亲核性氟源在碳碳不饱和键选择性氟化官能化反应中的应用

含氟化合物表现出的特殊理化和生物活性使得其在药物、农用化学品和材料科学等领域有着广泛而重要的应用,因此,含氟化合物的高效制备不仅成为了合成化学的研究热点之一,而且极大地推动了相关领域的蓬勃发展.其中,在有机分子内直接引入氟原子的方法主要有亲电氟化和亲核氟化.相较于亲电氟化,亲核氟化反应所用的氟化试剂通常廉价易得,所需的反应条件也比较温和.作者课题组借助过渡金属催化、可见光氧化还原催化和可见光促进策略,拓展了亲核性氟源在碳碳不饱和键选择性氟化官能化反应中的应用,合成了一系列结构新颖的含氟化合物.在该研究评论中将对此做出小结,并对该领域值得关注的研究方向进行简要的展望.     

硝酸盐促进的温和通用的碳氢键氟化反应

正由于氟原子的特殊性质,有机物中引入氟元素可以显著提高其脂溶性、稳定性以及生物活性.正因为如此,近几十年来,有机含氟化合物越来越多地出现在医药、农药以及材料等领域.与传统的氟化反应相比,通过碳氢键活化构建碳氟键是最有效直接地引入氟原子的手段,也是目前研究的热点.尽管如此,当前已有的为数不多的几例碳氢键     

过渡金属催化C—H键氟化反应研究进展

有机氟化物由于其特殊的性质被广泛应用于医药、农药以及材料领域中,然而由于氟元素的强电负性使得引入氟原子充满了挑战.过渡金属催化的碳氢键氟化反应由于其避免了使用预官能化的底物,而且对自然界中最广泛存在的碳氢键进行直接活化官能化,因此与传统的过渡金属催化的偶联反应相比在原子经济性、反应多样性以及环境友好性等方面都具有突出的优势.近十年来,利用过渡金属催化碳氢键氟化策略已经成为构建碳氟键重要手段和研究热点.作者较全面地综述近年来过渡金属催化的碳氟键构建的研究进展及合成应用,对该领域所存在的问题和局限性进行了总结,并对今后的发展做了展望.     

过渡金属促进的二氟烷基化和一氟烷基化反应研究进展

过渡金属参与的氟烷基化反应是当前有机氟化学研究的一个热点. 在过去的五年里, 由于新试剂新方法的发展, 过渡金属促进的全氟烷基化反应取得了长足的发展. 与全氟烷基化相比, 二氟和一氟烷基化反应不但可以方便地向分子中引入一个或几个氟原子, 还可以同时引入其它官能团, 因此在合成的步骤经济性上具有比直接氟化更大的优势. 尽管过渡金属促进的二氟和一氟烷基化反应是伴随着全氟烷基化反应而发展起来的, 在反应形式上与后者有很多相似之处, 但是二氟和一氟烷基化反应发展相对缓慢, 仍然存在发展空间. 在这篇综述里面, 我们首次全面地总结了过渡金属促进的二氟和一氟烷基化反应在过去近三十年时间里的发展进程. 全文包括五部分: 第一部分是引言, 从总体上介绍了二氟和一氟烷基化在氟化学中的地位; 第二、三两部分着重把官能团化的二氟烷基化反应和一氟烷基化反应按照反应的种类(即: 不饱和卤代烃的氟烷基化、不饱和体系碳-氢键氟烷基化、有机硼以及金属试剂的氟烷基化、不饱和碳-碳键的加成)进行了梳理; 第四部分为了强调二氟和一氟甲基化在氟烷基化中的重要地位, 将其单独介绍; 最后一部分是总结和展望.     

钯催化苯乙烯类分子胺氟化反应研究

报道了烯烃分子间的氧化双官能团化反应, 用金属钯作为金属催化剂, 三价碘为氧化剂, 氟化银为氟源, 磺酰胺类为亲核试剂, 实现了苯乙烯的分子间胺氟化反应, 得到α-F代苯乙胺类化合物; 反应是经过烯烃的反马氏氮钯化得到碳钯键, 再经过三价碘氧化成高价钯的中间体来形成C—F键, 在分子中的特定位置引入氟原子. 该反应的一个特点是选择性地得到反马氏胺氟产物.     

