Ni-Catalysed Regioselective α,β-Diarylation of α,β-Unsaturated Aldehydes

Abstract

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 aldimines 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-4hydroxyphenyl)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.