特羅斯特不對稱烯丙位烷化反應

特羅斯特不對稱烯丙位烷化反應（Trost asymmetric allylic alkylation，縮寫AAA），由巴里·特羅斯特報道。^[1]^[2]^[3]^[4]

烯丙位帶有離去基團的底物在鈀和手性配體（特羅斯特配體）作用下，與親核試劑（如醇、酚、胺、酞醯亞胺、水、烯胺^[5]）反應對映選擇性（構型翻轉）地生成相應的烯丙位取代產物。

反應底物範圍

目前已報道的烯丙基烷基化反應的底物類型包括烯丙基氯代物和溴代物、烯丙基醋酸酯和磷酸酯、烯丙基叔丁氧基碳酸酯以及烯丙基吡咯烷

反應機理

鈀(Ⅱ)與手性膦配體（如特羅斯特配體）作用，原位產生零價鈀。鈀與烯烴配位，生成η² π-烯丙-Pd⁰ π配合物。接著發生氧化加成，離去基團離去，生成η³ π-烯丙-Pd^II 物種。

然後有兩種途徑：

對於軟親核試劑，親核試劑加到烯丙位的遠端碳上，得到η² π-烯丙-Pd⁰ 絡合物，並發生解配得到最終產物
對於硬親核試劑，親核試劑則進攻金屬原子，然後再通過還原消除得到最終產物

變體

1、Helmchen 發展的以銥催化的不對稱烷化反應：^[6]^[7]^[8]

2、累積二烯底物，AAA-Wagner-Meerwein 串聯反應，完成擴環^[9]

3、聯苯和葑醇類不對稱配體^[10]

應用

1、用於加蘭他敏（galanthamine）和嗎啡的全合成^[11]

反應條件：2.5 mol% Pd₂dba₃、7.5 mol% (S,S) 特羅斯特配體、三乙胺，溶劑二氯甲烷，室溫
產物：芳醚的(−)-對映體，產率64%，ee77%

參見

化學反應列表

參考資料

^ B. M. Trost, T. J. Fullerton: New synthetic reactions. Allylic alkylation., in: J. Am. Chem. Soc. 1973, 95, 292–294.
^ B. M. Trost, T. J. Dietsch: New synthetic reactions. Asymmetric induction in allylic alkylations., in: J. Am. Chem. Soc. 1973, 95, 8200–8201.
^ B. M. Trost, P. E. Strege: Asymmetric induction in catalytic allylic alkylation., in: J. Am. Chem. Soc. 1977, 99, 1649–1651.
^ B. M. Trost, M. L. Crawley: Asymmetric Transition-Metal-Catalyzed Allylic Alkylations:Applications in Total Synthesis, in: Chem. Rev. 2003, 103, 2921–2944.
^ C-N Bond Cleavage of Allylic Amines via Hydrogen Bond Activation with Alcohol Solvents in Pd-Catalyzed Allylic Alkylation of Carbonyl Compounds Xiaohu Zhao, Delong Liu, Hui Guo, Yangang Liu, Wanbin Zhang, J. Am. Chem. Soc, 2011, 133，19354-19357 doi:10.1021/ja209373k
^ J. P. Janssen, G. Helmchen: First Enantioselective Alkylations of Monosubstituted Allylic Acetates Catalyzed by Chiral Iridium Complexes, in: Tetrahedron Lett. 1997, 109, 8025–8026.
^ B. Bartels, G. Helmchen: Ir-catalysed allylic substitution: mechanistic aspects and asymmetric synthesis with phosphorus amidites as ligands, in: Chem. Commun. 1999, 741–742.
^ G. Lipowsky, N. Miller, G. Helmchen: Regio- und enantioselektive Iridium-katalysierte allylische Alkylierung mit in situ aktivierten P,C-Chelatkomplexen, in: Angew. Chem. 2004, 116, 4695–4698.
^ Trost, B. M.; Xie, J. "Palladium-Catalyzed Asymmetric Ring Expansion of Allenylcyclobutanols: An Asymmetric Wagner-Meerwein Shift." J. Am. Chem. Soc. 2006, 128, 6044–6045. doi:10.1021/ja0602501.
^ Goldfuss, B.; Löschmann, T.; Kop-Weiershausen, T.; Neudörfl, J.; Rominger, F. "A superior P-H phosphonite: Asymmetric allylic substitutions with fenchol-based palladium catalysts." Beilstein J. Org. Chem. 2006, 2, 7–11. doi:10.1186/1860-5397-2-7.
^ Trost, B. M.; Tang, W.; Toste, F. D. "Divergent Enantioselective Synthesis of (−)-Galanthamine and (−)-Morphine." J. Am. Chem. Soc. 2005, 127, 14785–14803. doi:10.1021/ja054449+.

外部連結

Asymmetric allylic substitution: mechanism and recent advances using palladium and molybdenum Kyle D. Bodine Review

[1] B. M. Trost, T. J. Fullerton: New synthetic reactions. Allylic alkylation., in: J. Am. Chem. Soc. 1973, 95, 292–294.

[2] B. M. Trost, T. J. Dietsch: New synthetic reactions. Asymmetric induction in allylic alkylations., in: J. Am. Chem. Soc. 1973, 95, 8200–8201.

[3] B. M. Trost, P. E. Strege: Asymmetric induction in catalytic allylic alkylation., in: J. Am. Chem. Soc. 1977, 99, 1649–1651.

[4] B. M. Trost, M. L. Crawley: Asymmetric Transition-Metal-Catalyzed Allylic Alkylations:Applications in Total Synthesis, in: Chem. Rev. 2003, 103, 2921–2944.

[5] C-N Bond Cleavage of Allylic Amines via Hydrogen Bond Activation with Alcohol Solvents in Pd-Catalyzed Allylic Alkylation of Carbonyl Compounds Xiaohu Zhao, Delong Liu, Hui Guo, Yangang Liu, Wanbin Zhang, J. Am. Chem. Soc, 2011, 133，19354-19357 doi:10.1021/ja209373k

[6] J. P. Janssen, G. Helmchen: First Enantioselective Alkylations of Monosubstituted Allylic Acetates Catalyzed by Chiral Iridium Complexes, in: Tetrahedron Lett. 1997, 109, 8025–8026.

[7] B. Bartels, G. Helmchen: Ir-catalysed allylic substitution: mechanistic aspects and asymmetric synthesis with phosphorus amidites as ligands, in: Chem. Commun. 1999, 741–742.

[8] G. Lipowsky, N. Miller, G. Helmchen: Regio- und enantioselektive Iridium-katalysierte allylische Alkylierung mit in situ aktivierten P,C-Chelatkomplexen, in: Angew. Chem. 2004, 116, 4695–4698.

[9] Trost, B. M.; Xie, J. "Palladium-Catalyzed Asymmetric Ring Expansion of Allenylcyclobutanols: An Asymmetric Wagner-Meerwein Shift." J. Am. Chem. Soc. 2006, 128, 6044–6045. doi:10.1021/ja0602501.

[10] Goldfuss, B.; Löschmann, T.; Kop-Weiershausen, T.; Neudörfl, J.; Rominger, F. "A superior P-H phosphonite: Asymmetric allylic substitutions with fenchol-based palladium catalysts." Beilstein J. Org. Chem. 2006, 2, 7–11. doi:10.1186/1860-5397-2-7.

[11] Trost, B. M.; Tang, W.; Toste, F. D. "Divergent Enantioselective Synthesis of (−)-Galanthamine and (−)-Morphine." J. Am. Chem. Soc. 2005, 127, 14785–14803. doi:10.1021/ja054449+.

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