“The Asymmetric Synthesis & Catalysis Group” in Central China Normal University was founded by Prof. Dr. Xiao in September, 2003 when he returned from the States. In the past decade, the group focused on the fundamental research on the development of “green” strategies for efficient construction of various carbo- and heterocyclic architectures. The group has developed a series of methodologies to achieve this goal though the innovation of concepts and methods, design and development of new reagents, reactions, catalysts and catalytic systems. These strategies have been demonstrated to be successful and powerful tools in the construction of complex and useful organic molecules, as well as in the concise synthesis of natural products, pharmaceuticals and their analogs. Over the past ten years, we have also trained 16 PhD and 20 master students. Now, the group consists of a professor, an associate professor and an assistant professor, together with 10 PhD students and 20 master students. More importantly, an innovative research team has been established featuring reasonable personnel structure, active scientific thinking and enthusiastic work in the field of chemical synthesis and catalysis.
1.Visible-Light Promoted Photoredox Transformations of Tunable Radicals and Their Synthetic Applications
Sunlight is an inexpensive, nonpolluting, abundant and endlessly renewable source of clean energy. It is of great importance to study the visible-light promoted photoredox transformations of tunable radicals and their synthetic applications in natural products and pharmaceuticals. In 2011, the Xiao group has developed the visible-light-induced oxidation/[3+2] cycloaddition/oxidative aromatization sequence to construct pyrrolo[2,1-a]isoquinolines, which are widely found in lamellarin alkaloids. The similar strategy has also been utilized in the synthesis of tetrahydroimidazoles via intramolecular cyclization reactions of diamines. Subsequently, the first visible-light induced aerobic oxidative hydroxylation of arylboronic acids to phenols has been realized by using molecular oxygen as the ultimate oxidant. More recently, they also developed an aerobic oxyamidation of indoles by the photocatalytic strategy for preparation of various tetrahydro-5H-indolo-[2,3-b]quinolinols. These papers have attracted much attention around the world (Chem. Rev. 2013, 113, 5322-5363; Eur. J. Org. Chem. 2012, 3359-3372), and two invited reviews have been published in Angew. Chem. Int. Ed. (2012, 51, 6828-6838) and Eur. J. Org. Chem (2013, 6755-6770), respectively.
可见光是一种清洁的、可再生的自然资源。研究可见光照射下、光氧化还原催化剂催化的可控自由基反应及其在药物分子和天然产物合成中的应用具有重要的理论意义和应用前景。近几年来，本研究组设计了一类新型的可见光诱导的氧化/[3+2]环加成/芳构化串联反应，并将这一反应成功应用于Lamellarin生物碱的核心骨架Pyrrolo[2,1-a]isoquinolines的构建。该策略也为天然产物Lamellarin家族的全合成提供了新的思路。另外，本研究组还利用可见光光氧化还原催化策略实现了分子内二胺的氧化环化反应，成功构建了一系列手性的四氢咪唑类化合物。同时，本研究组还在国际上首次实现了可见光诱导的芳基硼酸的氧化羟基化反应，该反应将可见光和氧气这两种绿色资源结合到同一反应体系当中，并以空气中的氧作为最终的氧化剂合成了一系列的苯酚及其类似物。最近，本研究小组还实现了可见光引发的吲哚衍生物的氧胺化反应，以中等到较高的产率构建了高度官能化的tetrahydro-5H-indolo [2,3-b]quinolinols。这些研究工作发表以后，得到了国内外同行的广泛关注，肖文精教授等应邀在国际权威学术期刊Angew. Chem. Int. Ed (2012, 51, 6828-6838)和Eur. J. Org. Chem (2013, 6755-6770)上撰写相关综述。
2.Development of New Reactions Involving Sulfur Ylides and New Reagents for the Construction of Carbo- and Heterocyclic Compounds
Sulfur ylides, acting as nucleophiles but bearing a leaving group, have served as dipole-type reagents and show great potential for the development of cascade reaction. The Xiao group has uncovered an unprecedented reaction of stable sulfur ylides and nitroolefins sequentially catalyzed by thiourea and DMAP to afford diverse and structurally complex oxazolidin-2-ones with high diastereoselectivities. Furthermore, a novel [4+1]/[3+2] cycloaddition cascade was successfully designed according to the rational incorporation of two different dipolarophiles in a single molecule. Another formal [4+1] annulations involving sulfur ylides have also been developed by this group to construct carbo- and heterocyclic compounds. Base on the success in sulfur ylides, Prof. Xiao and co-workers have been invited to review their related cascade reaction in Acc. Chem. Res. (2012, 45, 1278-1293)
硫叶立德作为一种带有离去基团的特殊亲核试剂，为串联反应的设计和发展提供了非常广阔的空间。本研究组以硝烃烯烃和硫叶立德为原料，以硫脲和N, N-二甲基吡啶为催化剂，发展了一个新的串联环化反应，从而实现了从简单原料出发，高度简捷、高非对映选择性地合成了一系列结构多样的噁唑啉-2-酮。同时，还设计并合成了一类具有双缺电子组分的新反应试剂，实现了硫叶立德与新试剂的分子间[4+1]/分子内[3+2]的串联环化反应。另外，还发展了一系列基于硫叶立德试剂的形式[4+1]环化反应，为一系列复杂的、具有潜在生物活性的碳/杂环分子的合成提供了新的合成方法。基于在这些方面的系列工作，肖文精教授等应邀在国际著名评述性期刊Acc. Chem. Res. (2012, 45, 1278-1293)上撰写个人评述。
3.Design of Tunable and Bifunctional Organocatalysts and Their Applications in Enantioselective Desymmetrization
It is of great importance to develop new catalysts and catalytic systems to improve the reaction efficiency and selectivity. Considerable attention has been directed toward this research field. The Xiao group has developed the organocatalytic dual activation concept that simultaneously increases the reactivity of nucleophilic and electrophilic reagents to provide an environment for better stereocontrol. These bifunctional organocatalysts have exhibited broad applicability in the enantioselective desymmetrization of carbo- and heterocyclic compounds. The related papers have attracted much attention and some of them were commented and cited in《Enantioselective Organocatalysis》(Edited by Peter I. Dalko, Wiley-VCH, 2007) and 《Stereoselective Organocatalysis》(Edited by Romon Rovis Terroes, Wiley-VCH, 2013）.
