叔醇的动力学拆分研究进展

doi:10.6023/cjoc202110009

摘要/Abstract

手性叔醇结构广泛存在于生物活性物质、天然产物和药物分子中, 实现其高效不对称催化合成具有重要意义. 消旋醇的动力学拆分是一种合成高光学纯度手性醇的重要方法, 然而由于叔醇α-碳上带三个不同的非氢取代基团, 手性识别难度较大, 因而发展高效且具有广泛底物适用性的叔醇动力学拆分方法具有较大的挑战. 尽管如此, 近年来非酶催化的叔醇的动力学拆分领域取得了快速的发展, 一些新颖的不对称催化反应、催化体系被成功应用于叔醇的动力学拆分反应中. 对叔醇动力学拆分反应进行了系统总结, 分类介绍了这些反应的底物适用性、特点、机理以及局限等, 并对该领域的未来发展进行展望.

关键词: 手性叔醇, 不对称催化, 动力学拆分

Chiral tertiary alcohol is widely present in a series of bioactive compounds, natural products and pharmaceuticals. Consequently, the development of efficient asymmetric catalytic methods for their syntheses is highly important. Kinetic resolution (KR) is an important strategy to access enantioenriched alcohols from racemic alcohols. However, due to the requirement to distinguish three none-hydrogen substituents at the α-position of tertiary alcohols, it is challenging to develop highly efficient kinetic resolution protocols for tertiary alcohols with broad substrate scope. Nevertheless, significant progress has been made in the field of nonenzymatic kinetic resolution of tertiary alcohols in recent years, and a number of novel asymmetric reactions and catalytic systems have been successfully applied in the KR of tertiary alcohols. The tremendous advances in the kinetic resolution of tertiary alcohols are comprehensively reviewed, the substrate scope, characteristics, mechanisms and limitations of these methods are summarized, and our perspective on this research field is also provided.

Key words: chiral tertiary alcohols, asymmetric catalysis, kinetic resolution

引用此文

陈运荣, 刘炜, 杨晓瑜. 叔醇的动力学拆分研究进展[J]. 有机化学, 2022, 42(3): 679-697.

Yunrong Chen, Wei Liu, Xiaoyu Yang. Recent Advances in Kinetic Resolution of Tertiary Alcohols[J]. Chinese Journal of Organic Chemistry, 2022, 42(3): 679-697.

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图/表 28

图1. 含叔醇结构的天然产物、药物和手性配体

Figure 1. Natural products, drugs and chiral ligands containing chiral tertiary alcohol motifs

图式1. 动力学拆分以及叔醇动力学拆分的三种策略

Scheme 1. Kinetic resolution and three strategies for kinetic resolution of tertiary alcohols

图式2. 多肽催化的叔醇酯化动力学拆分

Scheme 2. Kinetic resolution of tertiary alcohols via peptides- catalyzed esterifications

图式3. 氮杂环卡宾催化的叔醇酰化动力学拆分

Scheme 3. Kinetic resolution of tertiary alcohols via N-heterocyclic carbene-catalyzed acylation

图式4. 手性Lewis碱催化的杂环叔醇酯化动力学拆分

Scheme 4. Kinetic resolution of heterocyclic tertiary alcohols via chiral Lewis base-catalyzed esterifications

图式5. 手性Lewis碱催化的非环状叔醇酯化动力学拆分

Scheme 5. Kinetic resolution of acyclic tertiary alcohols via chiral Lewis base-catalyzed esterifications

图式6. 手性DMAP衍生物催化的杂叔醇酯化动力学拆分

Scheme 6. Kinetic resolution of heterocyclic tertiary alcohols via chiral DMAP derivative-catalyzed esterifications

图式7. 铜催化的炔丙叔醇硅-氧偶联动力学拆分

Scheme 7. Kinetic resolution of tertiary propargylic alcohols via Cu-catalyzed Si-O coupling

图式8. 手性磷酸催化的γ-羟基缩醛的缩醛交换动力学拆分

Scheme 8. Kinetic resolution of homoaldols via chiral phosphoric acid catalyzed transacetalizations

图式9. 酰亚胺二磷酸催化二醇缩醛化动力学拆分

Scheme 9. Kinetic resolution of diols via chiral confined imidodiphosphoric acid catalyzed acetalizations

