手性α-芳基酮的催化合成研究进展

doi:10.6023/cjoc202408031

摘要/Abstract

手性α-芳基酮是一类重要的分子骨架, 广泛存在于高价值目标分子中, 同时也是高效合成其它核心骨架的前体. 因此, 催化合成手性α-芳基酮一直是有机化学领域的研究热点之一, 受到了有机化学家们的广泛关注. 在过去的几十年里, 手性α-芳基酮的合成取得了重大进展. 综述了近20年来通过不对称偶联反应实现手性α-芳基酮催化不对称合成领域的研究进展. 此外, 还展望了该领域的未来发展方向.

关键词: α-芳基酮, 不对称催化, 偶联反应, 过渡金属催化, 有机催化

Enantioenriched α-arylated ketones are ubiquitous subunits in valuable target molecules and serve as versatile synthetic precursors for other functional groups. Thus, the development of catalytic syenthesis of asymmetric α-arylated ketones remains one of the research topics in organic chemistry and has attracted great attention from synthetic chemists. Over the past decades, great efforts have been devoted to the synthesis of enantioenriched α-arylated ketones. The recent progress of catalytic foramtion of enantioenriched α-arylated ketones is reviewed. Moreover, the future directions and efforts for further development of divese enabling catalytic means to directly and effectively obtain enantioenriched α-arylated ketones are discussed.

Key words: α-arylated ketone, asymmetric catalysis, cross-coupling reaction, transition-metal-catalysis, organocatalysis

引用此文

杜一鸣, 贾均松, 李玉龙, 舒伟. 手性α-芳基酮的催化合成研究进展[J]. 有机化学, 2025, 45(6): 1838-1870.

Yiming Du, Junsong Jia, Yulong Li, Wei Shu. Recent Progress on Catalytic Synthesis of Enantioenriched α-Arylated Ketones[J]. Chinese Journal of Organic Chemistry, 2025, 45(6): 1838-1870.

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图/表 57

图1. 含有手性α-芳基酮片段的代表性分子

Figure 1. Representative molecules containing enantioenriched α-arylated ketones

图式1. 手性α-芳基酮的催化合成方法

Scheme 1. Catalytic methods to construct chiral α-arylated ketones

图式2. 钯催化环状酮与芳基溴的不对称α-芳基化反应

Scheme 2. Pd-catalyzed asymmetric α-arylation of cyclic ketones with aryl bromides

图式3. 钯催化α-烯基环状酮的不对称α-芳基化反应

Scheme 3. Pd-catalyzed asymmetric α-arylation of ketone enolates

图式4. 铜催化N-酰基邻碘苯胺与β-酮酯的不对称偶联反应

Scheme 4. Cu-catalyzed asymmetric coupling of N-acyl o-iodoanilines with β-ketone esters

图式5. 钯或镍催化环状酮与芳基三氟甲磺酸酯的不对称α-芳基化反应

Scheme 5. Pd or Ni-catalyzed asymmetric α-arylation of cyclic ketones with aryl triflates

图式6. 镍催化环状酮与芳基氯代物的不对称α-芳基化反应

Scheme 6. Ni-catalyzed asymmetric α-arylation of cyclic ketones with aryl chlorides

图式7. 钯催化α-氟代环状酮的不对称α-芳基化反应

Scheme 7. Pd-catalyzed asymmetric α-arylation of cyclic α-fluoroketones

图式8. 烯烃氢酰基化和镍催化不对称α-芳基化串联反应

Scheme 8. Hydroacylation of alkenes and Ni-catalyzed asymmetric α-arylation cascade

图式9. 电化学条件下钴和胺协同催化1,3-二羰基化合物的不对称α-芳基化反应

Scheme 9. Electrochemical cobalt-and amine-cocatalyzed asymmetric α-arylation reaction of 1,3-dicarbonyl compounds

图式10. 手性伯胺催化β-二酮的不对称α-芳基化反应

Scheme 10. Chiral primary amine-catalyzed α-arylation of β-diketones

图式11. 手性氮杂双噁唑啉-锌催化的不对称逆克莱森反应

Scheme 11. Chiral aza-bisoxazoline-zinc catalyzed retro-Claisen reaction

图式12. 手性相转移催化剂催化β-酮酰胺与苯炔的不对称α-芳基化反应

Scheme 12. Chiral phase-transfer-catalyst catalyzed asymmetric α-arylation of β-ketoamides with arynes

图式13. 钯/L-脯氨酸催化环己酮分子内不对称α-芳基化反应

Scheme 13. Pd/L-proline catalyzed intramolecular asymmetric α-arylation of cyclohexanones

