手性药物催化β-酮酸酯不对称α-羟基化反应研究

以商业化易得的具有碱性氮原子的手性药物为有机催化剂,用于催化β-酮酸酯不对称α-羟基化反应,发现以噻吗洛尔或普萘洛尔为催化剂,反应对映选择性分别可达32%和18%.对噻吗洛尔和普萘洛尔进行结构修饰,合成了12个洛尔药物类似物,并考察了其催化效果,发现在优化的反应条件下,以30mol%(R)-1-叔丁胺基-3-(2-萘氧基)-2-丙醇(7f)为催化剂,20mol%β-环糊精为助催化剂,叔丁基过氧化氢为氧化剂,正己烷为溶剂,反应对映选择性最高可达57%,收率92%.不对称α-羟基化产物(S)-5-氯-2-羟基-1-茚酮-2-甲酸甲酯(2a)在乙酸乙酯中一次重结晶后,对映体光学纯度可达99%,收率68%.     

负载型铁基复合氧化物催化苯酚羟基化的研究

在温和条件下对铁基复合氧化物催化苯酚和过氧化氢的羟基化反应进行了研究.结果表明,活性组分、载体以及催化剂/苯酚(质量比)、过氧化氢/苯酚(摩尔比)、反应温度和反应时间等对苯酚羟基化反应具有重要影响.Fe-A催化剂的活性组分形成了α-Fe2O3和尖晶石结构;Fe-B催化剂活性组分以非晶态分布在催化剂上,高度弥散,具有更好的催化性能.溶剂的加入,有助于苯酚和过氧化氢的混合,水是理想的羟基化反应溶剂,可以实现苯酚和过氧化氢水溶液的互溶,有利于·OH的生成.以Fe-B作催化剂,水为溶剂,反应温度65℃,反应时间1h,催化剂/苯酚(质量比)=0.02,水/苯酚(体积比)=2.0,过氧化氢/苯酚(摩尔比)=0.3,苯酚转化率21.6%,苯二酚选择性86.5%.     

脂肪酶催化缩聚法合成可完全降解的聚羟基丙酸酯(英文)

以3-羟基丙酸甲酯为聚合单体,建立了以固定化脂肪酶Novozym 435为催化剂的酶催化缩聚反应体系,合成可完全降解的高分子聚酯聚羟基丙酸酯,考察了反应条件和介质对反应性能的影响,结果表明,纯度大于95%的单体即可在温和条件下合成聚羟基羧酸酯;降低反应压力可有效提升产物产率和分子量.通过选择合适的有机溶剂介质和表面活性剂,可使产物分子量提升至13000(Mw)以上.脂肪酶催化剂重复利用能力优异,经6批次反应后,其相对活性保持在95%以上.     

羟基磷灰石负载锰催化溴苯的Suzuki反应

以羟基磷灰石(HAP)负载Mn作为催化剂(MnHAP)催化溴苯与苯硼酸的Suzuki交叉偶联反应.以氟离子交换羟基磷灰石的羟基(MnFAP)后,催化剂的活性显著提高,在优化的反应条件下能得到约70%的产率.进一步考察了溶剂和不同取代基的影响.结果表明,MnFAP作用下溶剂极性对反应有很大影响,当溶剂DMF/H2O比例为1/3时产率最高.对于不同取代基取代的溴代芳烃或苯硼酸,可以得到中等产率(18%~46%)的偶联产物.     

改性L石催化苯酚羟基化反应的应用

以L沸石为载体,分别采用浸渍法和离子交换法制备了Cu/L催化剂,并应用于苯酚羟基化反应.在苯酚与双氧水摩尔比等于3的条件下详细考察了反应时间、反应温度、L沸石酸碱性以及Cu的负载量和负载方法等因素对反应的影响.结果表明:采用浸渍法制备的催化剂比离子交换法制备的催化剂具有更高的活性,而且增加催化剂酸量或者升高反应温度均有利于提高苯酚转化.在最佳反应条件下,反应2h苯酚转化率为24.0%,苯二酚选择性为71.4%,其中n(邻苯二酚)/n(对苯二酚)为1.22.     

辛可宁季铵盐的合成及催化不对称烷基化研究

探索了辛可宁季铵盐的通用合成方法, 确定辛可宁与取代苄溴在四氢呋喃中回流为最优反应途径, 合成了11个羟基保留的辛可宁季铵盐, 收率57%~88%, 并合成了4种羟基保护季铵盐, 羟基成醚过程在生成季铵盐前后均可进行, 总收率62%~71%; 羟基酯化只能在生成季铵盐之后进行, 总收率78%. 本文共合成了15个季铵盐(Cn-1~Cn-15), 其中5个为新化合物, 另有4个的合成方法未见文献报道. 选用该类季铵盐催化剂催化二苯亚甲基甘氨酸叔丁酯的不对称苄基化反应, 结果发现, 催化剂苄基具有4-Br取代或羟基成醚均有助于提高反应产物的对映选择性. Cn-9可得到最优的反应结果, 产率93%, e.e.值91%.     

