Acta Chimica Sinica ›› 2018, Vol. 76 ›› Issue (11): 878-882.DOI: 10.6023/A18100413 Previous Articles     Next Articles

Special Issue: 有机小分子-金属协同催化



李雪飞a, 林进顺a, 王建a, 李忠良b, 顾强帅b, 刘心元a   

  1. a. 南方科技大学化学系 深圳市格拉布斯研究所 深圳 518055;
    b. 南方科技大学 前沿与交叉科学研究院 深圳 518055
  • 投稿日期:2018-10-07 发布日期:2018-10-15
  • 通讯作者: 顾强帅, 刘心元;
  • 基金资助:


Cu/Chiral Phosphoric Acid-Catalyzed Asymmetric Radical-Initiated Aminoarylation of Alkenes

Li Xue-Feia, Lin Jin-Shuna, Wang Jiana, Li Zhong-Liangb, Gu Qiang-Shuaib, Liu Xin-Yuana   

  1. a. Department of Chemistry and Shenzhen Grubbs Institute, Southern University of Science and Technology, Shenzhen 518055;
    b. SUSTech Academy for Advanced Interdisciplinary Studies, Southern University of Science and Technology, Shenzhen 518055
  • Received:2018-10-07 Published:2018-10-15
  • Contact: 10.6023/A18100413;
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21722203, 21572096), the Shenzhen Special Funds (Nos. JCYJ20170412152435366, JCYJ20170307105638498) and the Shenzhen Nobel Prize Scientists Laboratory Project (No. C17213101).

Enantioenriched pyrrolidines bearing a β-aryl group and an α-quaternary carbon stereocenter are important structural motifs in many natural products and pharmaceuticals, and their enantioselective synthesis has thus received extensive attention over the last several decades. Nonetheless, so far as we know, asymmetric aminoarylation of alkenes to access such targets has only been independently reported by Wolfe and Liu using palladium catalysis involving a key aminopalladation step, and thus, general and practical methodologies towards a variety of chiral pyrrolidines are still in demand and highly desirable. As part of our ongoing interest in radical-initiated difunctionalization reactions of alkenes based on Cu(I)/chiral phosphoric acid (CPA) catalysis, we sought to develop a mechanistically distinct and complementary approach for this asymmetric palladium(Ⅱ)-catalyzed aminoarylation of alkenes. Herein we describe our efforts toward the development of the efficient asymmetric radical-initiated aminoarylation of alkenes with aryldiazonium salts enabled by Cu(I)/CPA catalysis. A general procedure for the aminoarylation of alkenes with aryldiazonium salts is as follows:under argon, an oven-dried resealable Schlenk tube equipped with a magnetic stir bar was charged with urea substrate 1 (0.1 mmol, 1.0 equiv.), CuI (1.9 mg, 0.01 mmol, 10 mol%), CPA[(S)-A1 (9.3 mg, 0.015 mmol, 15 mol%], aryldiazonium salts 2 (0.12 mmol, 1.2 equiv.), Na3PO4 (19.7 mg, 0.12 mmol, 1.2 equiv.) and isopropyl acetate(1.0 mL) at 32℃ and the sealed tube was then stirred under the same conditions. Upon completion (monitored by thin-layer chromatography), the reaction mixture was directly purified by silica gel chromatography[eluent:V(petroleum ether):V(EtOAc)=100:0 to 3:1] to afford the desired product 3. The enantiometric excess of product was determined by chiral high-performance liquid chromatography (HPLC) analysis. A broad scope of substrates worked well under this standard conditions to afford enantioenriched pyrrolidines in good yield with good to excellent enantioselectivity. A series of control experiments were conducted to determine the reaction mechanism as a radical process and a possible mechanism was proposed.

Key words: copper catalysis, chiral phosphoric acid, radical, aryldiazonium salts, asymmetric aminoarylation