Synthesis of a New Chiral Organocatalysts and its Application in Asymmetric Morita-Baylis-Hillman Reaction

Rapid Communication

Austin J Anal Pharm Chem. 2018; 5(3): 1107.

Synthesis of a New Chiral Organocatalysts and its Application in Asymmetric Morita-Baylis-Hillman Reaction

Yu Qiuhan, Lu Weiwen, Ding Zhiqiang, Wei Min and Dai Zhenya*

Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 210009 Nanjing, P. R. China

*Corresponding author: Dai Zhenya, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 210009 Nanjing, P. R. China

Received: September 18, 2018; Accepted: October 09, 2018; Published: October 16, 2018

Introduction

The Morita–Baylis–Hillman (MBH) reaction was an organocatalyzed chemical transformation that provided effective and atom economical carbon–carbon bond-forming reactions [1-5]. Formally, this reaction promoted condensation between α-position of an electron-deficient alkene and the sp2 carbon atom of an aldehyde catalyzed by nucleophilic bases such as DABCO [5]. With highly functionalized MBH adducts and their derivatives, structurally complex and diverse molecules (such as acaterin, asmarines A and B, borrelidin, PPAPs and so many natural products [4,6]) could be easily achieved. Hence, the development of the MBH reaction has attracted considerable interest in recent years. However, several disadvantages such as poor conversions, low reaction rates, low enantioselectivity and the lack of definite mechanism also limited the applicability of the MBH reactions [2,4,6,7]. Therefore, it is important to investigate new catalytic system to solve known problems.

Results and Discussion

For the asymmetric MBH reaction, thiourea derivatives were widely used {7-12]. Besides, cyclohexanediamine and proline were both important chiral frameworks. Therefore, we combined these two structural units and synthesized a new catalyst C (Figure 1, Table 1).

In comparison to DABCO, there was no product when the reaction was carried out with DMAP as base. Meanwhile, the yield with DBU as base was much lower though DBU played an important role in the MBH reaction [13].

For further optimization, the effect of the solvents on the reaction was also investigated (Table 2).

Obviously, for this reaction, the presence of solvent exerted a tremendous influence.

Therefore, in order to get superior yields, DABCO should be used as the base while DCM should be chosen as the solvent.

According to the best condition we got above, many other reactions had been tested. Besides, optical rotation also had tested, and from Table 3, we could see that the selectivity of the catalyst was not satisfying. Thus further work should be done to improve the enantioselectivity of the reaction.