Non-Directed Allylic C-H Acetoxylation in the Presence of Lewis Basic Heterocycles.
Non-Directed Allylic C-H Acetoxylation in the Presence of Lewis Basic Heterocycles.
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DOI：
10.1039/c3sc53414f
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发表时间：
2014-06-01
期刊：
影响因子：
8.4
通讯作者：
Patterson AW
中科院分区：
文献类型：
--
作者：
Malik HA;Taylor BL;Kerrigan JR;Grob JE;Houk KN;Du Bois J;Hamann LG;Patterson AW
我们概述了一种策略，使非定向Pd（II）催化的C-H官能化的存在下，刘易斯基本杂环。在两个钯催化的C-H乙酰氧基化反应的高通量筛选中，发现添加各种含氮杂环会导致低的产物转化率。选择含吡啶的测试底物作为假设引起催化剂停滞的杂环支架的代表。我们并行地追求两种方法，其允许在该代表性系统中的产物转化：发现刘易斯酸对于刘易斯碱性位点是有效的原位阻断基团，并且示出了预形成的吡啶N-氧化物能够实现高收率的烯丙基C-H乙酰氧基化。用密度泛函理论（M06）计算所选杂环与Pd（OAc）2的结合亲和力，提供了计算的杂环-Pd（OAc）2结合亲和力与产物的实验转化率的逆相关性。此外，1H NMR结合研究为理论计算提供了实验支持。
We outline a strategy to enable non-directed Pd(II)-catalyzed C–H functionalization in the presence of Lewis basic heterocycles. In a high-throughput screen of two Pd-catalyzed C–H acetoxylation reactions, addition of a variety of N-containing heterocycles is found to cause low product conversion. A pyridine-containing test substrate is selected as representative of heterocyclic scaffolds that are hypothesized to cause catalyst arrest. We pursue two approaches in parallel that allow product conversion in this representative system: Lewis acids are found to be effective in situ blocking groups for the Lewis basic site, and a pre-formed pyridine N-oxide is shown to enable high yield of allylic C–H acetoxylation. Computational studies with density functional theory (M06) of binding affinities of selected heterocycles to Pd(OAc)2 provide an inverse correlation of the computed heterocycle–Pd(OAc)2 binding affinities with the experimental conversions to products. Additionally, 1H NMR binding studies provide experimental support for theoretical calculations.