图式14. 钯催化1,3-二酮去对称化不对称芳基化反应

Scheme 14. Pd-catalyzed asymmetric α-arylative desymmetrization of 1,3-diketones

图式15. 钯/胺协同催化环丁酮去对称化不对称α-芳基化反应

Scheme 15. Pd/amine co-catalyzed asymmetric α-arylative desymmetrization of cyclobutanones

图式16. 钯催化环状酮的不对称α-芳基化反应

Scheme 16. Pd-catalyzed asymmetric α-arylation of cyclic ketones

图式17. 钯催化环状酮分子内不对称α-芳基化构建螺环季碳手性中心

Scheme 17. Pd-catalyzed intramolecular asymmetric α-arylation of cyclic ketones to construct spirocycles with quaternary carbon stereocenters

图式18. 手性磷酸催化α-芳基环状酮与N-酰基联烯胺的不对称加成反应

Scheme 18. Chiral phosphoric acid catalyzed asymmetric addition of α-arylated cyclic ketones to allenamides

图式19. 手性磷酸/钯协同催化α-芳基环状酮不对称α-烯丙基化反应

Scheme 19. Chiral phosphoric acid/Pd-catalyzed asymmetric α-allylation of α-aryl cyclic ketones

图式20. 手性磷酸催化外消旋α-炔基α-芳基酮与N-酰基联烯胺的不对称加成反应

Scheme 20. Chiral phosphoric acid-catalyzed asymmetric additions of α-alkynyl-α-aryl ketones to allenamides

图式21. 铁催化2-酰基咪唑与烷烃的不对称自由基交叉偶联反应

Scheme 21. Fe-catalyzed asymmetric α-alkylation of 2-acylimidazoles via dehydrogenative radical cross-coupling with akanes

图式22. 手性磷酸催化α-芳基环状酮的不对称胺化反应

Scheme 22. Chiral phosphoric acid catalyzed asymmetric amination of α-arylated cyclic ketones

图式23. 手性磷酸催化外消旋α-炔基α-芳基酮的不对称胺化反应

Scheme 23. Chiral phosphate-catalyzed enantioselective amination of α-alkynyl α-aryl ketones

图式24. 手性磷酸催化外消旋α-芳基炔酮不对称胺化动力学拆分

Scheme 24. Chiral phosphate-catalyzed kinetic resolution of racemic α-aryl alkynones for asymmetric aminations

图式25. 手性磷酸催化α-芳基酮与1,4-苯醌的不对称α-芳氧基化反应

Scheme 25. Chiral phosphoric acid-catalyzed asymmetric α-aryloxylation of α-aryl ketones with 1,4-benzoquinone

图式26. 钯催化烯醇的不对称芳基化反应

Scheme 26. Pd-catalyzed enantioselective arylation of ketones

图式27. 通过新型Cu(I)-双(膦)氧化物催化体系实现对映选择性酮的α-芳基化反应

Scheme 27. Enantioselective α-arylation of ketones via a novel Cu(I)-bis(phosphine) dioxide catalytic system

图式28. 镍催化α-溴代酮与芳基锌试剂的不对称交叉偶联反应

Scheme 28. Ni-catalyzed asymmetric cross-coupling of α-bromoketones with aryl zinc reagents

图式29. 镍催化α-溴代酮与芳基格氏试剂的不对称交叉偶联反应

Scheme 29. Ni-catalyzed asymmetric cross-coupling of α-bromoketones with aryl Grignard reagents

图式30. 镍催化α-溴代α-氟酮与芳基锌试剂不对称交叉偶联反应

Scheme 30. Ni-catalyzed asymmetric cross-coupling of α-bromo-α-fluoroketones with aryl zinc reagents

图式31. 钴催化α-溴代酮与芳基锌试剂的不对称交叉偶联反应

Scheme 31. Co-catalyzed asymmetric cross-coupling of α-bromo ketones with aryl zinc reagents

图式32. 镍催化苄氯与酰氯的不对称交叉偶联反应

Scheme 32. Nickel-catalyzed asymmetric cross-coupling reactions of benzyl chlorides with acyl chlorides

图式33. 手性噁唑硼鎓离子催化芳基重氮烷烃的不对称形式插入醛的C—H键反应

Scheme 33. Chiral oxazaborolidinium ion catalytic asymmetric formal in-sertion of aryldiazoalkanes into the C—H bond of aldehydes

图式34. 钯催化外消旋苄基锌试剂与硫酯的立体汇聚式交叉偶联反应

Scheme 34. Pd-catalyzed stereoconvergent cross-coupling of racemic benzylic zinc reagents with thioesters

