α-氰醇立体选择性合成新进展

总结了近十年来立体选择性合成α-氰醇的最新进展, 包括金属配合物催化的醛、酮类底物的立体选择性氢氰化和硅氰化反应, 不含金属的有机小分子催化剂催化的醛、酮类底物的立体选择性硅氰化反应以及生物催化的立体选择性氢氰化反应. 另外对部分反应中涉及的机理也作了介绍.     

有效控制活性酵母细胞催化β-羰基酯不对称还原反应立体选择性的研究

 以4-氯乙酰乙酸乙酯为β-羰基酯的模型底物,对面包酵母催化其不对称还原反应立体选择性的控制进行了研究. 实验发现,利用诸如烯丙基醇和烯丙基溴等酶抑制剂对面包酵母进行预处理,可以控制反应的立体选择性. 用烯丙基醇预处理面包酵母时可以提高S型产物的立体选择性; 用烯丙基溴预处理时,可以使反应的立体选择性从通常的S型产物转变为R型产物. 立体选择性随着预处理时抑制剂浓度的增大和处理时间的延长而提高. 合适的预处理条件可使S型和R型产物的ee值分别达到95%和98%.     

立体选择性烯烃复分解反应的研究及应用

烯烃复分解反应是基于钌卡宾催化的形成碳碳双键的重要反应之一,近年来关于立体选择性烯烃复分解反应的研究越来越多.综述了近年来基于钌催化的立体选择性烯烃复分解反应,包括金属钌催化剂的种类、演化、立体选择性研究进展及其在不对称合成中的应用.重点介绍了近十年来钌催化烯烃复分解反应类型及其在不对称合成中的应用研究进展,并对今后的发展做出展望.     

手性催化的环氧化物立体选择性开环反应

手性催化的环氧化物立体选择性开环反应可以用来制备多种具光学活性的化合物, 因而成为有机合成中极为重要的方法之一. 多种亲核试剂都已成功应用于此类反应. 综述了近十年来环氧化物的立体选择性开环反应方面的一些最新研究进展.     

微波促进立体选择性高效合成糖基α,β-不饱和酯类化合物

利用微波促进糖醛与叶立德(Ph3P=CHCOOEt)发生Wittig反应,立体选择性地合成了含有α,β-不饱和酯的糖烯类化合物,反应效率显著提高,使用不同的反应溶剂可实现对反应立体选择性的控制.并通过1H NMR中双键氢的偶合常数确定了产物的构型.     

Cu(Ⅱ),Zn(Ⅱ)-手性二噁唑啉配合物催化硝酮与烯烃环加成反应立体选择性的理论研究

用理论计算方法研究了Cu(Ⅱ)和Zn(Ⅱ)-手性二恶唑啉络合物与N-苄基-α-乙氧酰基硝酮形成的反应前驱体与乙基乙烯基醚的1,3-偶极环加成反应过程.讨论了反应前驱体的前线轨道和优化的分子结构对环加成反应的速度和立体选择性的影响,对手性金属催化剂存在下的1,3-偶极环加成反应的立体选择性进行合理解释.还讨论了催化反应和非催化反应速度对反应立体选择性的影响.     

己二烯基烯丙基醚的Wittigσ迁移重排反应

烯丙基醚类的[2.3]Wittig σ迁移重排反应是近几年来新发展的一个有机合成反应。由于此反应具有高度的非对映选择性和立体选择性,它为合成中的碳链延伸、立体选择性反应及不对称合成提供了一个新的方法,因为此反应可通过选择底物的几何构型和取代基得到立体选择性产物。[2.3]Wittig σ迁移重排     

烯烃亲电加成反应的教学研究

烯烃的典型反应是亲电加成反应.大学有机化学教学目标要求学生掌握并能熟练应用烯烃亲电加成反应的区域选择性、立体选择性以及烯烃的反应活性解决实际问题.具体包括:(1)使用区域选择性预测加成主副产物;(2)使用立体选择性判断加成产物立体结构;(3)综合考虑电子效应,熟练比较各种烯烃的反应活性.由于烯烃亲电加成反应底物多、影响...     

Diels-Alder反应中的次级轨道效应

利用概念密度泛函理论下的局域软度和广义局域软度,结合局域硬软酸碱(HSAB)原理,研究环戊二烯与CH2=CHCOCnH2n+1之间的Diels-Alder反应的立体选择性,其中活性因子均是由ABEEMσπ模型获得.与以往不同的是,除了将主要参与反应的4个原子作为反应中心之外,还将产生次级轨道效应(SOI)的2个原子也作为参与反应的一部分.得到的结果表明,所有反应的立体选择性均与实验结果取得了很好的一致性,由此提出了一种定量快速处理包含次级轨道效应的Diels-Alder反应的立体选择性的方法.     

