Zheng Jia, Peters Bram B C, Mallick Rajendra K, Andersson Pher G
Department of Organic Chemistry, Stockholm University, 10691, Stockholm, Sweden.
The Marine Biomedical Research Institute, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang, 524023, China.
Angew Chem Int Ed Engl. 2025 Jan 15;64(3):e202415171. doi: 10.1002/anie.202415171. Epub 2024 Nov 6.
The concept of dual catalysis is an emerging area holding high potential in terms of preparative efficiency, yet faces severe challenges in compatibility of reaction conditions and interference of catalysts. The transition-metal catalyzed stereoselective hydrogenation of olefins and ketones typically proceeds under different reaction conditions and/or uses a different reductant. As a result, these two types of hydrogenations can normally not be performed in the same pot. Herein, the stereocontrolled hydrogenation of enones to saturated alcohols is described, enabled by orthogonal dual iridium catalysis, using molecular hydrogen for both reductions. In this one-pot procedure, N,P-iridium catalysts (hydrogenation active towards olefins) and NHC,P-iridium catalysts (hydrogenation active towards ketones) operated independently of one another allowing the construction of two contiguous stereogenic centers up to 99 % ee, 99/1 d.r. Ultimately, by simple selection of the chirality of either ligands, the enone could be efficiently reduced to all four stereoisomers of the saturated alcohol in equally high stereopurity. This degree of stereocontrol for the synthesis of different stereoisomers by dual transition-metal catalyzed hydrogenation was previously not attained. The generality in substituted enones (alkyl, aryl, heteroaryl) demonstrate the wide applicability of this concept.
双催化概念是一个新兴领域,在制备效率方面具有巨大潜力,但在反应条件的兼容性和催化剂的干扰方面面临严峻挑战。过渡金属催化的烯烃和酮的立体选择性氢化通常在不同的反应条件下进行和/或使用不同的还原剂。因此,这两种类型的氢化反应通常不能在同一反应釜中进行。本文描述了通过正交双铱催化将烯酮立体选择性氢化为饱和醇的反应,两种还原反应均使用分子氢。在这个一锅法过程中,N,P-铱催化剂(对烯烃具有氢化活性)和NHC,P-铱催化剂(对酮具有氢化活性)彼此独立起作用,能够构建两个相邻的立体中心,对映体过量值高达99%,非对映体比例为99/1。最终,通过简单选择任一配体的手性,烯酮可以高效地还原为饱和醇的所有四种立体异构体,且立体纯度同样高。通过双过渡金属催化氢化合成不同立体异构体时,此前尚未达到这样的立体控制程度。取代烯酮(烷基、芳基、杂芳基)的通用性证明了这一概念的广泛适用性。