Cu(OTf)₂ Catalyzed Conjugate Addition of Mercaptans to Enones

Abstract

Thioether is a class of compounds with important biological and physiological activities, especially for drugs and natural products, and its efficient synthesis method is one of the research hotspots in organic chemistry. Thia-Michael addition, especially the addition catalyzed by small organic molecules has been widely proved to be an effective method for synthesizing thioether molecules. However, very few studies on transition metal-catalyzed thia-Michael addition have been published and further exploration in this area is needed. In this work, different types of thiol molecules have been effectively added to various cyclic and linear Michael acceptors through the catalysis of copper(II) triflate. To our delight, 42 kinds of sulfide molecules (up to 99% yield) have been efficiently synthesized. This method has many advantages such as mild reaction conditions, wide substrates, simple operation and excellent yield, providing a new method for the preparation of various thioether molecules. Keywords copper catalysis; conjugate addition; mercaptan 硫醚分子在自然界中广泛存在, 具有重要的生物生 理活性 [1] , 是药物分子设计中一种富有价值的分子工 具 [2] , 广泛应用于香精香料的制作过程 [3] , 其合成研究 对于新型药物和香精香料等的研发具有重要意义.硫-迈克尔加成反应特别是通过有机小分子催化的 硫-迈克尔加成反应是合成 γ-羰基硫醚的一种有效手段, 国内的科研工作者在这一领域做出了重要贡献 [4][5][6][7][8][9][10] , 其 通过多类小分子催化体系实现了硫醇与烯酮、硝基烯 烃、不饱和酯等多类迈克尔受体的手性加成或者外消旋 加成. 其中包括但不限于肖文精 [4] 、 陈甫雪 [5] 和王春江课 题组 [6] 报道的硫脲分子催化剂, 何林 [7] 和黄湧课题组 [8] 提出的卡宾小分子催化体系, 江智勇 [9] 和杜大明课题 组 [10] 构建的四方酰胺催化体系等. 国外的 Wang [11] 、 Singh [12][13] 、Dixon [14] 、Johnson [15] 、Ender [16] 、Takemoto 课题组 [17] 等也在小分子催化的硫醇对迈克尔受体的共 轭加成反应中做出了重要贡献. 与小分子催化的硫醇对迈克尔受体的共轭加成反 应相比, 有关过渡金属催化的共轭加成反应的报道则较 少 [18] , 部分原因是硫原子对金属催化剂有毒化作用, 导 致催化反应难以进行. 目前, 过渡金属催化的手性加成 反应仅有几例的报道, 如 White 课题组 [19] 的铁金属催化 体系、Vaccaro 课题组 [20] 的钪金属催化体系、龚磊课题

NBS-mediated elimination of β-keto sulfides to access enones and dienones

“…Many facile and efficient thia-Michael additions have been widely reported using thiols as nucleophiles to attack Michael acceptors in the past decades. 1–4 Generally, four different pathways have been studied, including organocatalysis, 1 transition metal catalysis, 2 methods in the water phase, 3 and heterogeneous catalysis. 4 However, few studies on the reverse reaction of the thia-Michael addition have been published because of the poor leaving ability of alkylthio groups.…”