乙酸存在下磷酸铁催化对甲酚气相选择性氧化

 在乙酸存在和空气气氛下,以磷酸铁为催化剂进行了对甲酚气相选择氧化生成对羟基苯甲醛和对羟基苯甲醇的反应. 考察了不同乙酸/对甲酚比和反应温度对反应产物分布的影响. 结果表明,加入乙酸可抑制目标产物深度氧化,促进气相反应中高选择性地生成对羟基苯甲醛和对羟基苯甲醇. 在反应温度为250 ℃,乙酸/对甲酚比为0.9,催化剂用量为0.35 g和对甲酚流速为1.92 g/h时,生成对羟基苯甲醛的选择性为34.4%,生成对羟基苯甲醇的选择性为65.6%.     

无碱条件下Au/ZnO选择性催化氧化1,3-丙二醇合成3-羟基丙酸甲酯

采用溶胶-沉积法合成了高选择性的Au/ZnO催化剂,用于1,3-丙二醇选择性氧化酯化为3-羟基丙酸甲酯的反应.研究了保护剂PVA用量、金溶胶合成温度、金负载量及催化剂循环利用对反应的影响,且优化了反应温度和反应压力,并对催化剂进行了XRD和TEM表征.结果表明,PVA∶Au(m/m)=1∶4、金溶胶合成温度25℃、金负载量1%的Au/ZnO对目标反应的催化活性最好,在100℃和Po2=2MPa的条件下1,3-丙二醇的转化率达82.8%,产物3-羟基丙酸甲酯的选择性达95.4%.Au纳米粒子的粒径影响催化性能,在Au平均粒径为2.8~6.1nm的范围内,产物选择性随Au纳米粒子的粒径的减小而增大,平均粒径在2.8~4.8nm的范围内时,催化剂具有较好的产物选择性(大于90%);Au/ZnO催化剂循环利用4次后催化性能(转化率和选择性)无明显下降;并推测了无碱条件下Au/ZnO选择性催化氧化1,3-丙二醇合成3-羟基丙酸甲酯的反应机制.     

微波辅助合成邻羟基苯丁酮

利用微波辅助,以丁酸苯酯为原料,经Fries重排制备了邻羟基苯丁酮.通过单因素实验考察了反应时间、催化剂用量及反应温度对收率的影响,正交实验确定了最优工艺条件.结果表明,当n(催化剂):n(丁酸苯酯)=1.6,反应温度120℃,反应时间8 min时,丁酸苯酯完全转化,邻羟基苯丁酮收率45.0%.     

Rh-CeO2催化剂表面CO还原NO反应中羟基介导NH3生成问题的探讨

CO催化还原NO是发生在汽车尾气净化催化剂中的一个重要化学反应.CeO2容易发生氧化还原反应CeO2?CeO2?x+(x/2)O2而具有氧储存/释放作用,可以有效地促进CO氧化,因而CeO2作为储氧材料和催化助剂被广泛应用于汽车催化剂中.在过渡金属元素中,铑对NO的解离活性最高,是目前汽车三效催化剂中最为重要的还原性活性组分.目前,有关Rh-CeO2基催化剂表面CO还原NO的文献仅关注催化反应活性和N2O选择性,对CO还原NO反应机理的理解还不够深入准确,无法为轻型汽油车NH3排放控制提供正确有用的理论基础.NH3排放至大气中会以NH4+形式与SO42?和NO3?离子结合,导致二次颗粒物污染,因此,研究CO还原NO反应中NH3生成机理对轻型汽油车NH3排放控制具有非常重要的理论意义.我们研究组强调了CO催化还原NO反应的表面羟基介导NH3生成问题,并通过原位漫反射傅里叶变换红外光谱(in-situ DRIFTS),傅里叶变换红外光谱(FT-IR),程序升温还原/氧化(TPR/TPO)等现代分析表征技术深入研究了CO还原NO反应机理,并首次提出了催化剂表面"羟基脱氢"反应的NH3生成机理.研究发现,Rh-CeO2催化剂表面CO还原NO反应的NH3选择性最高可达9.7%,其反应表观活化能仅为36 kJ/mol,in-situ DRIFTS,FT-IR和NO-TPO测试结果表明,NH3的生成可归因于催化剂表面"羟基脱氢"反应,即CO与催化剂表面端位羟基和桥式羟基发生"水煤气转化"反应生成H2,反应产生的H2还原NO生成NH3;CeO2中非骨架铈双羟基化形成的类氢氧化铈物种则会直接与NO发生脱氢反应生成NH3,但需要更高的反应温度.值得注意的是,当反应气中额外通入5%水蒸气时,其反应表观活化能提高了21 kJ/mol(同比增加58.3%),更重要的是NH3选择性明显提高,最高可达25.3%(同比增加160.8%),FT-IR测试结果表明,这是由于水蒸气作用促使催化剂表面羟基化,表面活性氢源得以不断补充.这从动力学角度促进了端位羟基和桥式羟基的"水煤气转化"反应而提高NH3选择性.同时,对比NO/H2,CO/NO和CO/NO/H2O反应的NH3生成浓度,我们还发现,H2O分子与NO的竞争吸附会抑制未解离吸附的NH3进一步还原NO,减少反应生成NH3的消耗,促使更多生成的NH3从催化剂表面脱附至气相中,这也是水蒸气导致NH3选择性明显增加的重要原因.以上结果清晰地表明了催化剂表面"羟基脱氢"作用和水蒸气分子与NO的竞争吸附行为对CO还原NO反应中NH3生成的重要影响.     