高立体选择性地合成薄荷基溴和新薄荷基溴

薄荷基溴和新薄荷基溴是一类非常有用的不对称合成中间体。以L-薄荷醇为原料,通过与不同的溴化剂反应高立体选择性地得到薄荷基溴和和新薄荷基溴。当L-薄荷醇与盐酸和无水溴化锌反应时高立体选择性地得到薄荷基溴,当L-薄荷醇与三溴化磷反应时高立体选择性地得到新薄荷基溴.     

Do reaction conditions affect the stereoselectivity in the Staudinger reaction?

The stereochemistry is one of the critical issues in the Staudinger reaction. We have proposed the origin of the stereoselectivity recently. The effects of solvents, additives, and pathways of ketene generation on the stereoselectivity were investigated by using a clean Staudinger reaction, which is a sensitive reaction system to the stereoselectivity. The results indicate that the additives, usually existed and generated in the Staudinger reaction, and the pathways of the ketene generation do not generally affect the stereoselectivity. The solvent affects the stereoselectivity. The polar solvent is favorable to the formation of trans-beta-lactams. The addition orders of the reagents affect the stereoselectivity in the Staudinger reaction between acyl chlorides and imines. The addition of a tertiary amine into a solution of the acyl chloride and the imine generally decreases the stereoselectivity, which is affected by the interval between additions of the acyl chloride and the tertiary amine, and the imine substituents. Our current results provide further understanding on the stereochemistry of the Staudinger reaction between acyl chlorides and imines and on the factors affecting the stereochemistry and also provide a method to prepare beta-lactams with the desired relative configuration via rationally tuning the stereoselectivity-controlling factors in the Staudinger reaction.     

Stereocontrolled synthesis of linear 22R-homoallylic sterols via a triflic acid-catalyzed 2-oxonia Cope rearrangement

[reaction: see text] Poor stereoselectivity caused by the involvement of side reaction pathways was observed in the In(OTf)(3)-catalyzed allyl-transfer reaction (R = electron-withdrawing group). Subsequently, it was found that the employment of triflic acid (TFA) as catalyst could successfully suppress the side reaction pathways and, hence, achieve high stereoselectivity.     

Catalytic effect of nanosized metal oxides in the Biginelli reaction

The effect of nanosized metal oxides on the regio- and stereoselectivity of the multicomponent Biginelli reaction and the reaction mechanism under conditions of heterogeneous catalysis were studied. It was found that the considerable activation of reagents occurred on the surface of metal nanooxides. The Biginelli reaction occurred by two mechanisms: a carbocationic mechanism took place along with the generally accepted mechanism (through the N-acyliminium ion). Nanosized metal oxides in the presence of chiral inductors increased the regio- and stereoselectivity of the Biginelli reaction.     

Highly enantio- and diastereoselective synthesis of β-methyl-γ-monofluoromethyl-substituted alcohols

Enanatiopure β-methyl-γ-monofluoromethyl alcohols were prepared from the allylic alkylation between fluorobis(phenylsulfonyl)methane with Morita-Baylis-Hillman carbonates. The reaction was catalyzed by using the Cinchona alkaloid derivative, (DHQD)(2)AQN. The origin of the stereoselectivity was verified by DFT methods. Calculated geometries and relative energies of various transition states strongly support the observed stereoselectivity.     

Studies of a proposed mechanism for the reaction between 2H-pyran-2-ones and organomagnesium compounds

Part of the reaction between 2H-pyran-2-ones and organomagnesium compounds has been investigated by means of MNDO and ab initio calculations. Criteria for the mechanism of reaction are provided by the stereoselectivity observed and calculations are consistent with this stereoselectivity. Conformations of the reaction intermediates are given.     

