手性磺酰胺有机小分子催化剂在不对称催化反应中的应用进展

有机小分子催化的不对称合成反应是目前研究最为活跃的领域之一.综述了磺酰胺类衍生物作为小分子催化剂在不对称反应(Michael加成反应、Mannich反应、羟醛缩合反应等)中的应用,讨论了磺酰胺中NH的酸性以及氢键性质在不对称催化反应中的的作用.     

A Simple Model for Barrier Frequencies for Enzymatic Reactions

We present a simple model to rationalize the effects of environment on the reaction barrier frequencies derived from free energy profiles. These frequencies are relevant in deviations of a rate constant from its transition state theory value and in determining which environmental dynamics participate in the reaction. In particular, this simple model can be used to understand the changes in the reaction barrier frequencies of an enzymatic catalyzed reaction and the corresponding uncatalyzed process in aqueous solution, a change which has implications for dynamical environmental effects on the enzymatic reaction. Two possible cases are analyzed, in which the polarity (charge separation/localization) of the reacting system increases or decreases as the reaction advances. A simple modeling of the environment′s effects allows the explanation of an unusual “inverse” effect on the reaction frequencies, that is, a free energy barrier lowering accompanied by an increase of the reaction frequency, a behavior observed in some enzymes. The model predictions are successfully compared with results from full simulations for four different enzyme reactions.     

Domino reactions that combine an azido-Schmidt ring expansion with the Diels-Alder reaction

[reaction: see text] The combination of the intramolecular Schmidt reaction with the Diels-Alder reaction provides expedient access to a variety of heterocycles. Two different modes of reaction planning are presented. In one, the azide and ketone moieties necessary for the intramolecular Schmidt reaction originate on different molecules that are reacted and subsequently undergo a ring-adjustment step. Alternatively, an azido ketone can be used provided the ketone is deactivated by its presence in an enone.     

Enzymatic Ugi Reaction with Amines and Cyclic Imines

The application of the Ugi reaction to the construction of new peptide scaffolds is an important goal of organic chemistry. To date, there are no examples of the Ugi reaction being performed with a cyclic imine and amine simultaneously. The application of 2‐substituted cyclic imines in an enzymatic three‐component Ugi‐type reaction provides an elegant and attractive synthesis of substituted pyrrolidine and piperidine derivatives in up to 60 % yield. Results on studies of the selection of an enzyme, amount of water, and solvent used in a novel three‐component Ugi reaction and the limitations thereof are reported herein. The presented methodology exploiting enzyme promiscuity in the multicomponent reaction fulfills the requirements associated with green chemistry. Several methods, such as isotope labeling and enzyme inhibition, were used to probe the possible mechanism of this complex synthesis. This research is the first example of an enzyme‐catalyzed Ugi‐type reaction with an imine, amine, and isocyanide.     

Asymmetric Schmidt reaction of hydroxyalkyl azides with ketones

An asymmetric equivalent of the Schmidt reaction permits stereocontrol in ring expansions of symmetrical cyclohexanones. The procedure involves the reaction of chiral 1,2- and 1,3-hydroxyalkyl azides with ketones under acid catalysis; the initial reaction affords an iminium ether that can be subsequently opened with base. A systematic study of this reaction is reported, in which ketone substrates, chiral hydroxyalkyl azides, and reaction conditions are varied. Selectivities as high as ca. 98:2 are possible for the synthesis of substituted caprolactams, with up to 1,7-stereoselection involved in the overall process. The fact that either possible migrating carbon is electronically identical provides an unusual opportunity to study a ring-expansion reaction controlled entirely by stereoelectronic factors. The mechanism of the reaction and the source of its stereoselectivity are also discussed.     

迈克尔反应受体分子化学生物学研究

迈克尔受体是烯键或炔键与吸电子基团共轭相连形成的官能团,含有这样官能团的化学小分子能与亲核试剂发生迈克尔加成反应,因此称为迈克尔反应受体分子。迈克尔反应受体分子是一类重要的生理活性分子,它们直接或间接参与许多生命过程,同时也是细胞中许多信号转导途径的调节者,在化学生物学研究中起着重要的作用。本文对迈克尔反应受体分子化学生物学研究进展进行了综述。     

The Paternò-Büchi reaction—Mechanisms and application to organic synthesis

The [2 + 2] photocycloaddition between an electronically excited carbonyl compound and an alkene leading to oxetanes (Paternò-Büchi reaction) is one of the most investigated organic photochemical reaction. Regio-, stereo- and site selectivities are discussed as a consequence of the reaction mechanism. Spin multiplicity and electron transfer have a significant impact on the outcome of the reaction. Typical carbonyl and alkene reaction partners are presented indicating scope and limitation of the reaction. The Paternò-Büchi reaction possesses particular interest for being applied to organic synthesis, considering the difficulty for non-photochemical reactions to obtain oxetanes, with or without stereoselectivity. Mechanistic details are particularly focused. It has been applied as key step in various multi-step syntheses.     

