系统论述烯烃亲电加成反应的立体选择性

亲电加成是烯烃最具代表性的典型反应,在本科的教学中,要求学生熟练掌握和应用。烯烃的亲电加成反应不仅涉及到反应的活性、区域选择性问题,还涉及到反应的立体选择性问题。但对于立体选择性的阐述,很多教科书并不全面,甚至不够严谨,因而在教学过程中发现学生在理解这部分内容时存在一定的误解。针对这一问题进行了系统的论述,以帮助学生更好更正确地理解和掌握烯烃的亲电加成反应的立体选择性。     

卤化氢与烯烃亲电加成反应的机理及立体选择性*

卤化氢与烯烃的亲电加成反应既是烯烃的重要反应之一,也是一种制备卤代烷的重要方法。现行教材中通常只介绍其分步的碳正离子中间体机理和加成的区域选择性,未涉及反应的立体选择性。介绍了文献中关于该类反应的机理及其立体选择性,希望能够从教学上更新和提高对这类反应的认识。     

含邻手性碳原子双键亲电加成反应的立体选择性模型

本文主要介绍了预测邻位具有手性中心π体系亲电加成反应的立体选择性模型,尤其是α,β-不饱和羰基化合物亲核共轭加成形成的烯醇负离子及其类似物和硝基烯烃亲核加成形成的氮酸根类中间体的烷基化和动力学控制质子化反应的立体选择性模型。立体位阻效应控制的Zimmerman前过渡态模型主要适用于底物构象受限的环状或联烯型烯醇负离子的动力学质子化。对于构象转化相对灵活的直链底物,Houk基于量子化学计算研究提出了亲电试剂的进攻角度或接触角在经过环状过渡态时是锐角还是钝角决定了亲电加成反应的立体选择性控制(Houk模型)。而Fleming模型首次将烯丙基A-1,3张力引入各类烯醇负离子烷基化和质子化的过渡态。Mohrig模型在考虑A-1,3张力的基础上,将吸电子取代基与即将形成的σ键反式共平面,主要阐述了立体电子效应对酯的烯醇负离子动力学控制质子化立体选择性的影响,后来又提出了金属离子参与的立体电子效应控制的六元环状半椅式模型。本文希望对理解亲电加成反应的立体化学控制提供一些有用的信息。     

环氧乙烷亲核开环的区域选择性规则在有机化学教学中的应用

环氧乙烷亲核开环的区域选择性规则是有机化学中典型脂肪三元杂环亲核性开环的选择性规则,具有普遍性。本文以非对称环氧乙烷的亲核性开环为核心,从开环反应过渡态稳定性的角度讨论了决定环氧乙烷亲核开环区域选择性的原因。介绍了该区域选择性规则在经过三元杂环正离子中间体的非对称烯烃亲电加成反应区域选择性教学中的应用。加强学生对不同反应的机理和选择性的联系,起到教学中融会贯通的作用,可以提高教学效率和效果。     

烷氧负离子对偏氟乙烯的亲核加成反应

一般烯烃容易发生亲电加成反应,而全氟或多氟(卤)型烯烃容易发生亲核加成反应。但介于典型烯烃(如乙烯)及典型全氟烯烃(如四氟乙烯)之间的偏氟乙烯是否能进行亲核加成,尚无明确答案。     

Grignard试剂与α-肉桂酰基环二硫缩烯酮的区域选择性加成反 应

乙基、丙基、丁基、苯基和苄基卤化镁等Grignard试剂与具有三个亲电中心的α-肉桂酰基环二硫缩烯酮类化合物2反应,加成反应发生在2中与芳基相邻的碳原子上,生成共轭加成产物3,反应具区域选择性。     

硝酮1,3-偶极环加成对映选择性配合物催化剂的研究进展

近几年来，1，3-偶极环加成的对映选择性金属配合物催化反应得到了较多研究。人们研制出了一系列控制反应立体选择性的金属配合物催化剂，尤其是对硝酮和链烯烃反应，许多催化剂对Dies-Alder反应和1，3-偶极环加成反应同时具有较高的对映及非对映选择性。     

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.     