Dipole interaction-controlled stereoselectivity in aldol reaction of alpha-CF3 enolate with fluoral

The stereoselectivity of a reaction is generally determined by minimizing steric repulsion. However, the aldol reaction of alpha-CF(3)-ketone (Z)-enolate with fluoral anomalously gave an anti-aldol through a sterically demanding transition state, because of the strong dipole interaction of the two CF(3) groups. We have thus disclosed a paradigm shift from steric to electronic control of reaction stereoselectivity. [reaction: see text]     

Studies on the factors that affect stereoselective esterification of (R,S) 2-octanol with octanoic acid catalyzed by lipase in organic solvent

Stereoselective esterification of(R, S) 2-octanol with octanoic acid catalyzed byCandida Sp lipase (CSL) was carried out in cyclohexane. We have studied the effects of factors, such as temperature and the microenvironment of lipase, on this reaction. The results showed that CSL favoredR enantiomer of(R, S) 2-octanol, and that the esterification activity and stereoselectivity of the lipase were dependent on these factors. The higher the temperature, the greater the esterification activity of CSL. A slight increase in stereoselectivity can be seen with temperature decrease. The optimal range of pH value for this reaction was 4.9–6.2. When the salt concentration was between 0 and 0.05 mol/L, CSL showed high activity. The salt concentration in the reaction system and the pH value at which CSL powder was prepared from the aqueous solution had no evident effect on the stereoselectivity of CSL. The optimal range of the water content in the reaction system was 0.4–1.6%. The esterification activity and the stereoselectivity of CSL were enhanced 1.4-fold and 2.0-fold, respectively, by immediately removing the produced water. (S) 2-octanol with 95.2% enantiomeric excess (ee) was prepared. Based on these results, we have discussed why that all these factors affected this reaction.     

Reactivity of 2-Methylene-1,3-dicarbonyl Compounds. Stereoselective and Asymmetric Diels-Alder Reactions

The Diels-Alder reaction of 1,1-dicarbonylethenes 1 with dienes was investigated. The adduct of the reaction of 1, whose two carbonyl groups were different, with cyclopentadiene showed moderate stereoselectivity and this was explained by FMO theory. However, in the Lewis acid-catalyzed addition, the reaction proceeded with high stereoselectivity to give the exo adduct 3x. This might be due to steric hindrance because the benzene ring cannot orient in the plane of the conjugated system in the metal-chelated enedione 6. Applying this principle to (1'R,2'S,5'R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl 2-benzoylacrylate (1d), we achieved a diastereomeric Diels-Alder reaction to afford 3x-R, whose structure was confirmed by the X-ray crystal analysis.     

Stereoselectivity of the cyclooctene ring-opening polymerization

The stereoselectivity of the cyclooctene ring-opening polymerization in the presence of the tungsten hexachloride–tetraisobutylalumoxane (TBAO) catalyst system has been studied. The reaction conditions have been established in which the polymer chain isomerization is reduced to a minimum. Under these conditions the stereoselectivity is determined by an individual act of the monomer molecule insertion. The dependence of stereoselectivity on monomer concentration, number of active sites, and temperature has been investigated. The results obtained suggest that the cyclooctene polymerization is selective in favor of the geometrical configuration of the starting cycloolefin (the “retention” effect) by analogy with the previously reported metathesis of acyclic olefins. Considerations which support the idea that cis and trans units are reproduced by the same type of active sites are discussed. The experimental evidence indicates that in this case the stereoselectivity is determined by the difference in kinetics of two reaction paths of the monomer molecule insertion that lead to the formation of cis and trans units.     

Origin of the relative stereoselectivity of the beta-lactam formation in the Staudinger reaction

The relative (cis, trans) stereoselectivity of the beta-lactam formation is one of the critical issues in the Staudinger reaction. Although many attempts have been made to explain and to predict the stereochemical outcomes, the origin of the stereoselectivity remains obscure. We are proposing a model that explains the relative stereoselectivity based on a kinetic analysis of the cis/trans ratios of reaction products. The results were derived from detailed Hammett analyses. Cyclic imines were employed to investigate the electronic effect of the ketene substituents, and it was found that the stereoselectivity could not be simply attributed to the torquoelectronic model. Based on our results, the origin of the relative stereoselectivity can be described as follows: (1) the stereoselectivity is generated as a result of the competition between the direct ring closure and the isomerization of the imine moiety in the zwitterionic intermediate; (2) the ring closure step is most likely an intramolecular nucleophilic addition of the enolate to the imine moiety, which is obviously affected by the electronic effect of the ketene and imine substituents; (3) electron-donating ketene substituents and electron-withdrawing imine substituents accelerate the direct ring closure, leading to a preference for cis-beta-lactam formation, while electron-withdrawing ketene substituents and electron-donating imine substituents slow the direct ring closure, leading to a preference for trans-beta-lactam formation; and (4) the electronic effect of the substituents on the isomerization is a minor factor in influencing the stereoselectivity.