通过NiH催化获得季α -氰基羰基化合物的模块化途径。

IF 8.7 Q1 CHEMISTRY, MULTIDISCIPLINARY
JACS Au Pub Date : 2025-08-21 eCollection Date: 2025-09-22 DOI:10.1021/jacsau.5c00835
Yoonho Lee, Yujin Jung, Seonhwa Choo, Kwangmin Shin
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引用次数: 0

摘要

季α-氰基羰基化合物是有机合成中一类重要的分子,因为它们可以作为基本结构单元的前体,并在药物合成中具有潜在的应用前景。尽管这些空间拥挤和高度功能化的结构很重要,但开发通用和实用的合成平台仍然是一个持续的挑战。本文报道了一种由镍氢化物催化的α,β-不饱和腈与酰基氟化物及其氨基甲酰和甲酰基衍生物的加氢功能化反应。该合成方案能够在温和的条件下模块化合成各种各样的季α-氰基羰基化合物,包括酮类、酰胺类和酯类,不需要外部配体。综合DFT和实验机理研究表明,目前的NiH催化是通过区域选择性加氢金属化进行的,然后通过重排形成镍-酮烯酸盐中间体,随后镍-酮烯酸盐与羰基氟化物之间发生亲核取代反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Modular Access to Quaternary α‑Cyano Carbonyl Compounds via NiH Catalysis.

Quaternary α-cyano carbonyl compounds are an important class of molecules in organic synthesis due to their versatility as precursors to essential building blocks and their potential applications in pharmaceutical synthesis. Despite the importance of these sterically congested and highly functionalized structures, the development of a general and practical synthetic platform remains a persistent challenge. Herein, we report a nickel-hydride-catalyzed hydrofunctionalization of α,β-unsaturated nitriles with acyl fluorides as well as their carbamoyl and formyl derivatives. This synthetic protocol enables the modular synthesis of a diverse range of quaternary α-cyano carbonyl compounds, including ketones, amides, and esters, under mild conditions and without the need for an external ligand. Combined DFT and experimental mechanistic studies reveal that the present NiH catalysis proceeds via regioselective hydrometalation, followed by the formation of a nickel-keteneiminate intermediate through rearrangement and subsequent nucleophilic substitution reaction between the nickel-keteneiminate and the carbonyl fluorides.

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来源期刊
CiteScore
9.10
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