Isothiourea-Catalyzed Enantioselective Addition of 4-Nitrophenyl Esters to Iminium Ions
Isothiourea-Catalyzed Enantioselective Addition of 4-Nitrophenyl Esters to Iminium Ions
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DOI：
10.1021/acscatal.7b02697
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发表时间：
2018-02-01
期刊：
影响因子：
12.9
通讯作者：
Smith, Andrew D.
中科院分区：
文献类型：
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作者：
Arokianathar, Jude N.;Frost, Aileen B.;Smith, Andrew D.
异硫脲催化4-硝基苯酯与四氢异喹啉衍生的亚胺离子的对映选择性加成。4-硝基苯酚盐，由4-硝基苯基酯对异噻唑烷的初始N-酰化原位产生，用于促进该反应过程中的催化剂周转。优化结果表明，4-硝基苯酯给出了最好的反应性，在这个协议的范围内的替代芳基酯，所观察到的对映选择性显着依赖于性质的亚胺counterparts。最高的产率和对映体选择性使用溴化亚胺离子获得通过使用BrCCl 3和Ru（bpy）（3）Cl-2（0.5摩尔%）和市售的四咪唑（5摩尔%）作为刘易斯碱催化剂的光氧化还原催化原位产生。开发了该方法的范围和限制，得到所需的β-氨基酰胺产物，产率高达96%，非对映异构体比率（dr）为79：21，er（主要（2 R，1 ′ S））为99.5：0.5。
Isothioureas catalyze the enantioselective addition of 4-nitrophenyl esters to tetrahydroisoquinoline-derived iminium ions. 4-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the 4-nitrophenyl ester, is used to facilitate catalyst turnover in this reaction process. Optimization showed that 4-nitrophenyl esters give the best reactivity in this protocol over a range of alternative aryl esters, with the observed enantioselectivity markedly dependent on the nature of the iminium counterion. Highest yields and enantioselectivity were obtained using iminium bromide ions generated in situ via photoredox catalysis using BrCCl3 and Ru(bpy)(3)Cl-2 (0.5 mol %) and commercially available tetramisole (5 mol %) as the Lewis base catalyst. The scope and limitations of this procedure was developed, giving the desired beta-amino amide products in up to 96% yield, 79:21 diastereomeric ratio (dr), and er(major(2R,1'S)) 99.5:0.5.