Acta Chimica Sinica ›› 2014, Vol. 72 ›› Issue (7): 825-829.DOI: 10.6023/A14040319 Previous Articles     Next Articles

Special Issue: 不对称催化与合成



马世雄a, 钟源a, 王守磊a, 许兆青b, 常民a, 王锐a,b   

  1. a 兰州大学 生命科学学院 兰州 730000;
    b 兰州大学 甘肃省新药临床前研究重点实验室 兰州 730000
  • 投稿日期:2014-04-24 发布日期:2014-05-30
  • 通讯作者: 许兆青, 王锐;
  • 基金资助:

Organocatalyzed Asymmetric Allylic Alkylation of MBH-Carbonates with Pyrazolones

Ma Shixionga, Zhong Yuana, Wang Shouleia, Xu Zhaoqingb, Chang Mina, Wang Ruia,b   

  1. a School of Life Sciences, Lanzhou University, Lanzhou 730000;
    b Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou 730000
  • Received:2014-04-24 Published:2014-05-30
  • Supported by:
    Project supported by the National Natural Science Foundation of China (Nos. 21102141 and 21202072) and the Fundamental Research Funds for the Central Universities (Nos. 860976和861188).

The asymmetric allylic alkylation (AAA) reaction is one of the important transformations in asymmetric synthesis, which was intensively studied in the last decade. Recently, the use of Morita-Baylis-Hillman (MBH) carbonates as electrophiles for the AAA reaction has attracted much attention. Pyrazole is an important pharmacophore, which often exhibit various biological and pharmacological activities. In the last years, the asymmetric synthesis using pyrazolones as the nucleophiles were reported by several research groups. However, the work were mainly focused on the asymmetric conjugate addition of pyrazoles to α,β-unsaturated compounds, and other types of enantioselective reactions were seldom studied. Herein, we report the first example of AAA reaction of MBH carbonates using pyrazolones as nucleophiles. In the reaction, we found that different Lewis basic catalyst, namely PPh3 and DABCO, shown different regioselectivity: PPh3 gave the γ-selective product whereas DABCO led to a complete β-selectivity. During the catalyst screening, cinchonine gave the best result. The enantioselectivity heavily relied on the choice of solvent: MeOH was superior compared to EtOH, CH2Cl2, DCE, acetone, CH3CN, toluene, m-xylene and PhCl. In the substrate scope study, all the reactions were proceeded smoothly under mild conditions by using cinchonine as the catalyst (20 mol%) and give the β-selective allylic alkylation products with good yields (55%~91%) and high enantioselectivities (up to 93% ee). Based on our experimental results and previous reports, a preliminary mechanism of bifunctional catalysis was proposed. A representative procedure for the asymmetric allylic alkylation of MBH-carbonates with pyrazolones is as follows: to a flask equipped with a magnetic stirring bar was charged with pyrazolone 1 (0.1 mmol) and MBH-carbonate 2 (0.12 mmol) in methanol (2 mL), and then, the cinchonine catalyst (6 mg, 20 mol%) was added under air. The reaction solution was stirred at room temperature for 72 to 96 hours. Then, the mixture was concentrated and purified through a flash chromatography (silica gel, PE/EtOAc, V:V=7:1) to give the corresponding products 3.

Key words: organocatalysis, cinchonine, MBH carbonates, pyrazolone, asymmetric allylic alkylation