靛红衍生的硝酮与酮亚胺的不对称直接氮杂插烯Mannich反应

发布时间：2018-04-16 02:13

本文选题：不对称催化 + 有机催化　；参考：《化学学报》2017年10期

【摘要】：不对称直接插烯Mannich反应是一类高效构建手性δ-氨基-α,β-不饱和羰基化合物的方法,但这类反应主要局限于以γ-丁烯酸内酯及类似物和α,α-二氰基烯烃等作为亲核试剂前体,因此发展新的插烯亲核试剂尤为重要.本工作报道了一类从靛红衍生且含N-CH结构的硝酮化合物,由于氧化吲哚骨架的强吸电子效应能在温和碱性条件下生成氮杂二烯醇中间体,高效与靛红衍生的亚胺发生直接氮杂插烯Mannich反应.采用金鸡纳碱衍生的手性双功能叔胺硫脲催化剂,以高收率(70%~97%)、高立体选择性(83%~99%ee,19∶1 dr)合成富官能团化并含相邻季碳-叔碳手性中心的硝酮化合物,且可进一步与缺电烯烃发生[3+2]偶极环加成反应构建含有氢化异VA唑环的吲哚螺环复杂骨架.这类靛红衍生的硝酮作为氮杂插烯亲核试剂可能在不对称合成中具有更为广阔的应用.
[Abstract]:Asymmetric direct intercalation (Mannich) reaction is a highly efficient method for the synthesis of chiral 未 -amino-伪, 尾 -unsaturated carbonyl compounds, but these reactions are mainly confined to 纬 -butenolactone and its analogues and 伪, 伪 -dicyanofenes as precursors of nucleophilic reagents.So it is very important to develop new nucleophilic reagent.In this paper, we report a class of nitroketones derived from indirubin and containing N-CH structure. Because of the strong electron absorption effect of the indole-oxide skeleton, the intermediate of azadienol can be formed under mild alkaline conditions.Direct Mannich reaction of azarene with imines derived from indirubin is highly effective.In this paper, chiral difunctional tertiary amine thiourea catalyst derived from cinchona base was used to synthesize nitroketones with rich functional groups and adjacent quaternary carbon-tertiary carbon chiral centers with high yield of 70% and 97% and high stereoselectivity of 839% ~ 19: 1 dr.Furthermore, the [32] dipolar cycloaddition reaction with electrically deficient olefin can be used to construct the complex framework of indole snail ring containing isovalazole ring.As a nucleophilic reagent of nitrogen hetero-alkene, this kind of indigo derivative nitrone may have a wider application in asymmetric synthesis.
【作者单位】：四川大学华西药学院;
【基金】：国家自然科学基金(No.21602143)资助~~
【分类号】：O621.25

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