连续电荷传递反应的阻抗谱与电极反应机制的关系

对于含有一个吸附中间物的不可逆连续电行传递反应，在较低的过电位下，电极过程的Faraday阻抗通常在复平面上显示一个低频感抗弧．在较高的过电位下，这个感抗弧将转化为容抗弧，这一转变预示着速控步骤的变化．相反，当反应速率一直被其中的一个步骤控制时，它的法拉第弛豫始终表现出容抗行为．     

Selective oxidative cyclization by FeCl3 in the construction of 10H-indeno[1,2-b]triphenylene skeletons in polycyclic aromatic hydrocarbons

A novel family of polycyclic aromatic hydrocarbons of various shapes based on the 10H-indeno[1,2-b]triphenylene skeleton has been synthesized via a reaction sequence of Diels-Alder reaction, decarbonylation, followed by an oxidative cyclization. In particular, the reaction conditions for regioselective oxidative cyclization promoted by FeCl3 are investigated, and this reaction is employed as an effective method to afford the above molecules under mild conditions. Their photophysical properties in dilute solution are also reported.     

关于反应分子数定义的讨论

There are two different views on the definition of reaction molecularity in physical chemistry textbooks and related literatures so far. We give a deep discussion about this conception herein. Starting with the development of chemical kinetics and the definition of elementary reaction and state-state reaction, we clarify that elementary reaction and state-state reaction are the conceptions belonging to macro-and micro-systems, respectively, and reaction molecularity is also belonging to micro-conception. Based on this conclusion, we think that the more reasonable definition of reaction molecularity should be "the number of chemical particles that take part in a state-state reaction (or an elementary chemi-physical reaction) as a reactant".     

Iron‐Catalyzed C?H Bond Activation for the ortho‐Arylation of Aryl Pyridines and Imines with Grignard Reagents

Direct arylation of the ortho‐C? H bond of an aryl pyridine or an aryl imine with an aryl Grignard reagent has been achieved by using an iron‐diamine catalyst and a dichloroalkane as an oxidant in a short reaction time (e.g., 5 min) under mild conditions (0 °C). The use of an aromatic co‐solvent, such as chlorobenzene and benzene, and slow addition of the Grignard reagent are essential for the high efficiency of the reaction. The present arylation reaction has distinct merits over the previously developed reaction that used an arylzinc reagent, such as its reaction rate and atom economy. Selective C? H bond activation occurs in the presence of a leaving group, such as a tosyloxy, chloro, and bromo group. Studies on a stoichiometric reaction and kinetic isotope effects shed light on the reaction intermediate and the C? H bond‐activation step.     

Catalytic asymmetric Henry reaction

The classical Henry reaction, the coupling of a nitroalkane with a carbonyl compound in the presence of a base, is an important C–C bond forming reaction in organic chemistry giving β-nitroalcohols, which are useful synthons in organic synthesis. However, an asymmetric version of the reaction, that has been developed recently, gives a new dimension to the classical Henry reaction whereby the control of stereochemistry of two newly generated carbon centres has become possible. In this review, the various catalytic methods for this purpose are discussed.     

Development of an organo- and enzyme-catalysed one-pot,sequential three-component reaction

A one-pot, three-component process is described which involves both organo- and enzyme-catalysed carbon–carbon bond-forming steps. In the first step, an organocatalyst catalyses the aldol reaction between acetaldehyde and a glyoxylamide. After dilution with additional aqueous buffer, and addition of pyruvate and an aldolase enzyme variant, a second aldol reaction occurs to yield a final product. Crucially, it was possible to develop a reaction in which both the organo- and enzyme-catalysed reactions could be performed in the same aqueous buffer system. The reaction described is the first example of a one-pot, three-component reaction in which the two carbon–carbon bond-forming processes are catalysed using the combination of an organocatalyst and an enzyme.     

Click To Bind: Metal Sensors

The copper‐catalyzed azide–alkyne “click” cycloaddition reaction is an efficient coupling reaction that results in the formation of a triazole ring. The wide range of applicable substrates for this reaction allows the construction of a variety of conjugated systems. The additional function of triazoles as metal‐ion ligands has led to the click reaction being used for the construction of optical sensors for metal ions. The triazoles are integral binding elements, which are formed in an efficient modular synthesis. Herein, we review recent examples of triazoles as a metal‐binding element in conjugated metal‐ion sensors.     

Ethanol Oxidation Reaction Mechanism on Gold Nanowires from Density Functional Theory

Thin gold nanowires (NWs) are materials that could be used as support in different chemical reactions. Using density functional theory (DFT) it was shown that NWs that form linear atomic chains (LACs) are suitable for stimulating chemical reactions. To this end, the oxidation reaction of ethanol supported on the LACs of Au−NWs was investigated. Two types of LACs were used for the study, one pure and the other with an oxygen impurity. The results showed that the oxygen atom in the LAC fulfills important functions throughout the reaction pathway. Before the chemical reaction, it was observed that the LAC with impurity gains structural stability, that is, the oxygen acts as an anchor for the gold atoms in the LAC. In addition, the LAC was shown to be sensitive to disturbances in its vicinity, which modifies its nucleophilic character. During the chemical reaction, the oxidation of ethanol occurs through two different reaction paths and in two stages, both producing acetaldehyde (CH₃CHO). The different reaction pathways are a consequence of the presence of oxygen in the LAC (oxygen conditions the formation of reaction intermediates). In addition, the oxygen in the LAC also modifies the kinetic behavior in both reaction stages. It was observed that, by introducing an oxygen impurity in the LAC, the activation energy barriers decrease ∼69 % and ∼97 % in the first and second reaction stages, respectively.     

