Cascade CuH-catalysed conversion of alkynes into enantioenriched 1,1-disubstituted products
Cascade CuH-catalysed conversion of alkynes into enantioenriched 1,1-disubstituted products
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DOI：
10.1038/s41929-019-0384-6
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发表时间：
2020-01-01
期刊：
影响因子：
37.8
通讯作者：
Engle, Keary M.
中科院分区：
文献类型：
--
作者：
Gao, De-Wei;Gao, Yang;Engle, Keary M.
烯烃和炔烃的加成是生产高官能化产品的有用途径。在这里，作者报道了通过CuH催化的不对称氢化/氢胺化反应使炔烃的1，1-去功能化。富含对映体的α-氨基硼酸在药物化学中发挥着独特的作用，并已成为蛋白酶体抑制剂中的特权药效团。此外，它们还代表了有机合成中有用的手性构件。近年来，CuH催化的不对称烯烃加氢功能化已成为构筑立体生碳中心的有力工具。相比之下，应用CUH级联催化来实现炔烃的还原1，1-去功能化仍然是一个重要的，但在很大程度上尚未解决的合成挑战。在此，我们报道了一种有效的合成α-氨基硼化合物的方法，该方法由CuH催化的氢化-硼氢化/氢胺化反应合成。值得注意的是，这种转化选择性地提供了所需的1，1-异双官能化产物，而不是替代的同双官能化、1，2-异双官能化或还原单官能化的副产物，从而提供了快速获得这些具有高化学、区域和对映体选择性的特权支架的途径。
Additions to alkenes and alkynes are useful routes for generating highly functionalized products. Here the authors report the 1,1-difunctionalization of alkynes through a CuH-catalysed asymmetric hydroboration/hydroamination cascade.Enantioenriched alpha-aminoboronic acids play a unique role in medicinal chemistry and have emerged as privileged pharmacophores in proteasome inhibitors. Additionally, they represent synthetically useful chiral building blocks in organic synthesis. Recently, CuH-catalysed asymmetric alkene hydrofunctionalization has become a powerful tool to construct stereogenic carbon centres. By contrast, applying CuH cascade catalysis to achieve the reductive 1,1-difunctionalization of alkynes remains an important, but largely unaddressed, synthetic challenge. Herein, we report an efficient strategy to synthesize alpha-aminoboron compounds by a CuH-catalysed hydroboration/hydroamination cascade of readily available alkynes. Notably, this transformation selectively delivers the desired 1,1-heterodifunctionalized product rather than the alternative homodifunctionalized, 1,2-heterodifunctionalized or reductively monofunctionalized by-products, thereby offering rapid access to these privileged scaffolds with high chemo-, regio- and enantioselectivity.