手性伯胺催化逆-Claisen反应的对映选择性控制
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- 英文论文题名：The Enantio-Control in Chiral Primary Amine Catalyzed Retro-Claisen Reaction
- 论文作者：张龙 ; 朱云博 ; 罗三中
- 英文论文作者：Long Zhang ; Yunbo Zhu ; Sanzhong Luo ; CAS Key Laboratory of Molecular Recognition and Function
- 年：2016
- 作者机构：中国科学院化学研究所分子识别与功能实验室;
- 论文关键词：仿生催化 ; 逆-Claisen反应 ; 不对称质子化 ; 不对称烷基化 ; 理论计算
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第四十五分会：物理有机
- 语种：中文
- 分类号：O621.251
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第四十五分会 ; 物理有机
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：316k
- 原文格式：D
- 会议级别：全国
摘要
逆-Claisen反应过程广泛存在于人体新陈代谢、生物降解及生物催化过程中,并已成为有机合成中常用的碳碳键切断策略。~1然而该过程的手性控制极具挑战性,至今仍未见文献报导。最近,我们报道了首例仿生有机小分子催化的不对称逆-Claisen反应。~2机理研究表明该反应经由烯胺催化历程进行。。计算研究表明该反应历程中的烯胺形成、烷基化、碳碳键断裂以及质子化过程均具有极高的立体选择性,但反应中存在亚胺中间体(iminium int1)水解生成消旋产物的竞争过程。研究发现二元酸可有效降低不对称质子化过程的能垒,从而可抑制亚胺中间体水解过程。
Retro-Claisen reaction is a useful tool in C-C bond cleavage of β-carbonyl compounds. However, the asymmetric version of this process has not been described to date. Recently, we have developed an enantio-controlled RetroClaissen reaction with the aid of chiral primary amine catalysis. Detailed computational studies have been proformed and it was found that all of the main steps, including the enamine formation, the alkylation of ketones, the C-C bond cleavage as well as the enamine protonation, were highly stereoselective process. A competing racemic product formation pathway was also found, which was initiated with the hydrolysis of imine moiety in the stable ketal intermediate 1. When dicarboxylic acids were used as additive, this racemic process could be dramatically inhibited, thus facilitating high stereoinduction.
Retro-Claisen reaction is a useful tool in C-C bond cleavage of β-carbonyl compounds. However, the asymmetric version of this process has not been described to date. Recently, we have developed an enantio-controlled RetroClaissen reaction with the aid of chiral primary amine catalysis. Detailed computational studies have been proformed and it was found that all of the main steps, including the enamine formation, the alkylation of ketones, the C-C bond cleavage as well as the enamine protonation, were highly stereoselective process. A competing racemic product formation pathway was also found, which was initiated with the hydrolysis of imine moiety in the stable ketal intermediate 1. When dicarboxylic acids were used as additive, this racemic process could be dramatically inhibited, thus facilitating high stereoinduction.
引文
[1](a)Siirola,E.;Frank,A.;Grogan,G.;Kroutil,W.Adv.Synth.Catal.2013,355:1677.(b)Grogan,G.Biochem.J.2005,388:721.
[2]Zhu,Y.;Zhang,L.;Luo,S.J.Am.Chem.Soc.2016,138:3978.
[2]Zhu,Y.;Zhang,L.;Luo,S.J.Am.Chem.Soc.2016,138:3978.