Department of Chemistry, Aarhus University, 8000, Aarhus, Denmark.
Chemistry. 2021 Dec 9;27(69):17465-17475. doi: 10.1002/chem.202103376. Epub 2021 Oct 21.
Results of an examination of the organocatalytic enantioselective α-chlorination of 2-phenylpropanal are described. Synthetic investigation including the screening of primary and secondary aminocatalysts, many different reaction conditions, and other α-branched aldehydes show that especially primary aminocatalysts can catalyze the formation of the α-chloro branched aldehydes in good yields, but only with moderate enantioselectivities. In order to try to understand the challenge in obtaining high enantioselectivity for the aminocatalytic α-chlorination of α-branched aldehydes a series of experimental investigations were performed employing 2-phenylpropanal as a model system. These investigations have been coupled with computational investigations, which provided important insight into the moderate enantioselectivity of this chlorination reaction. Analysis of the reaction showed, that the lack of control over the selectivity of formation of the (E)- and (Z)-enamine intermediate, and the clustering of reaction barriers of possible reaction pathways help to rationalize difficulties in producing high enantioselectivity.
描述了手性有机催化的 2-苯基丙醛的对映选择性α-氯化反应的结果。包括对伯胺和仲胺催化剂的筛选、许多不同反应条件和其他α-支链醛的合成研究表明，特别是伯胺催化剂可以很好地收率催化α-氯代支链醛的形成，但只有中等的对映选择性。为了尝试理解在手性有机催化α-氯化α-支链醛中获得高对映选择性的挑战，对 2-苯基丙醛进行了一系列的实验研究。这些研究与计算研究相结合，为该氯化反应的中等对映选择性提供了重要的见解。对反应的分析表明，对（E）-和（Z）-烯胺中间体形成的选择性控制的缺乏，以及可能反应途径的反应势垒的聚类有助于解释产生高对映选择性的困难。