图式35. 可见光介导镍催化苄基不对称酰基化

Scheme 35. Visible-light mediated Ni-catalyzed benzylic asy-mmetric acylation

图式36. 可见光和镍催化苄位C—H不对称酰基化反应

Scheme 36. Visible-light and Ni-catalyzed asymmetric acylation of benzylic C—H bond

图式37. 镍催化的多组分偶联: 烯烃还原氢羰基化反应

Scheme 37. Ni-catalyzed multicomponent coupling: reductive hydrocarbonylation of alkenes

图式38. 钯催化酰氯与苄基三氟硼酸盐的立体专一交叉偶联反应

Scheme 38. Pd-catalyzed stereospecific cross-coupling of acyl chlorides with benzyl trifluoroborates

图式39. 光氧化还原/镍催化酸酐与仲烷基三氟硼酸盐的立体汇聚式偶联反应

Scheme 39. Photoredox/Nickel-catalyzed enantioconvergent acylation of secondary alkyltrifuoroborate with anhydrides

图式40. NHC催化的α-取代苯乙烯类化合物分子内不对称氢酰化反应

Scheme 40. NHC-catalyzed asymmetric intramolecular hydroacylation of α-substituted styrene

图式41. 氮杂环卡宾催化的α-取代苯乙烯类化合物分子内不对称氢酰化反应

Scheme 41. NHC-catalyzed enantioselective intramolecular hydroacylation of α-substituted styrenes

图式42. 铜氢催化芳基烯烃和芳基羧酸酐的不对称还原偶联反应

Scheme 42. CuH-catalyzed enantioselective reductive coupling of aryl alkenes and aryl carboxylic anhydrides

图式43. 铜氢催化α,β-不饱和羧酸与芳基烯烃不对称氢酰基化反应

Scheme 43. CuH-catalyzed asymmetric hydroacylation of α,β-unsaturated carboxylic acids with aryl olefins

图式44. 钴催化三取代烯烃对映和非对映选择性分子内氢酰化反应

Scheme 44. Co-catalyzed enantio-and diastereoselective intramolecular hydroacylation of trisubstituted alkenes

图式45. 钯催化烯烃的不对称酰基氨基甲酰化反应

Scheme 45. Pd-catalyzed asymmetric acyl-carbamoylation of alkenes

图式46. 配体接力催化烯烃的不对称迁移还原酰基化反应

Scheme 46. Ligand relay catalysis enabled asymmetric migratory reductive acylation of alkenes

图式47. 手性N,N'-双氧-Sc(OTf)3配合物催化芳基酮与α-重氮酯的分子内不对称同系化反应

Scheme 47. Chiral N,N'-dioxide-Sc(OTf)3 complex catalyzed intramolecular asymmetric homologation of aryl ketones with α-diazo esters

图式48. 铑催化不对称卡宾插入B—H键反应

Scheme 48. Rh-catalyzed asymmetric carbene insertion into B—H bonds

图式49. 无碱条件下铑催化环戊-4-烯-1,3-二酮的不对称氢芳基化反应

Scheme 49. Rh-catalyzed asymmetric hydroarylation of cylopent-4-ene-1,3-diones under base-free conditions

图式50. 可见光介导下手性磷酸催化α-支链乙烯基酮与乙烯基吡啶的还原交叉不对称质子化反应

Scheme 50. Visible-light mediated, chiral phosphoric acid-catalyzed reductive cross coupling and enantioselective protonation of α-branched vinyl ketone with vinyl pyridine

图式51. 可见光和叔胺催化α-芳基吡啶酮去外消旋化反应

Scheme 51. Visible-light and tertiary amine-catalyzed deracemization of α-arylpyridones

图式52. 可见光和叔胺催化α-芳基吡啶酮去外消旋化反应机理

Scheme 52. Possible mechanism of visible-light and tertiary amine-catalyzed deracemization of α-arylpyridones

图式53. 光诱导手性磷酸催化对映选择性合成N-芳基吡咯

Scheme 53. Visible-light-induced, phosphoric acid catalyzed atroposelective synthesis of N-arylpyrroles

图式54. 可见光和手性磷酸催化对映选择性合成α,α-二芳基酮

Scheme 54. Visible-light and phosphoric acid catalyzed enantioselective synthesis of α,α-diarylketones

图式55. 手性磷酸催化对映选择性合成α,α-二芳基酮

Scheme 55. Chiral phosphoric acid catalyzed enantioselective synthesis of α,α-diaryl ketones

图式56. 可见光介导下手性磷酸催化的自由基交叉偶合和对映选择性质子化反应

Scheme 56. Visible-light mediated, chiral phosphoric acid catalyzed radical-radical coupling and enantioselective protonation reaction

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