Trifluoromethylation of arenes and heteroarenes by means of photoredox catalysis

Modern drug discovery relies on the continual development of synthetic methodology to address the many challenges associated with the design of new pharmaceutical agents. One such challenge arises from the enzymatic metabolism of drugs in vivo by cytochrome P450 oxidases, which use single-electron oxidative mechanisms to rapidly modify small molecules to facilitate their excretion. A commonly used synthetic strategy to protect against in vivo metabolism involves the incorporation of electron-withdrawing functionality, such as the trifluoromethyl (CF(3)) group, into drug candidates. The CF(3) group enjoys a privileged role in the realm of medicinal chemistry because its incorporation into small molecules often enhances efficacy by promoting electrostatic interactions with targets, improving cellular membrane permeability, and increasing robustness towards oxidative metabolism of the drug. Although common pharmacophores often bear CF(3) motifs in an aromatic system, access to such analogues typically requires the incorporation of the CF(3) group, or a surrogate moiety, at the start of a multi-step synthetic sequence. Here we report a mild, operationally simple strategy for the direct trifluoromethylation of unactivated arenes and heteroarenes through a radical-mediated mechanism using commercial photocatalysts and a household light bulb. We demonstrate the broad utility of this transformation through addition of CF(3) to a number of heteroaromatic and aromatic systems. The benefit to medicinal chemistry and applicability to late-stage drug development is also shown through examples of the direct trifluoromethylation of widely prescribed pharmaceutical agents.     

利用相转移催化合成乙酸苄酯

利用相转移催化剂催化三水合乙酸钠和苄基氯的酯化反应，合成乙酸苄酯，产率为６５～９０％，酯含量在９８％以上。     

Total synthesis of marine natural products without using protecting groups

The field of organic synthesis has made phenomenal advances in the past fifty years, yet chemists still struggle to design synthetic routes that will enable them to obtain sufficient quantities of complex molecules for biological and medical studies. Total synthesis is therefore increasingly focused on preparing natural products in the most efficient manner possible. Here we describe the preparative-scale, enantioselective, total syntheses of members of the hapalindole, fischerindole, welwitindolinone and ambiguine families, each constructed without the need for protecting groups--the use of such groups adds considerably to the cost and complexity of syntheses. As a consequence, molecules that have previously required twenty or more steps to synthesize racemically in milligram amounts can now be obtained as single enantiomers in significant quantities in ten steps or less. Through the extension of the general principles demonstrated here, it should be possible to access other complex molecular architectures without using protecting groups.     

键联法合成高分子负载金属卟啉催化剂的研究进展

高分子负载金属卟啉有望提高金属卟啉的催化活性和稳定性，能有效地与产物分离，因此成为研究的热门课题．综述了近年来以静电作用、轴向配位和共价键合成高分子负载金属卟啉催化剂的研究进展．以金属卟啉单体与其他单体共聚合成高分子负载金属卟啉催化荆有望成为新的热门课题．     

相转移催化合成邻苯二甲酸丁苄酯的研究

本文采用四丁基溴化铵、聚乙二醇和β-环糊精作为相转移催化剂合成增塑剂邻苯二甲酸丁苄酯,研究了在无水碳酸钠及氢氧化钠水溶液中催化剂用量与增塑剂产率的关系,发现β-环糊精具有相转移催化酯化作用。     

相转移催化法合成苯乙醚的工艺研究

研究了在相转移催化剂四丁基溴化铵的催化下苯酚与溴乙烷反应生成苯乙醚的新方法。实验证明,该方法具有操作简便、反应时间短、不需要特殊试剂、三废少等特点。     

氧化石墨烯催化苯乙烯双羟化合成苯基乙二醇

以过氧化氢为氧化剂,研究Hummers法制得的氧化石墨,催化苯乙烯双羟化合苯基乙二醇,产物结构通过1 H NMR、13 C NMR、FT-IR和ESI-MS确认.考察不同反应温度、溶剂、氧化剂用量、催化剂用量及时间对反应收率的影响.结果表明,在45℃下,以水作为反应溶剂时,H2O2(30%)用量为10mmol,催化剂用量为100mg/mmol底物,反应时间18h,苯乙烯的转化率达到42%,苯基乙二醇的收率可达13%.催化剂循环使用5次,其催化活性未见明显下降.     

PbO均相催化反应精馏合成碳酸二苯酯的研究

通过对碳酸二甲酯(DMC)与苯酚(PhOH)酯交换法反应精馏合成碳酸二苯酯(DPC)的研究，筛选合适的催化剂和寻找最佳的工艺条件，为将来DPC的工业化打下基础。实验结果表明：在常压下，温度110～195℃范围内，当原料配比n(PhOH)：n(DMC)=2：1，n(PhOH)：n(催化剂)=1：0．016，反应时间10h，碳酸二甲酯转化率为32．63％(mol)，DPC产率为25．01％(mol)，碳酸苯甲酯(MPC)产率为7．62％(mol)，DPC的选择性为76．65％，且无苯甲醚生成。所选催化剂PbO的催化性能明显优于路易斯酸和二丁基二月桂酸锡。     

Synthesis of macrocyclic natural products by catalyst-controlled stereoselective ring-closing metathesis

