Nature Communications ( IF 14.7 ) Pub Date : 2024-05-21 , DOI: 10.1038/s41467-024-48737-9
Chunyang Zhao 1 , Rongwan Gao 2 , Wenxuan Ma 1 , Miao Li 1 , Yifei Li 1 , Qian Zhang 1 , Wei Guan 2 , Junkai Fu 1
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The dehydrogenation adjacent to an electron-withdrawing group provides an efficient access to α,β-unsaturated compounds that serving as versatile synthons in organic chemistry. However, the α,β-desaturation of aliphatic imines has hitherto proven to be challenging due to easy hydrolysis and preferential dimerization. Herein, by employing a pre-fluorination and palladium-catalyzed dehydrogenation reaction sequence, the abundant simple aliphatic amides are amendable to the rapid construction of complex molecular architectures to produce α,β-unsaturated imines. Mechanistic investigations reveal a Pd(0)/Pd(II) catalytic cycle involving oxidative H–F elimination of N-fluoroamide followed by a smooth α,β-desaturation of the in-situ generated aliphatic imine intermediate. This protocol exhibits excellent functional group tolerance, and even the carbonyl groups are compatible without any competing dehydrogenation, allowing for late-stage functionalization of complex bioactive molecules. The synthetic utility of this transformation has been further demonstrated by a diversity-oriented derivatization and a concise formal synthesis of (±)-alloyohimbane.
中文翻译:
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通过钯催化脱氢轻松合成 α,β-不饱和亚胺
邻近吸电子基团的脱氢提供了一种有效获得α , β-不饱和化合物的途径,这些化合物在有机化学中用作通用合成子。然而,由于容易水解和优先二聚化,脂肪族亚胺的α , β-去饱和迄今为止已被证明具有挑战性。在此,通过采用预氟化和钯催化脱氢反应序列,丰富的简单脂肪族酰胺可用于快速构建复杂的分子结构以产生α , β-不饱和亚胺。机理研究揭示了 Pd(0)/Pd(II) 催化循环,涉及N-氟酰胺的氧化 H-F 消除,然后原位生成的脂肪族亚胺中间体顺利进行α 、 β-去饱和。该方案表现出优异的官能团耐受性,甚至羰基也能兼容,无需任何竞争性脱氢,从而允许复杂生物活性分子的后期功能化。通过面向多样性的衍生化和 (±)-alloyohimbane 的简明形式合成,进一步证明了这种转化的合成效用。