Abiko-Masamune羟醛缩合反应

时间:2022-05-10 08:09:37

去甲麻黄碱(或去甲伪麻黄碱)衍生物作为手性助剂的丙酸酯和醛进行不对称羟醛缩合的反应,称为Abiko-Masamune羟醛缩合反应。1997年,Abiko和Masamune首先开发了此手性助剂。此反应条件温和,非对映选择性高,广泛应用于天然产物的全合成。

此反应与Evans羟醛缩合反应类似,反应中形成了硼化烯醇酯,最后生成是 syn【3】或 anti【2】构型的产物是由二烷基(三氟甲磺酰氧基)硼烷的烷基空间位阻、手性助剂、叔胺和温度(低温更容易生成动力学产物anti构型)共同决定的。利用大位阻的二环己基(三氟甲磺酰氧基)硼烷和三乙胺通过生成E-硼烯醇酯生成anti构型的产物,而二丁基(三氟甲磺酰氧基)硼烷和DIPEA更容易生成syn构型的产物【10】。此反应的优点是可以控制条件得到anti构型的产物。乙酸酯进行此反应可能会生成双羟醛缩合产物【6】。甲氧基乙酸酯可以高选择性的制备syn构型的乙醇酸衍生物【8】。

反应机理

机理和Evans羟醛缩合类似,通过不同硼试剂的选择可以确定得到syn/anti构型。用Zimmerman-Traxler六元环过渡态模型能够较好的解释说明底物与产物立体化学关系。syn构型产物时,空间选择性和Evans羟醛缩合类似,由去甲麻黄碱的C1的构型决定最终产物构型。anti构型产物时,去甲麻黄碱C2的构型决定产物构型。

反应实例

anti Selective aldol (3). To a solution of norepinephrine ester (1R, 2S)-1 (4.80 g, 10 mmol) (R1 = Bn, R2= Mes) in CH2Cl2 (50 mL) in an oven-dried 500 mL flask under nitrogen was added via syringeTEA (3.40 mL, 24 mmol). A solution of dicyclohexylboron triflate (1.0 M in hexane, 22 mL) wasadded over 20 min at -78 ℃ and stirring was continued for 30 min. IBA 2 (R = iPr, 1.08 mL,12 mmol) was then added dropwise and the mixture was stirred at -78 ℃ for 30 min and then broughtto r.t. (1 h). After quenching with a pH 7 buffer (40 mL), MeOH (200 mL) and 30% H2O2 (20 mL)were added slowly. After stirring overnight at r.t. and usual workup and evaporation a solid wasobtained which was crystallized from hexane (150 mL) to give crude 3 (4.4 g). Removal of cyclohexanol from the mother liquor and chromatography provided an additional product (0.6 g). Crystallization from EA–hexane (1:5) afforded 4.77 g (87%) of pure anti (+)-3.syn Aldol (3).5 As above, reaction of ester (1R, 2S)-1 (R1 = Me, R2 = octahydroanthracenyl(OHA),0.4 mmol) with n-Bu2BOTf (0.8 mmol) and iPr2NEt afforded 3-syn (98%).

【J Org Chem. 2002, 67, 5250-5256】

【J. Org. Chem. 2009, 74, 19, 7220-7229】

【Tetrahedron 2010, 66, 187–196】

【Tetrahedron 2011, 67, 7485–7501】

【J. Org. Chem. 2012, 77, 1477−1488】

相关文献

1 Brown HC Tet Lett 1992 33 3421

2 Abiko A, Masamune S J Org Chem 1996 61 2590

3 Abiko A, Masamune S J Am Chem Soc 1997 119 2586

4 Abiko A, Masamune S J Am Chem Soc 2001 123 4605

5 Abiko A, Masamune S J Org Chem 2002 67 5250

6 Abiko A Org Syn 2002 79 103,116

7 Abiko A, Masamune S J Am Chem Soc 2002 124 10759

8 Andrus MB Org Lett 2002 4 3549

9 Abiko A Acc Chem Res 2004 37 387

10 Dai W-M Tetrahedron 2010 66 187

编译自:Organic Syntheses Based On Name Reactions, 3RdEd, A. Hassner, Page 1.

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