图式10. 手性磷酸催化叔醇的不对称环醚化动力学拆分

Scheme 10. Kinetic resolution of tertiary alcohols via chiral phosphoric acid catalyzed cycloetherifications

图式11. 手性磷酸催化2-N-烷氧甲酰胺基取代烯丙基叔醇的分子内酯交换动力学拆分

Scheme 11. Kinetic resolution of tertiary 2-alkoxycarboxamido- substituted allylic alcohols by chiral phosphoric acid catalyzed intramolecular transesterifications

图式12. 手性磷酸催化邻酰胺取代苄叔醇的分子内脱水缩合动力学拆分

Scheme 12. Kinetic resolution of 2-amido tertiary benzyl alcohols by chiral phosphoric acid catalyzed intramolecular dehydrative condensations

图式13. 手性磷酸催化的2-N-酰胺基取代烯丙基叔醇的分子内缩合动力学拆分

Scheme 13. Kinetic resolution of 2-N-acylamido tertiary allylic alcohols by chiral phosphoric acid catalyzed intramolecular condensations

图式14. 手性磷酸催化烯丙基叔醇的环醚化动力学拆分

Scheme 14. Kinetic resolution of tertiary allylic alcohols by chiral phosphoric acid catalyzed cycloetherifications

图式15. 钯/手性降冰片烯联合催化的苄叔醇的动力学拆分

Scheme 15. Kinetic resolution of tertiary benzyl alcohols via palladium/chiral norbornene cooperative catalysis

图式16. 有机催化的1,2-二醇硅醚化动力学拆分

Scheme 16. Kinetic resolution of tertiary alcohols via organocatalyzed O-silylations of 1,2-diols

图式17. 烯丙叔醇的催化对映选择性环氧化动力学拆分

Scheme 17. Kinetic resolution of tertiary allylic alcohols through catalytic enantioselective epoxidations

图式18. 硼酸手性季铵盐催化的烷基化动力学拆分1,2-二醇

Scheme 18. Alkylative kinetic resolution of 1,2-diols via chiral ammonium borinate catalysis

图式19. 硼酸导向的手性磷酸催化对醌醇的不对称氧杂-Mi- chael加成动力学拆分

Scheme 19. Kinetic resolution of para-quinols via boronic-acid-directed chiral phosphoric acid catalyzed asymmetric oxa-Michael additions

图式20. 手性Lewis碱催化的的邻位羟基辅助叔醇酯化动力学拆分

Scheme 20. Kinetic resolution of auxiliary adjacent alcohols via chiral Lewis base-catalyzed esterifications

图式21. 手性磷酸催化不对称烯胺-亚胺异构实现叔醇动力学拆分

Scheme 21. Kinetic resolution of tertiary alcohols via chiral phosphoric acid catalyzed asymmetric enamide-imine tauto- merism

图式22. 铜催化的叠氮-炔环加成动力学拆分叔醇

Scheme 22. Kinetic resolution of tertiary alcohols via Cu(I)-catalyzed azide-alkyne cycloadditions (CuAAC)

图式23. 混合镧-锂双金属络合物催化的β-硝基叔醇的动力学拆分

Scheme 23. Kinetic resolution of β-nitro tertiary alcohols via mixed La-Li heterobimetallic complexes catalysis

图式24. 铑催化高烯丙叔醇立体选择性碳-碳键断裂动力学拆分

Scheme 24. Kinetic resolution of tertiary homoallyl alcohols via rhodium-catalyzed stereoselective carbon-carbon bond cleavage

图式25. 钯/酸催化的炔丙基叔醇的羰基化动力学拆分

Scheme 25. Kinetic resolution of tertiary propargylic alcohols through palladium/H+-cocatalyzed carboxylations

图式26. 铑催化苯甲酰胺不对称联烯基化反应实现炔丙基叔醇动力学拆分

Scheme 26. Kinetic resolution of tertiary propargylic alcohols via rhodium-catalyzed asymmetric allenylations of benzamides

图式27. 氧钒化合物和脂肪酶协同催化的叔醇动态动力学拆分

Scheme 27. Dynamic kinetic resolution of tertiary alcohol via cooperative catalysis of a lipase-catalyst & an oxovanadium catalyst

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