新型催化剂和催化体系的设计和发展对提高有机合成反应的效率和选择性具有极其重要的意义，已经成为有机合成化学研究中的永恒主题之一。基于有机催化剂廉价易制备、反应操作简单等优点，本研究组设计合成了一系列具有自主知识产权的双功能有机催化剂。这些催化剂被成功应用于不对称的Aldol、Michael加成反应，实现了碳/杂环体系的对映选择性去对称化。与此同时，我们也将三级胺—氢键双功能有机催化剂应用于不对称的双Michael加成反应、Morita–Baylis–Hillman和Michael-Aldol 串联反应，高化学选择性、立体选择性的合成得到了多取代的色滿、硫代色滿、色烯和四氢噻吩螺氧化吲哚等重要杂环化合物。这些工作得到了国内外同行的广泛关注，并应邀在Synlett上撰写一篇综述“Dual Activation in Organocatalysis: Design of Tunable and Bifunctional Organocatalysts and Their Applications in Enantioselective Reactions”（ Synlett, 2012, 490-508）总结这部分工作。而且，部分研究工作已经被写入《Enantioselective Organocatalysis》（Edited by Peter I. Dalko, Wiley-VCH, 2007）和《Stereoselective Organocatalysis》（Edited by Romon Rovis Terroes, Wiley-VCH, 2013）等学术专著。
4.Asymmetric Synthesis of Fused or Spiro-indole Derivatives Based on The Design of Cascade Reaction
Polycyclic indoles belong to an important class of nitrogen-containing heterocycles, which were first derived from organic bases in the field of biology. Several natural products and therapeutic agents possessing this heterocyclic motif exhibit remarkable biological and pharmacological activities. As a consequence, the polycyclic indole scaffold is regarded as the“privileged” structural motif for discovering novel medicinally relevant compounds. The chemical synthesis of these core structures has drawn extensive interests from synthetic community. Cascade reactions can provide an advantageous route to the highly efficient construction of various compounds on the basis of its several distinguishing feature, such as without separation of intermediates, simple operation and environmentally benign. Based on this effective strategy, our group has developed many types of cascade reactions, and a variety of tetrahydrocarbolines, tetrahydropyrano[3,4-b]indoles and tetrahydrocarbazoles have been successfully synthesized in a highly efficient and selective manner. As a derivative of indole, oxindole moiety is also widely found in a broad range of bioactive natural isolates and pharmaceutically important compounds, which exhibited antitumor and antibacterial activities. Various spirooxindoles bearing a quaternary stereocenter at C-3 position, such as oxindole with Cγ-tetrasubstituted α-amino acid, spirooxindole–tetrahydrothiophenes and bispirooxindole derivatives, have also been synthesized in a highly enantioselective manner using the same strategy by our group. These achievements have attracted considerable attention around the world after publication.
多环吲哚骨架和氧化吲哚骨架不仅广泛存在于许多有机碱类天然产物，而且还被认为是发现新型药物先导分子的“优势结构”。因此，其化学合成一直吸引着化学家们的广泛研究兴趣。本研究小组发展了多种操作简便、环境友好的串联反应，高效，高选择性地合成了四氢咔啉、吲哚骈四氢吡喃、四氢咔唑等一系列多环吲哚衍生物，以及氧化吲哚Cγ-四取代的α-氨基酸衍生物、氧化吲哚螺四氢噻吩、双螺环氧化吲哚衍生物等。与此同时，本研究组还利用该策略立体选择性及原子经济性地构建了色满和四氢喹啉等结构单元。这些工作发表后，受到了国内外同行的广泛关注，并应邀在两部学术专著《Catalytic Asymmetric Friedel-Crafts Alkylations》 (Wiley-VCH, 2009)和《Modern Approaches to the Synthesis of O- and N-heterocycles》(Research Signpost, 2007)中撰写了部分章节。