BippyPhos: A Single Ligand With Unprecedented Scope in the Buchwald-Hartwig Amination of (Hetero) aryl Chlorides
BippyPhos: A Single Ligand With Unprecedented Scope in the Buchwald-Hartwig Amination of (Hetero) aryl Chlorides
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DOI：
10.1002/chem.201302453
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发表时间：
2013-12-02
影响因子：
4.3
通讯作者：
Stradiotto, Mark
中科院分区：
文献类型：
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作者：
Crawford, Sarah M.;Lavery, Christopher B.;Stradiotto, Mark
在过去的二十年里，人们对钯催化胺的芳基化反应和相关的含NH底物(即Buchwald-Hartwig胺化)的新配体的开发给予了相当大的关注。由学术界和工业界的研究小组产生的结构多样化的配体，促进了空间和电子上不同的底物的调节，包括氨、肼、胺、酰胺和NH杂环。尽管取得了这些成就，但催化剂通用性方面的问题仍然存在，需要获得多个配体来容纳所有这些含NH的底物。为了解决这一重大限制，我们确定了BippyPhos/[Pd(肉桂基)氯](2)催化剂体系能够在中到低催化剂载量下催化各种官能化(杂化)芳基氯以及溴化物和对甲苯磺酸盐的胺化反应。这里描述的成功的转化包括伯胺和仲胺、NH杂环、酰胺、氨和联氨，从而展示了在单一Pd/配体催化剂体系中所报道的含NH偶联伙伴的最大范围。我们还确定了BippyPhos/[Pd(肉桂基)氯](2)是金属催化(杂环)芳基氯化物与NH吲哚交叉偶联的最广泛的底物范围。此外，利用BippyPhos/[Pd(肉桂基)氯](2)对氨的选择性单芳化和吲哚的N-芳基化反应的催化作用，开发了一种新的一锅两步法合成N-芳基杂环化合物。虽然含NH偶联对的范围很广，但BippyPhos/[Pd(肉桂基)氯](2)也表现出显著的选择性，该选择性被用于底物的化学选择性单芳基化反应，该底物具有两个不同的含NH部分。
Over the past two decades, considerable attention has been given to the development of new ligands for the palladium-catalyzed arylation of amines and related NH-containing substrates (i.e., Buchwald-Hartwig amination). The generation of structurally diverse ligands, by research groups in both academia and industry, has facilitated the accommodation of sterically and electronically divergent substrates including ammonia, hydrazine, amines, amides, and NH heterocycles. Despite these achievements, problems with catalyst generality persist and access to multiple ligands is necessary to accommodate all of these NH-containing substrates. In our quest to address this significant limitation we identified the BippyPhos/[Pd(cinnamyl)Cl](2) catalyst system as being capable of catalyzing the amination of a variety of functionalized (hetero)aryl chlorides, as well as bromides and tosylates, at moderate to low catalyst loadings. The successful transformations described herein include primary and secondary amines, NH heterocycles, amides, ammonia and hydrazine, thus demonstrating the largest scope in the NH-containing coupling partner reported for a single Pd/ligand catalyst system. We also established BippyPhos/[Pd(cinnamyl)Cl](2) as exhibiting the broadest demonstrated substrate scope for metal-catalyzed cross-coupling of (hetero)aryl chlorides with NH indoles. Furthermore, the remarkable ability of BippyPhos/[Pd(cinnamyl)Cl](2) to catalyze both the selective monoarylation of ammonia and the N-arylation of indoles was exploited in the development of a new one-pot, two-step synthesis of N-aryl heterocycles from ammonia, ortho-alkynylhalo(hetero)arenes and (hetero) aryl halides through tandem N-arylation/hydroamination reactions. Although the scope in the NH-containing coupling partner is broad, BippyPhos/[Pd(cinnamyl)Cl](2) also displays a marked selectivity profile that was exploited in the chemoselective monoarylation of substrates featuring two chemically distinct NH-containing moieties.