Enantioselective indole Friedel--Crafts alkylations catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes

A highly enantioselective Friedel-Crafts alkylation of electron-rich aromatic nucleophiles catalyzed by scandium(III) triflate-pyridyl(bis)oxazoline complexes has been accomplished. The reaction involves alpha,beta-unsaturated acyl phosphonates as electrophiles and primarily substituted indoles as nucleophiles. The reactive acyl phosphonate product is converted to the corresponding ester or amide in good overall yield by adding an alcohol or amine directly to the reaction mixture.     

Trapping of the putative cationic intermediate in the Morin rearrangement with carbon nucleophiles.

This paper presents reactions in which the putative cationic intermediate in the Morin rearrangement is trapped by aromatic carbon nucleophiles (indoles and furans). For example, reaction of sulfoxide 27 with trifluoroacetic acid in chloroform provides, among other products, indole 29 and indoline 30. The indoline was shown to be in equilibrium with the nine-membered ring bridged indole 31. Other examples of Morin rearrangement-trapping reactions are presented, and mechanisms for these transformations are proposed.     

有机催化靛红衍生酮亚胺与噁唑酮的不对称Mannich型加成反应

研究了手性磷酸催化的靛红衍生酮亚胺与噁唑酮的不对称Mannich型加成反应, 以良好至优秀的收率(高达97%)、 对映选择性(高达99% e.e.)以及非对映选择性(均>20∶1 d.r.)得到一系列含噁唑酮骨架的手性3,3′-二取代氧化吲哚化合物. 该反应可以进行扩大化和衍生反应.     

Rhodium‐Catalyzed CH Annulation of Nitrones with Alkynes: A Regiospecific Route to Unsymmetrical 2,3‐Diaryl‐Substituted Indoles

The direct C? H annulation of anilines or related compounds with internal alkynes provides straightforward access to 2,3‐disubstituted indole products. However, this transformation proceeds with poor regioselectivity in the synthesis of unsymmetrically 2,3‐diaryl substituted indoles. Herein, we report the rhodium(III)‐catalyzed C? H annulation of nitrones with symmetrical diaryl alkynes as an alternative method to prepare 2,3‐diaryl‐substituted N‐unprotected indoles with two different aryl groups. One of the aryl substituents is derived from N?C‐aryl ring of the nitrone and the other from the alkyne substrate, thus providing the indole products with exclusive regioselectivity.     

Rhodium‐Catalyzed C?H Annulation of Nitrones with Alkynes: A Regiospecific Route to Unsymmetrical 2,3‐Diaryl‐Substituted Indoles

The direct C H annulation of anilines or related compounds with internal alkynes provides straightforward access to 2,3‐disubstituted indole products. However, this transformation proceeds with poor regioselectivity in the synthesis of unsymmetrically 2,3‐diaryl substituted indoles. Herein, we report the rhodium(III)‐catalyzed C H annulation of nitrones with symmetrical diaryl alkynes as an alternative method to prepare 2,3‐diaryl‐substituted N‐unprotected indoles with two different aryl groups. One of the aryl substituents is derived from NC‐aryl ring of the nitrone and the other from the alkyne substrate, thus providing the indole products with exclusive regioselectivity.     

