本文選題：N-O雙咔啉伯酰胺 + 不對(duì)稱(chēng)硅氫化反應(yīng)��； 參考：《河北大學(xué)》2017年碩士論文

【摘要】：手性胺是一類(lèi)非常重要的藥物合成中間體,已知的多種藥物都是手性胺或其衍生物類(lèi),并且越來(lái)越多的手性胺分子是非外消旋的,因此通過(guò)不對(duì)稱(chēng)合成手性胺成為人們研究的熱點(diǎn)。本論文主要設(shè)計(jì)合成了伯酰胺結(jié)構(gòu)的軸手性雙咔啉N-O化物和軸手性磷配體雙咔啉氮氧化物這兩類(lèi)催化劑,并探究了這兩類(lèi)催化劑對(duì)酮亞胺的不對(duì)稱(chēng)硅氫化反應(yīng)中的催化作用。首先以L-色氨酸為原料通過(guò)酯化、Pictet-Spengler反應(yīng)、脫氫、水解、甲基化、�；�、N-氧化反應(yīng)合成了5個(gè)新的伯酰胺結(jié)構(gòu)的軸手性雙咔啉N-O催化劑,N~2,N~2'-二氧-9,9'-二甲基-3,3'-二-β-咔啉酰胺,并考察了其在不對(duì)稱(chēng)催化酮亞胺的還原反應(yīng)中的催化效果。結(jié)果表明,反應(yīng)能夠在0℃的溫和條件下,24 h內(nèi)反應(yīng)完成,催化劑的催化轉(zhuǎn)化率達(dá)到了80%~98%,立體選擇性(%ee)最高達(dá)到了68%。通過(guò)分析催化劑的結(jié)構(gòu)可以發(fā)現(xiàn),C-3,C-3′位為環(huán)酰胺時(shí)具有較好的立體選擇性,而C-3,C-3′位為鏈狀酰胺時(shí)催化效果一般。通過(guò)對(duì)底物結(jié)構(gòu)與催化效果的分析表明:催化劑對(duì)含有供電子取代基的酮亞胺催化效果優(yōu)于吸電子取代基的酮亞胺。其中用量為5 mol%的環(huán)己基胺縮合的氮氧化物在催化對(duì)甲氧基取代的酮亞胺催化轉(zhuǎn)化率達(dá)到了98%,%ee值達(dá)到68%。鑒于磷配體類(lèi)催化劑在不對(duì)稱(chēng)催化反應(yīng)中的優(yōu)良性質(zhì),我們又設(shè)計(jì)并合成了以雙咔啉醇為骨架的新型磷配體雙咔啉氮氧催化劑,并考察了其在醛的不對(duì)稱(chēng)烯丙基化、酮亞胺的不對(duì)稱(chēng)硅氫化、不對(duì)稱(chēng)MBH反應(yīng)的催化效果。但是經(jīng)過(guò)對(duì)磷配體雙咔啉氮氧催化劑在不同的反應(yīng)條件下進(jìn)行了篩選后,均未發(fā)現(xiàn)催化轉(zhuǎn)化活性。綜上,本研究合成了一系列伯酰胺結(jié)構(gòu)的軸手性雙咔啉氮氧化和磷配體雙咔啉氮氧化催化劑,并用于不對(duì)稱(chēng)催化酮亞胺的還原反應(yīng),其中催化劑16b的催化活性較好,轉(zhuǎn)化率達(dá)到了98%,%ee達(dá)到了68%。成功擴(kuò)大了酮亞胺還原的催化劑范圍。
[Abstract]:Chiral amines are very important intermediates for drug synthesis. Many known drugs are chiral amines or their derivatives, and more and more chiral amine molecules are non-racemic. Therefore, asymmetric synthesis of chiral amines has become a hot topic. In this paper, the chiral dicarboline N-O catalysts with primary amide structure and dicarboline nitrogen oxides with chiral phosphorus ligand were synthesized, and the catalytic effects of these two catalysts on the asymmetric hydrosilylation of keto-imine were investigated. Firstly, five new chiral dicarboline N-O catalysts with primary amide structure were synthesized from L-tryptophan by the esterification of Pictet-Spengler, dehydrogenation, hydrolysis, methylation, acylation and N-oxidation. Its catalytic effect in asymmetric reduction of keto-imine was also investigated. The results showed that the reaction could be completed in 24 h at 0 鈩，

本文編號(hào)：1836367