Many natural products contain a C = C double bond through which various other derivatives can be prepared; the stereochemical identity of the alkene can be critical to the biological activities of such molecules. Catalytic ring-closing metathesis (RCM) is a widely used method for the synthesis of large unsaturated rings; however, cyclizations often proceed without control of alkene stereochemistry. This shortcoming is particularly costly when the cyclization reaction is performed after a long sequence of other chemical transformations. Here we outline a reliable, practical and general approach for the efficient and highly stereoselective synthesis of macrocyclic alkenes by catalytic RCM; transformations deliver up to 97% of the Z isomer owing to control induced by a tungsten-based alkylidene. Utility is demonstrated through the stereoselective preparation of epothilone C (refs 3-5) and nakadomarin A (ref. 6), the previously reported syntheses of which have been marred by late-stage, non-selective RCM. The tungsten alkylidene can be manipulated in air, delivering the products in useful yields with high stereoselectivity. As a result of efficient RCM and re-incorporation of side products into the catalytic cycle with minimal alkene isomerization, desired cyclizations proceed in preference to alternative pathways, even under relatively high substrate concentration.     

有机锡均相催化反应蒸馏合成碳酸二苯酯

通过对碳酸二甲酯(DMC)与苯酚酯交换法反应蒸馏合成碳酸二苯酯(DPC)的研究,筛选合适的催化剂和寻找最佳的工艺条件,为DPC的工业化打下基础。实验结果表明,在常压下,温度145℃,原料配比n(PhOH)∶n(DMC)=3∶1,n(PhOH)∶n(催化剂)=1∶0.012,反应时间10h,碳酸二甲酯总转化率为32.04%,DPC产率为18.00%,碳酸苯甲酯(MPC)产率为14.04%,DPC的选择性为56.18%,而且无苯甲醚和CO2生成,所选催化剂二丁基二月桂酸锡的催化性能明显优于路易斯酸。     

Research progress in synthesis and catalysis of polyoxometalates

Polyoxometalates (POMs) form a large class ofmetal oxide cluster type compounds. Their wealthytopology, physical and chemical properties have at tracted increasing interests. In this paper, based onour group’s research, we review the latest progress inthe synthetic chemistry and catalysis of POMs and in troduce some POMs with novel structure and theirderivatives that emerged in 2002—2004. Most of thecited references come from those published in 2003.Due to POMs’superio…     

Natural products as inspiration for the development of asymmetric catalysis

Biologically active natural products often contain particularly challenging structural features and functionalities in terms of synthesis. Perhaps the greatest difficulties are those caused by issues of stereochemistry. A useful strategy for synthesizing such molecules is to devise methods of bond formation that provide opportunities for using enantioselective catalysis. In using this tactic, the desire for a particular target structure ultimately drives the development of catalytic methods. New enantioselective catalytic methods contribute to a greater fundamental understanding of how bonds can be constructed and lead to valuable synthetic technologies that are useful for a variety of applications.     

天然二萜生物碱它拉乌头胺的结构改造

运用氧化剂ＫＭｎＯ４对天然产物ｔａｌａｔｉｓａｍｉｎｅ（它拉乌头胺）进行结构改造，得到３个新的内酰胺型、亚胺型非天然产物     

Structure modification of unsaturated natural products:The epoxidation of carbon-carbon double bonds in some natural products with hydrogen peroxide catalyzed by iodine

Aim To afford an environmentally benign catalytic epoxidation of carbon-carbon double bonds in organic substrates using hydrogen peroxide as an oxidant and iodine as a catalyst.Method The effects of di...     

电解致酸脱保护DNA在片合成研究

提出了以电解致酸脱保护法为特征的是阻DNA在片合成新方法，在2．0V电解电位下电解水，释放氢离子并富集于阳极极板队近，导致局部酸度增强，使核酸单体分子发生脱保护反应，测定了该合成方法的合成产率与电解时间，支持电解质浓度，水浓度等条件的关系，结果表明，电解时间越长，脱保护效率越高，两者基本呈线性关系；支持电解质浓度与水浓度等条件对脱保护效率基本无影响。     

液—液相转移催化法合成5—邻氯苯基—2—呋喃甲酰芳胺

在液－液相转移催化条件下，合成了１７个５－邻氯苯基－２－呋喃甲酰芳胺，通过红外光谱和元素分析确定了其结构     

气固相催化合成2,6-二甲基哌嗪宏观动力学研究

目的在确定了气固相合成2,6-二甲基哌嗪的最佳工艺条件下对催化合成2,6-二甲基哌嗪的宏观动力学进行研究。方法实验采用改性后的γ-Al2O32mm×2mm柱状催化剂,以工业品1,2-丙二胺为原料,选用平推流反应器,气固相催化法合成2,6-二甲基哌嗪。结果在300～340℃下,建立了合成2,6-二甲基哌嗪的宏观动力学模型。结论此模型的建立可以指导中试放大和工业化生产。     

合成乙二醇单烷基醚乙酸酯的催化剂研究

详细介绍了评述了阳离子交换树脂、分子筛负载TiO2/SO42-、稀土盐、层柱状粘土等不同催化剂催化合成乙二醇单烷基醚乙酸酯的方法。探讨了用硫酸氢钠催化合成乙二醇单甲醚乙酸酯的最佳条件。结果表明，硫酸氢钠是催化合成乙二醇单甲醚乙酸酯的良好催化剂，用量少、收率高、操作简便。