An efficient method for the selective iridium-catalyzed monoalkylation of (hetero)aromatic amines with primary alcohols
An efficient method for the selective iridium-catalyzed monoalkylation of (hetero)aromatic amines with primary alcohols
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DOI：
10.1002/adsc.200700596
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发表时间：
2008-03-01
影响因子：
5.4
通讯作者：
Kempe, Rhett
中科院分区：
文献类型：
--
作者：
Blank, Benoit;Madalska, Martyna;Kempe, Rhett
描述了一种高效的多克规模合成各种P，N配体的方案。该合成在两步反应中实现。首先，胺被去质子化，随后加入氯膦以产生相应的P，N配体。胺的去质子化通常用n-BuLi在低温下实现，但为了制备具有2，2 '-二吡啶基氨基骨架的配体和具有高空间需求的膦，KH必须与110 ℃的反应温度结合用于盐复分解步骤。将两当量的所选P，N配体与一当量的铱络合物[IrCl（cod）]（2）（cod= 1，5-环辛烯）反应，以定量产率得到P，N配体配位的铱络合物。X-射线单晶结构分析这些配合物之一，揭示了一个单体的五配位结构在固态。铱配合物被用来形成催化剂，用于芳香胺与醇的N-烷基化。通过对8种不同的磷、氮配体、9种不同的溶剂和14种不同的碱的研究，对催化体系进行了优化。系统变化的基板碱和胺醇的比例以及催化剂负载导致优化的催化反应条件。通过合成20种不同的胺，其中12种可以以高于90%的分离产率获得所开发的催化方案的底物范围。建立了一种新的高效催化剂体系，用于芳香伯胺和杂芳香伯胺与芳香伯醇、杂芳香伯醇和脂肪伯醇的选择性单烷基化反应。反应在相当适度的催化剂负载下进行。
An efficient multi-gram scale synthesis protocol of a variety of P,N ligands is described. The synthesis is achieved in a two-step reaction. First, the amine is deprotonated and subsequently the chlorophosphine is added to yield the corresponding P,N ligand. Deprotonation of the amine is normally achieved with n-BuLi at low temperature, but for the preparation of ligands with a 2,2'-dipyridylamino backbone and phosphines with a high steric demand KH has to be employed in combination with reaction temperatures of 110 degrees C for the salt metathesis step. The reaction of two equivalents of a selected P,N ligand with one equivalent of the iridium complex [IrCl(cod)](2) (cod=1,5-cyclooctadiene) affords P,N ligand-coordinated iridium complexes in quantitative yield. X-Ray single crystal structure analysis of one of these complexes reveals a monomeric five-coordinated structure in the solid state. The iridium complexes were used to form catalysts for the N-alkylation of aromatic amines with alcohols. The catalyst system was optimized by studying 8 different P,N ligands, 9 different solvents and 14 different bases. Systematic variation of the substrate to base and the amine to alcohol ratios as well as the catalyst loading led to optimized catalytic reaction conditions. The substrate scope of the developed catalytic protocol was shown by synthesizing 20 different amines of which 12 could be obtained in isolated yields higher than 90%. A new efficient catalyst system for the selective monoalkylation of primary aromatic and heteroaromatic amines with primary aromatic, heteroaromatic as well as aliphatic alcohols has been established. The reaction proceeds with rather moderate catalyst loadings.