Asymmetric Dearomatization of Indole Derivatives with N‐Hydroxycarbamates Enabled by Photoredox Catalysis

Dearomatization of indoles provides efficient synthetic routes for substituted indolines. In most cases, indoles serve as nucleophiles. Reported here is an asymmetric dearomatization reaction of indole derivatives that function as electrophiles. The combination of a photocatalyst and chiral phosphoric acid open to air unlocks the umpolung reactivity of indoles, enabling their dearomatization with N‐hydroxycarbamates as nucleophiles. A variety of fused indolines bearing intriguing oxy‐amines were constructed in excellent yields with moderate to high enantioselectivities. Mechanistic studies show that the realization of two sequential single‐electron transfer oxidations of the indole derivatives is key, generating the configurationally biased carbocation species while providing the source of stereochemical induction. These results not only provide an efficient synthesis of enantioenriched indoline derivatives, but also offer a novel strategy for further designing asymmetric dearomatization reactions.     

Catalytic Asymmetric Reactions of 4‐Substituted Indoles with Nitroethene: A Direct Entry to Ergot Alkaloid Structures

A domino Friedel–Crafts/nitro‐Michael reaction between 4‐substituted indoles and nitroethene is presented. The reaction is catalyzed by BINOL‐derived phosphoric acid catalysts, and delivers the corresponding 3,4‐ring‐fused indoles with very good results in terms of yields and diastereo‐ and enantioselectivities. The tricyclic benzo[cd]indole products bear a nitro group at the right position to serve as precursors of ergot alkaloids, as demonstrated by the formal synthesis of 6,7‐secoagroclavine from one of the adducts. DFT calculations suggest that the outcome of the reaction stems from the preferential evolution of a key nitronic acid intermediate through a nucleophilic addition pathway, rather than to the expected “quenching” through protonation.     

Catalytic enantioselective Friedel-Crafts/Michael addition reactions of indoles to ethenetricarboxylates

[reaction: see text] The Friedel-Crafts reaction is an important reaction for the formation of new C-C bonds. Recently, catalytic enantioselective Friedel-Crafts reaction of alkylidene malonates has been reported. However, the substituents in alkylidene malonates are limited. To explore new substituents such as carboxyl and carbonyl groups, catalytic enantioselective Friedel-Crafts reactions of reactive ethenetricarboxylates and acyl-substituted methylenemalonates 1 were investigated. The reaction of 1 with indoles in the presence of catalytic amounts of chiral bisoxazoline copper(II) complex (10%) in THF at room temperature gave alkylated products in high yields and up to 95% ee. The enantioselectivity can be explained by the secondary orbital interaction on approach of indole to the less hindered side of the 1-Cu(II)-ligand complex.     

Gold(I)‐Catalyzed Rearrangement of 3‐Silyloxy‐1,5‐enynes: An Efficient Synthesis of Benzo[b]thiophenes,Dibenzothiophenes, Dibenzofurans,and Indole Derivatives

With the IPr ligand (IPr=1,3‐bis‐(2,6‐diisopropylphenyl)imidazol‐2‐ylidene) on gold(I) excellent yields in the benzanellation of 2‐substituted thiophenes, benzothiophenes, pyrroles, benzofurans, and indoles were achieved. The 1‐siloxybut‐3‐ynyl side chains, incorporated in the anellation, are easily accessible by the addition of a propargyl metal reagent to a formyl group and silylation of the alcohol. This conveniently allows an anellation at the position of the formyl group under mild conditions. All reactions involve a 2,3‐shift of the side chain in the anellation step and thus, provide an easy access to specific substitution patterns. Only in the case of 2‐substituted indoles with their highly nucleophilic 3‐position a direct hydroarylation without shift is observed. On the other hand, 3‐substituted indoles give the same products as 2‐substituted indoles. Then, a 3,2‐shift in the indole ring system has to be involved.     

Platinum‐Catalyzed Multi‐Step Reaction of Propargyl Alcohols with N‐Heteroaromatics

N‐Methyl indole reacts with but‐2‐yn‐1‐ol in the presence of PtCl₂ in MeOH giving indole derivatives having a substituted 3‐oxobutyl group at the 3‐position in good yield. Under the reaction conditions, various substituted indoles and substituted propargyl alcohols are successfully involved in the reaction giving the corresponding addition products in good to moderate yields. The catalytic reaction can be further extended to N‐phenyl pyrrole. In the present multi‐step reaction, PtCl₂ likely plays dual roles: as the catalyst for the rearrangement of propargyl alcohols to the corresponding alkenyl ketones and as the catalyst for the addition of indoles to the alkenyl ketones. Experimental evidence is provided to support the proposed mechanism.