catalysis

图式28. 光催化色烯酮的二聚反应

Scheme 28. Photocatalytic dimerization of chromenone

图式29. 四三唑螺旋催化剂

Scheme 29. Helical tetratriazole catalyst

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