Guanidine Organocatalyst for the Asymmetric Mannich-Type Reaction between α-Isothiocyanato Imide and Sulfonyl Imines
Guanidine Organocatalyst for the Asymmetric Mannich-Type Reaction between α-Isothiocyanato Imide and Sulfonyl Imines
复制标题
DOI：
10.1002/chem.201002571
复制
发表时间：
2011-02-01
影响因子：
4.3
通讯作者：
Feng, Xiaoming
中科院分区：
文献类型：
--
作者：
Chen, Xiaohong;Dong, Shunxi;Feng, Xiaoming
Xiaohong Chen，Shunxi Dong，Zhen Qiao，Yin Zhu，Mingsheng Xie，Lili Lin，Xiaohua Liu，* and Xiaoming Feng*[a] α，β-Diamino acids are key structural components in many molecules，[1] such as biological active natural products and synthetic materials. [2]光学活性α，β-二氨基衍生物的制备方法多种多样。[3]这些方法大多集中在甘氨酸亚胺或硝基酯与各种亚胺的Mannich反应，这为构建这些化合物提供了直接和有利的方法。[4-6]近年来，α-异硫氰酸酰亚胺已被用作Mannich反应中的甘氨酸亚胺等价物。Willis及其同事报道了使用DBFox的手性镁络合物衍生物进行α-异硫氰酸酰亚胺与亚胺的曼尼希反应的第一个实例。[7a]Seidel和Zhong的研究小组都发现奎尼丁衍生物有机催化剂可以催化该反应，具有良好的对映体选择性和非对映体选择性。[7b尽管有这些优异的结果，但新催化剂体系的设计仍然是相当大的挑战。胍基由于具有高pKa值和双氢键等特性，在分子识别和生物催化中发挥着重要作用。[8]近年来，手性胍类化合物在不对称有机催化反应中已成为一个很有吸引力的目标化合物，并被证明是一种强有力的不对称反应试剂。[9-10]在此，我们介绍了一种易于制备的手性双胍有机催化剂，用于α-异硫氰酸酰亚胺与N-Ts-保护的亚胺的不对称Mannich型反应，该催化剂在温和条件下提供了优异的结果。最初，单胍1a被合成用于催化不对称Mannich型反应，因为它可以作为双功能催化剂。[9f]从苯甲醛衍生的α-异硫氰酸酰亚胺2和N-Ts-亚胺3获得中等结果（表1，条目1）。合成了一系列具有手性或非手性键的双胍以改善结果（方案1）。以苯二胺为原料合成的手性双胍1d比以（1 S，2S）-1，2-二苯基乙二胺和（1 S，2S）-1，2-环己烷二胺为原料合成的手性双胍1b和1c更具有上级的选择性，收率96%，dr> 95：5，ee 82（表1，条目4相对于条目2和3）;连接能够调节两个胍部分的空间排列以满足适当的不对称诱导。溶剂调查显示，使用CHCl 3作为共溶剂，可以获得具有最佳结果的加合物，94%产率，> 95：5 dr和89% ee（表1，条目5，详细信息，参见支持性信息）。
Xiaohong Chen, Shunxi Dong, Zhen Qiao, Yin Zhu, Mingsheng Xie, Lili Lin, Xiaohua Liu,* and Xiaoming Feng*[a] α, β-Diamino acids are key structural components in many molecules,[1] such as biologically active natural products and synthetic materials.[2] Various methods for the preparation of optically active α, β-diamino derivatives have been established.[3] Most of these approaches have focused on Mannich reactions of glycine imines or nitro esters with various imines, which provide a direct and favorable method for the construction of these compounds.[4–6] In recent years, α-isothiocyanato imides have been employed as glycine imine equivalents in Mannich reactions. Willis and co-workers reported the first example of a Mannich reaction of the α-isothiocyanato imide with imines using chiral magnesium complex derivatives from DBFox.[7a] Seidel s group and Zhong s group both found that quinidine-derived organocatalysts could catalyze the reaction with good diastereoselectivity and enantioselectivity.[7b, c] Despite these excellent results, the design of new catalyst systems remains a considerable challenge. The guanidine group plays important roles in molecular recognition and as a catalyst in biological systems owing to its characteristics, such as high pKa value and dual hydrogen-bonding.[8] Over the past few years, chiral guanidines have become an attractive target in asymmetric organocatalysis and have been shown to be powerful reagents for enantioselective reactions.[9–10] Herein, we present a readily prepared chiral bisguanidine organocatalyst for the asymmetric Mannich-type reaction of α-isothiocyanato imide with N-Ts-protected imines, which provides excellent results under mild conditions.Initially, monoguanidine 1a was synthesized to catalyze the asymmetric Mannich-type reaction because it could serve as a bifunctional catalyst.[9f] Moderate results were obtained from α-isothiocyanato imide 2 and N-Ts-imine 3 derived from benzaldehyde (Table 1, entry 1). A series of bisguanidines with a chiral or achiral linkage were synthesized to improve the outcomes (Scheme1). Chiral bisguanidine 1d derived from benzene-1, 3-diamine was superior to 1b and 1c derived from (1S, 2S)-1, 2-diphenylethylenediamine and (1S, 2S)-cyclohexane-1, 2-diamine, respectively, giving the desired product in 96% yield,> 95: 5 dr and 82% ee (Table 1, entry 4 vs. entries 2 and 3); the linkage was able to adjust the spatial arrangement of the two guanidine moieties to meet the proper asymmetric induction. A solvent survey revealed that adducts could be obtained with the best results, 94% yield,> 95: 5 dr and 89% ee using CHCl3 as cosolvent (Table 1, entry 5, for details, see Supporting Infor-