Rational and Predictable Chemoselective Synthesis of Oligoamines via Buchwald-Hartwig Amination of (Hetero)Aryl Chlorides Employing Mor-DalPhos
Rational and Predictable Chemoselective Synthesis of Oligoamines via Buchwald-Hartwig Amination of (Hetero)Aryl Chlorides Employing Mor-DalPhos
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DOI：
10.1021/jo202358p
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发表时间：
2012-01-20
影响因子：
3.6
通讯作者：
Stradiotto, Mark
中科院分区：
文献类型：
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作者：
Tardiff, Bennett J.;McDonald, Robert;Stradiotto, Mark
我们报道了在合成二胺、三胺和四胺(62例)中用单一催化剂体系([Pd(肉桂基)氯](2)/L1；L1=N-(2-(di(1-adamantyl)phosphino)phenyl)morpholine，Mor-DalPhos)进行的Buchwald Hartwig胺化反应中合成有用的化学选择性的不同证明。竞争反应确定了该催化体系对胺偶联伙伴的以下相对偏好：线性伯烷基胺和亚胺>；无阻碍的富电子伯胺、伯肼、N，N-二烷基肼和环伯烷基胺>；无阻碍缺电子伯胺、α-支化的伯烷基胺、受阻的富电子伯胺>；>；环状和无环的仲二烷胺、仲烷/芳基和二芳胺、α、α-支化的伯烷基胺和伯胺。以63%的产率合成了新的异构体配体N-(4-(di(1-adamantyl)phosphino)phenyOmorpholine(p-MoR-DalPhos，L2)，并对其进行了结晶学表征，[Pd(肉桂基)氯](2)/L2催化剂体系表现出发散反应活性。将所建立的[Pd(肉桂基)氯](2)/L1的反应性趋势应用于二、三和四胺的化学选择性合成。2-(4-氨基苯基)乙胺与[Pd(肉桂基)氯](2)/L1和4-氯甲苯(生成5a)在伯烷基胺上发生了优先芳基化反应；当使用[Pd(肉桂基)氯](2)/L2时，得到了替代的区域异构体(5a‘)。这些观察结果与配位化学研究一致，即2-(4-氨基苯乙胺)通过伯胺部分与原位生成的[(L1)Pd(p-甲苯基)](+)片段结合，以72%的产率得到结晶学表征的加合物[(L1)Pd(p-甲苯基)(NH2 CH2CH2(4-C6H4NH2)]+OTF-(7))。
We report a diverse demonstration of synthetically useful chemoselectivity in the synthesis of di-, tri-, and tetraamines (62 examples) by use of Buchwald Hartwig amination employing a single catalyst system ([Pd(cinnamyl)Cl](2)/L1; L1 = N-(2-(di(1-adamantyl)phosphino)phenyl)morpholine, Mor-DalPhos). Competition reactions established the following relative preference of this catalyst system for amine coupling partners: linear primary alkylamines and imines > unhindered electron-rich primary anilines, primary hydrazones, N,N-dialkylhydrazines, and cyclic primary alkylamines > unhindered electron-deficient primary anilines, alpha-branched acyclic primary alkylamines, hindered electron-rich primary anilines >> cyclic and acyclic secondary dialkylamines, secondary alkyl/aryl and diarylamines, alpha,alpha-branched primary alkylamines, and primary amides. The new isomeric ligand N-(4-(di(1-adamantyl)phosphino)phenyOmorpholine (p-Mor-DalPhos, L2) was prepared in 63% yield and was crystallographically characterized; the [Pd(cinnamyl)Cl](2)/L2 catalyst system exhibited divergent reactivity. Application of the reactivity trends established for [Pd(cinnamyl)Cl](2)/L1 toward the chemoselective synthesis of di-, tri-, and tetraamines was achieved. Preferential arylation was observed at the primary alkylamine position within 2-(4-aminophenyl)ethylamine with [Pd(cinnamyl)Cl](2)/L1 and 4-chlorotoluene (affording 5a); the alternative regioisomer (5a') was obtained when using [Pd(cinnamyl)Cl](2)/L2. These observations are in keeping with coordination chemistry studies, whereby binding of 2-(4-aminophenypethylamine to the in situ generated [(L1)Pd(p-tolyl)](+) fragment occurred via the primary amine moiety, affording the crystallographically characterized adduct [(L1)Pd(p-tolyl)(NH2CH2CH2(4-C6H4NH2)]+OTf- (7) in 72% yield.