摘要/Abstract

三组分双官能化反应是一种高效、简便构建C―C键、C―X键的方式. 双键广泛存在于众多有机化合物中, 对双键的双官能化反应研究有巨大的应用潜力. 本工作以Ni(COD)₂为催化剂, 以芳基溴化镁、芳基溴化物为芳基化试剂, 实现了3-芳基-2-丙烯醛亚胺中碳碳双键的双芳基化反应. 该反应建立了一个新的镍催化α,β-不饱和醛的α,β-双芳基化方法, 可以高度区域选择性地向底物分子中引入两个不同取代的芳环, 得到多种2,3,3-三芳基丙醛骨架的产物. 利用这一反应作为核心步骤实现了天然产物Quebecol的简便合成. 机理研究表明, 该反应可能经历了亲核加成、金属交换、还原消除的历程.
关键词: 双芳基化, α,β-不饱和醛, 醛亚胺, 镍催化, 三组分反应
Three-component difunctionalization reaction is one of the most important ways to construct C―C bond or C―X bond in organic chemistry. It has the characteristics of high efficiency by introducing two new chemical bonds into the substrate at the same time. Most current reports on the difunctionalization follow the interest of unsaturated bonds such as olefins. Olefins exist in many natural products and play an important role in organic synthesis, and they are widely used in pharmaceutical manufacture, chemical industry and experimental study. Therefore, the study on the difunctionalization reaction of olefins is of a great potential application. In this paper, we report an α,β-diarylation reaction of α,β-unsaturated ald- imines with Ni(COD)₂ as catalyst, and aryl magnesium bromides and aryl bromides as the arylating reagents. This method offers a new straightforward strategy to introduce two different aryls concurrently and provides a readily access to various triphenyl-substituted propionaldehydes. Moreover, the synthesis of natural product Quebecol (2,3,3-tri-(3-methoxy-4- hydroxyphenyl)propan-1-ol) can be realized by using the established reaction as the core step. Mechanistic studies revealed that the reaction underwent a process of nucleophilic addition, metal exchange and reductive elimination. A general procedure of this nickel-catalyzed diarylation is as follows: To a 25 mL Schlenk tube equipped with a magnetic stir bar were added an aldimine (0.20 mmol), aryl bromide (0.40 mmol), PPh₃ (0.04 mmol, 20 mol%) and Ni(COD)₂ (0.02 mmol, 10 mol%). After being evacuated and backfilled with nitrogen for three times, dry THF (1.6 mL) and aromatic Grignard reagent (0.4 mL, 1.0 mol/L in THF, 0.40 mmol) were added to the tube. The reaction mixture was stirred at 80 ℃ under an nitrogen atmosphere for 12 h and quenched with 3 mol/L HCl (aq.). The mixture was extracted with ethyl acetate (20 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel to afford the desired triphenyl-substituted propionaldehydes.
Key words: diarylation, α,β-unsaturated aldehyde, aldimine, nickel-catalysis, three-component reaction


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