烯丙型膦叶立德与卟啉铁卡宾反应: 催化的高效、高选择性的分子间卡宾对烯烃C—H键形式插入反应

叶立德作为带有特殊离去基团的碳负离子(亲核试剂)被广泛应用于有机合成研究. 传统的叶立德参与的反应主要有叶立德同亲电的羰基化合物、亚胺以及烯烃的反应, 分别生成烯烃和环氧化合物、氮杂环丙烷化合物以及环丙烷化合物. 亲电的金属卡宾作为一类重要的亲电试剂, 其同叶立德的反应研究报道则很少. 最近, 中国科学院上海有机化学研究所唐勇等发现, 酯基稳定的卟啉铁卡宾可以高效、高选择性地插入到烯丙型膦叶立德的C—H键中. 机理研究表明, 反应经历环丙烷化-开环重排反应的串联过程. 在此基础上, 高立体选择性地实现了1,1,4-三取代共轭丁二烯衍生物的合成, 反应具有很好普适性. 该发现提供了叶立德与金属卡宾(亲电试剂)反应的一种新模式.     

高立体、区域选择性合成(Z)-1-芳硫基-2-芳硒基烯

氢氧化铯催化下,四氢呋喃作溶剂,室温、氮气保护下,炔基硫醚与硒酚发生亲核加成反应,立体选择性合成一系列(Z)-1-芳硫基-2-芳硒基烯,收率70%～93%.反应机理为氢氧化铯与硒酚反应产生的芳硒化铯,随后对炔硫醚进行亲核加成,形成的烯基负离子水解得到产物.     

DFT study on the mechanism of Pd(OAc)<Subscript>2</Subscript>-catalyzed hydrothiolation of alkenes bearing heteroatoms with benzenethiol

The work reports the theoretical investigation of the mechanism and regioselectivity of the Pd(OAc)₂-catalyzed hydrothiolation of heteroatom-substituted alkenes with benzenethiol leading to Markovnikov-type product. The reaction process includes: (1) activation of the S–H bond for benzenethiol by the catalyst Pd(OAc)₂; (2) migratory insertion of the alkenes bearing heteroatoms into the Pd–S bond; (3) AcOH molecule attacks Pd–C bonds to give the product and release the catalyst. In addition, the computed results shown that Pd(OAc)₂-catalyzed hydrothiolation take place by two possible channels and get anti-Markovnikov-type or Markovnikov-type species. The Markovnikov-type reaction channel is more favored with the energy barriers of 21.9–25.6 versus 28.5–31.2 kcal/mol for the anti-Markovnikov-type pathway. The theoretical results and the experimental observations of Tamai and co-workers are consistent. This reaction would proceed in mild conditions and afford the Markovnikov-type products in high yields and regioselectivity.     

Mechanism of Ligand‐Controlled Regioselectivity‐Switchable Copper‐Catalyzed Alkylboration of Alkenes

Cu‐catalyzed alkylboration of alkenes with bis(pinacolato)diboron ((Bpin)₂) and alkyl halides provides a ligand‐controlled regioselectivity‐switchable method for the construction of complex boron‐containing compounds. Here, we employed DFT methods to elucidate the mechanistic details of this reaction and the origin of the different regioselectivity induced by Xantphos and Cy‐Xantphos. The calculation results reveal that the catalytic cycle mainly proceeds through the migratory insertion of alkenes on Cu‐Bpin complex, the oxidative addition of alkyl halides, and the reductive elimination of a C?C bond. Meanwhile, the rate‐ determining step is the oxidative addition of alkyl halides and the regioselectivity‐determining step is the migratory insertion of alkenes. The bulky cyclohexyl group of Cy‐Xantphos facilitates the approach of the substituents of alkenes to Bpin in the migratory insertion step and thus leads to the Markovnikov products. The less bulky phenyl group on Xantphos prefers keeping the substituents of alkenes away from the Bpin moiety in the migratory insertion step and thus results in anti‐Markovnikov products.     

A regioselective Ru-catalyzed alkene-alkyne coupling

[reaction: see text] The reaction of silylalkynes and terminal alkenes proceeds with complete control of regioselectivity by the silyl substituent to give geometrically defined vinylsilanes. Since terminal alkynes normally give mixtures, protodesilylation of these adducts then constitutes a regioselective addition of terminal alkynes to terminal alkenes.     

Allylstannylation of carbon-carbon and carbon-oxygen unsaturated bonds via a radical chain process

In the presence of a radical initiator, allyltributylstannanes bearing an electron-withdrawing group at the beta-position smoothly reacted with electron-deficient terminal alkenes to give allylstannylated products in good yields. The stannyl group was introduced into the terminal carbon with high regioselectivity. The allylstannylation of homochiral 8-phenylmenthyl acrylate proceeded with moderate to good diastereoselectivity. Terminal and electron-deficient internal alkynes as well efficiently underwent the radical-initiated allylstannylation in an anti addition mode. The reaction of terminal alkynes showed the same regioselectivity as that of terminal alkenes. The present radical reaction was applicable to allylation of aromatic aldehydes and ketones.     

