去甲麻黄碱（或去甲肾上腺素）作为手性助剂的丙酸酯和醛进行不对称羟醛缩合的反应。反应中形成了硼烯醇酯，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】。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】

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.