【作者】 陈慧；

【导师】 黄焰根；

【作者基本信息】 东华大学 ， 有机化学， 2012， 硕士

【摘要】 近年来,在不对称合成含氟胺类化合物中,手性辅基叔丁基亚磺酰胺吸引了很多化学家的关注。将叔丁基亚磺酰胺与含氟醛酮反应生成亚胺,然后与有机金属试剂发生1,2-加成反应,可以不对称选择性地实现含氟胺类化合物的合成。第一部分：我们先以(SS)-叔丁基亚磺酰胺为原料,在路易斯酸Ti(OEt)4催化下与二氟甲基取代的酮脱水缩合制备二氟甲基取代的手性叔丁基亚磺酰酮亚胺,然后对其与炔基锂的1,2-亲核加成反应进行了深入研究,以较好的产率(51-93%)和优良的非对映选择性(85：15-93：7)合成了一系列手性的α-二氟甲基α-炔丙基亚磺酰胺衍生物,最后在HCl/1,4-dioxane体系中脱掉叔丁基亚磺酰基,高产率地(90-95%)得到相对应的光学纯的α-二氟甲基α-炔丙胺5。在此加成反应中路易斯酸Ti(OiPr)4对产率的提高起到了关键的作用,而且,相对于非氟底物而言,二氟甲基基团增强了亚胺的反应活性和提高了反应的非对映选择性。第二部分：利用前一章建立起来的方法体系对α-单氟甲基α-炔丙胺的合成进行了尝试,使用直接氟化试剂Selectfluor与芳基(烃基)乙酮在微波条件下进行直接氟化反应得到单氟代芳基(烃基)乙酮,再将该原料与叔丁基亚磺酰胺反应制备单氟甲基取代的酮亚胺,由于亚胺水解稳定性较低,在纯化后直接进行下一步与炔基锂的加成反应。虽然尝试了不同的溶剂和路易斯酸体系(Ti(OEt)4/THF, BF3·Et2O/THF和Ti(OEt)4/n-Hexane),但最终并没有得到目标产物α-单氟甲基α-炔丙胺衍生物。更多还原

【Abstract】 In recent years, N-tert-butanesulfinamide as a chiral auxiliary has attracted much attention in the asymmetric synthesis of fluorine-containing amines. The 1,2-addition of organolithium reagents to N-tert-butanesulfinyl ketimines or aldimines which synthesized from N-tert-butanesulfinamide and ketones or aldehydes can achieve the asymmetric synthesis of fluorine-containing amines.Part I:Stereoselective approach for preparation of a-difluoromethylated a-propargylamines has been developed. Firstly, (S)-N-tert-butanesulfinamide was used as the starting material and reacted with difluoroacetyl derivatives 1. The condensation reaction underwent smoothly when using THF as solvent and Ti(OEt)4 as Lewis acid.1,2-Addition of Lithium acetylides to diverse chiral difluoromethylated (S)-N-tert-butanesulfinyl ketimines by using Ti(O’Pr)4 as catalyst and THF as solvent afforded N-tert-butanesulfinamides in good to excellent yields (51-93%) and good diastereoselectivities (dr.85:15 to 93:7). The N-tert-butanesulfinyl group can be readily cleaved under mild acidic condition (4 M HC1 in dioxane) to provide the corresponding a-difluoromethylated a-propargylamine in excellent yields (90-95%). In this addition reaction, the Lewis acid Ti(OiPr)4 has played a key role on the increase of reaction yield, meanwhile, difluoromethyl group enhanced the reactivity of imines and diastereoselectivity of the addition reaction compared to non-fluorine containing analogues.PartⅡ:According to the method established as above, asymmetric synthesis of a-monofluoromethylated a-propargylamines is attempted. Firstly, monofluorinated acetophenones 6 were prepared by direct fluorination of aryl (alkyl) acetophenone with Selectfluor under microwave condition. Then monofluoromethylated (S)-N-tert-butanesulfinyl ketimines were synthesized and isolated prior to the next nucleophilic addition with Lithium acetylides. However, the desired a-monofluoromethylated a-propargylamines have not been achieved under several reaction conditions such as using different solvents and Lewis acids (Ti(OEt)4/THF, BF3·Et2O/THF and Ti(OEt)4/n-Hexane).更多还原