Copper‐Catalyzed Carbotrifluoromethylation of Unactivated Alkenes Driven by Trifluoromethylation of Alkyl Radicals

We report herein an unprecedented protocol for radical carbotrifluoromethylation of unactivated alkenes. With Cu(OTf)₂ as the catalyst, the reaction of unactivated alkenes, TMSCF₃ and activated alkyl chlorides at room temperature provides the corresponding carbotrifluoromethylation products in satisfactory yields. Directed by trifluoromethylation of alkyl radicals, the method exhibits an excellent regioselectivity that is opposite to those driven by CF₃ radical addition.     

Studies on The Application of The Paternò-Büchi Reaction to The Synthesis of Novel Fluorinated Scaffolds

In the context of new scaffolds obtained by photochemical reactions, Paternò-Büchi reactions between heteroaromatic, trifluoromethylphenyl ketone and electron rich alkenes to give oxetanes are described. A comprehensive study has then been carried out on the reaction of aromatic ketones with fluorinated alkenes. Depending on the substitution pattern at the oxetane ring, a metathesis reaction is described as a minor side process to give mono fluorinated alkenes. Overall, this last reaction corresponds to a photo-Wittig reaction and yield amid isosteres. In order to explain the uncommon regioselectivity of the Paternò-Büchi reaction with these alkenes, electrostatic-potential derived charges (ESP) have been determined. In a second computational study, the relative stabilities of the typical 1,4-diradical intermediates of the Paternò-Büchi reaction have been determined. The results well explain the regioselectivity. Further transformations of the oxetanes or previous functionalization of the fluoroalkenes open perspectives for oxetanes as core structures for biologically active compounds.     

Photoredox‐Catalyzed Functionalization of Alkenes with Thiourea Dioxide: Construction of Alkyl Sulfones or Sulfonamides

Sulfonylation of alkenes through photoredox‐catalyzed functionalization of alkenes with thiourea dioxide under visible‐light irradiation is achieved. The reaction of alkenes, thiourea dioxide and electrophiles provides a green and efficient access to alkyl sulfones and sulfonamides. A broad reaction scope is presented with good functional group compatibility and excellent regioselectivity. A plausible mechanism involving a radical addition process with sulfur dioxide radical anion (SO₂^‐) derived from the oxidation of sulfur dioxide anion (SO₂^2–) is proposed, which is supported by fluorescence quenching experiments.     

A synthesis of trisubstituted alkenes by a Ru-catalyzed addition

Catalyzed by ruthenium trisacetonitrile hexafluorophosphate 4, the Alder-ene type reaction of alkenes and internal alkynes provides an effective way to synthesize trisubstituted alkenes. Unlike most typical olefination protocols, this reaction is atom economical, and affords trisubstituted alkenes with defined olefin geometry. The regioselectivity can be explained invoking a steric argument based on the proposed mechanism. The first C-C bond formation generally involves sterically less hindered carbons of the alkenes and alkynes. Modest to very high regioselectivity can be achieved depending on the steric difference of the two substituents of alkynes.     

Iridium‐Catalyzed Distal Hydroboration of Aliphatic Internal Alkenes

The regioselective hydroboration of aliphatic internal alkenes remains a great challenge. Reported herein is an iridium‐catalyzed hydroboration of aliphatic internal alkenes, providing distal‐borylated products in good to excellent yields with high regioselectivity (up to 99:1). We also demonstrate that the C?B bond of the distal‐borylated product can be readily converted into other functional groups. DFT calculations indicate that the reaction proceeds through an unexpected Ir^III/Ir^V cycle.     

A radical procedure for the anti-Markovnikov hydroazidation of alkenes

A one-pot procedure for the efficient hydroazidation of alkenes involving hydroboration with catecholborane followed by reaction with benzenesulfonyl azide in the presence of a radical initiator is described. The regioselectivity is controlled by the hydroboration step and corresponds in most cases to an anti-Markovnikov regioselectivity. This procedure is applicable to a wide range of alkenes and gives excellent results with 1,2-disubstituted and trisubstituted alkenes.