化学
烷基
对映选择合成
电泳剂
氢化物
亲核细胞
组合化学
镍
有机化学
催化作用
金属
作者
Srikrishna Bera,Runze Mao,Xile Hu
出处
期刊:Nature Chemistry
[Springer Nature]
日期:2020-12-30
卷期号:13 (3): 270-277
被引量:129
标识
DOI:10.1038/s41557-020-00576-z
摘要
Cross-coupling of two alkyl fragments is an efficient method to produce organic molecules rich in sp3-hybridized carbon centres, which are attractive candidate compounds in drug discovery. Enantioselective C(sp3)–C(sp3) coupling is challenging, especially of alkyl electrophiles without an activating group (aryl, vinyl, carbonyl). Here, we report a strategy based on nickel hydride addition to internal olefins followed by nickel-catalysed alkyl–alkyl coupling. This strategy enables the enantioselective cross-coupling of non-activated alkyl halides with alkenyl boronates to produce chiral alkyl boronates. Employing readily available and stable olefins as pro-chiral nucleophiles, the coupling proceeds under mild conditions and exhibits broad scope and high functional-group tolerance. Applications for the functionalization of natural products and drug molecules, as well as the synthesis of chiral building blocks and a key intermediate to (S)-(+)-pregabalin, are demonstrated. Methods for producing organic molecules rich in sp3-hybridized carbon centres can be particularly useful for drug development. Now, it has been shown that the enantioselective cross-coupling of non-activated alkyl halides with alkenyl boronates enables the synthesis of chiral alkyl boronates. The reaction proceeds via nickel hydride insertion into an internal alkene followed by nickel-catalysed alkyl–alkyl cross-coupling.
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