Organocatalytic kinetic resolution cascade reactions: new mechanistic and stereochemical manifold in diphenyl prolinol silyl ether catalysis

A new cascade reaction involving an iminium-catalyzed intramolecular oxa-Michael addition followed by an enamine-catalyzed intermolecular Michael addition is reported herein. This cascade reaction generates enantiopure, highly functionalized tetrahydropyrans and tetrahydrofurans in a one-pot reaction and in up to 89?% combined yield and up to 99?% ee. This cascade reaction is catalyzed by diaryl prolinol silyl ethers, which are a privileged class of catalysts. The stereochemical outcome of these cascade reactions is unprecedented. Computational studies indicate that this stereochemical outcome arises from nonclassical hydrogen-bonding interactions between the electrophile and the substrate, and from entropic considerations of preorganization. The unprecedented configurations of the cascade products, combined with the computational models, reveal for the first time that asymmetric induction by diaryl prolinol silyl ether catalysts is not always exclusively reagent controlled. The stereochemical outcome also arises from a kinetic resolution or dynamic kinetic resolution of the β-stereocenter through an enamine-catalyzed intermolecular reaction. This unprecedented organocascade reaction mechanism may be adaptable to diaryl prolinol silyl ether-catalyzed cascade reactions, in which both the iminium- and enamine-catalyzed steps are intermolecular, an underdeveloped type of cascade reaction.     

Synthesis of nitro-substituted decalones by double Michael reaction,sequential Michael reaction,and by Diels-Alder reaction

4-Nitro-3-phenyl-decalones are obtained from 1-acetylcyclohexene by three different ways. Stereochemistry and reaction pathways are discussed, and, for the first time, an intermediate of a sequential Michael reaction is isolated.The Michael reaction is of great preparative value for the formation of CC bonds². We are especially interested in the stereochemistry of the double Michael reaction     

A synthetic approach toward nitiol: construction of two 1,22-dihydroxynitianes

Synthetic work toward the total synthesis of nitiol has culminated in the construction of two epimeric hydroxylated derivatives, the 1,22-dihydroxynitianes. Key stereodefining steps in the construction of the A-ring fragment (13) were the use of a siloxy-epoxide rearrangement reaction, a Pauson-Khand reaction, a Norrish 1 photochemical cleavage reaction, and a highly regio- and stereoselective hydrostannylation reaction of an ynoate. The stereochemistry of the synthetically challenging C-ring fragment (20) was established using an Ireland-Claisen reaction and a Grubbs ring-closing metathesis process as key steps. The 12-membered B-ring of the nitiane skeleton was constructed using a copper-promoted Stille cross-coupling and a Kishi-Hiyama-Nozaki carbonyl addition reaction. Unfortunately, the carbonyl addition reaction produced hydroxyl functionality that could not be selectively removed. Consequently, a synthesis of epimeric 1,22-dihydroxynitianes, which are compounds that are structural hybrids of two natural products, nitiol and variculanol, was completed.     

H＋CH2CO反应机理的G2计算

分别在UQCISD/6-311G(d,p)和G2理论计算水平上，对CH2CO和H反应可能存在的四条反应通道进行了研究，详细分析了每个通道的反应机理;通过振动分析的虚频数和内禀反应坐标(IRC)计算,确认了反应涉及的每一个过渡态.通过反应位能剖面的比较，发现经过一个中间体生成CH3＋CO的一条途径是主反应通道，该通道是个放热反应，总焓变为－146.07 kJ•mol－1，速控步骤的位垒为55.09 kJ•mol－1.理论计算结果较好地解释了实验观察到的主要产物和副产物并存的现象。     

对化学反应数据分类获取反应知识的新方法

尽管已有大量化学反应数据可供使用,但化学家仍常常感到很难便捷地从中得到所需的信息.这主要是由于反应数据库基于结构的检索方法与化学家解决问题的方法相去甚远.为解决这一问题而发展了一种通过对反应进行二级分类得到精细描述反应知识的层次模型的方法.第一次分类时不同的同类反应都在由一组普适性好的称作反应结构一级描述符构成的空间中进行.在第一次分类结果的基础上,得到每一类反应的公共结构特征作为第二次分类的结构描述符,利用它们进行更精细的分类,即可从原始反应数据中得到所需的基核反应.由特定反应、基核反应和基型反应就可将反应知识更合理地组织在同类反应知识库中,使它们得到更好的利用.