Versatile and Enantioselective Preparation of Planar-Chiral Metallocene-Fused 4-Dialkylaminopyridines and Their Application in Asymmetric Organocatalysis
Versatile and Enantioselective Preparation of Planar-Chiral Metallocene-Fused 4-Dialkylaminopyridines and Their Application in Asymmetric Organocatalysis
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DOI：
10.1021/acscatal.9b04438
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发表时间：
2020-01
期刊：
影响因子：
12.9
通讯作者：
Kazuhiro Yoshida;Qiang-Ren Liu;Risa Yasue;Shiro Wada;Ryosuke Kimura;Takuma Konishi;M. Ogasawara
中科院分区：
文献类型：
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作者：
Kazuhiro Yoshida;Qiang-Ren Liu;Risa Yasue;Shiro Wada;Ryosuke Kimura;Takuma Konishi;M. Ogasawara
合成了一系列二茂铁稠合的平面手性N-对甲苯磺酰基-4-吡啶酮（S）-2b-d。以手性二茂铁基缩醛为原料，合成了1-[（2S，4S）-4-甲氧基甲基-1，3-二氧杂环己烷-2-基]-1 ′，2 ′，3 ′，4 ′，5 ′-R5-二茂铁（（-）-3b，R = Me;（-）-3c，R = Ph;（-）-3d，R = Bn），N-甲苯磺酰胺基和甲酰基分别引入到（S）-11b-d的二茂铁核的1-和2-位上，控制了平面手性。炔丙醇衍生物（S）-17与溴化乙炔镁反应后，经MnO 2和四丁基溴化铵催化，碘催化环化反应，得到平面手性吡啶酮。该方法具有较高的实用性，无需使用贵金属催化剂，反应时间短，产率高。以平面手性铁-吡啶酮（S）-2b-d为原料，通过去甲苯磺酰化胺化反应，合成了一系列二茂铁稠合的4-二烷基氨基吡啶（（S）-1，DAAP）化合物。还以相同的方式制备了氰甾烯融合的DAAP。在这两个不对称反应中考察了手性DAAP库作为有机催化剂的催化性能，发现一些新制备的Fc-DAAP表现出了比已知种类更好的对映选择性。
A series of ferrocene-fused planar-chiral N-tosyl-4-pyridones (S)-2b-d were prepared in enantiomerically pure forms. Starting with the chiral ferrocenyl acetals, 1-[(2S,4S)-4-methoxymethyl-1,3-dioxan-2-yl]-1',2',3',4',5'-R5-ferrocenes ((–)-3b, R = Me; (–)-3c, R = Ph; (–)-3d, R = Bn), N-tosylamino and formyl groups were introduced at the 1- and 2-positions of the ferrocene cores in (S)-11b-d with control of the planar chirality. After the reaction with ethynylmagnesium bromide, generated propargyl alcohol derivatives (S)-17 were treated with MnO2 and catalytic TBAI to give the planar-chiral pyridones by the iodide-catalyzed cyclization. This method is highly practical with a shorter and higher-yield sequence without using noble metal catalysts. Planar-chiral ferroco-pyridones (S)-2b-d were reacted with various Me3Si-NR'2 to give a library of ferrocene-fused 4-dialkylaminopyridines ((S)-1, DAAPs) in high yields as single-enantiomers by the detosylative amination. The cymantrene-fused DAAPs were also prepared in the same way. The library of the chiral DAAPs were examined in the two asymmetric reactions as organocatalysts, and some newly prepared Fc-DAAPs showed better enantioselectivity than the known species.