羰基兼容的氟代反应及远端氟代脂肪酮合成的近期进展

含氟化合物在医药、农药以及材料领域有着广泛的应用, 然而温和而高效的构建sp³碳氟键却极具挑战性. 氟代脂肪酮类化合物是一类重要的含氟合成砌块. 本文将从碳氢键氟化、脱羧脱硼氟化、双键氟化、开环氟化四个方面简要概述近年来羰基兼容的氟代反应以及在合成远端氟代脂肪酮方面取得的重要进展.     

耐极端条件含氟材料的研究进展

耐极端条件材料是指能在普通碳氢材料不耐受的极端环境（如：高温≥ 200℃、低温≤-50℃、紫外辐射1000 h等）下正常使用的材料.而电负性最强的氟元素与碳形成的碳氟键是最强的分子键之一,引入氟原子的材料也展示出特别优异的各项性能,因此含氟化合物在耐极端条件材料方面的应用研究得到了广泛的关注.本文对耐极端条件含氟材料的发展历史、研究现状与发展趋势进行了综述.首先,对氟化方法,包括碳-氟键形成及断裂、氟对碳-碳键形成的影响以及多氟芳基化方法等进行了介绍.接着,介绍了满足锂同位素萃取的苛刻条件的含氟萃取剂,应用于航空、航天、汽车等领域的含氟耐热材料,以及应用于电子设备、通信领域的高性能含氟低介电常数材料的相关研究.将来如何进一步发展优化耐极端条件含氟材料,并将这些研究成果投入大规模使用是科研人员努力的方向.     

碳硼烷和碳硼炔金属配合物中金属-碳键的化学性质

碳硼烷和碳硼炔金属配合物中的金属-碳键具有不同于经典金属-碳键的化学性质.一方面,二十面体碳硼烷独特的电子和空间效应使得碳硼烷金属配合物中的金属-碳键不参与和不饱和分子的反应 另一方面,在一定条件下具有大空间位阻的碳硼笼可以诱导某些碳-碳偶联反应.然而,碳硼炔金属配合物中的金属-碳键能与多种不饱和分子发生反应,其反应模式取决于中心金属离子的电子构型.本文简要总结了我们近期在这方面的研究进展.     

氢氟酸盐和三价碘实现的β,γ-不饱和羧酸脱羧氟化反应

介绍了一种基于氧化脱羧过程的合成含氟烯丙基化合物的新方法.利用三乙胺三氢氟酸盐为氟化试剂,在碘苯二乙酸为氧化剂的条件下,对β,γ-不饱和羧酸进行脱羧氟化,反应收率53%～76%.并且开发了一系列含氟烯丙基化合物的应用方法,包括环加成、氧化、还原以及通过活化烯烃实现的氟原子的取代反应（构建C―O,C―S,C―Se,C―N键）.     

应用苄位C—H氟化形式合成α,β-二氟代-γ-氨基酸（英文）

苄位C—H氟化已经成为一种向分子内引入氟原子的重要手段,然而,苄位C—H氟化反应还没有被应用到任何多步合成中.由于氟的构象效应,α,β-二氟代-γ-氨基酸在生物化学中有着重要的应用,但是其合成却具有一定的挑战性.在本文中,苄基C—H氟化作为关键步骤被成功用于syn-α,β-二氟代-γ-氨基酸1的形式合成.基于以下原因,本工作的合成路线比文献中的路线更为实用:(1)没有使用具有腐蚀性和毒性的亲核氟代试剂;(2)总收率为18%(以前的方法约为5%);(3)关键苄位C—H反应被放大到了克量级.在对反应进行优化的过程中,观察到明显的氟效应,即对于苄位C—H氟化反应,邻位含有氟原子的碳比普通碳反应活性低很多.     

Current and future developments of synthetic methods in organofluorine chemistry

Although fluorine chemistry is rapidly approaching its 100th anniversary, organofluorine chemistry, as most of us know it, is only 40–50 years old. Interest and enthusiasm in this area of chemistry essentially traces its origins to the discovery and industrial applications of the Freons and polytetrafluoroethylene (Teflon). The unique properties of these materials attracted attention to this neglected area of organic chemistry—particularly industrially—and stimulated work on methods for the introduction of fluorine into organic molecules.     

Fluorinated Rings: Conformation and Application

The introduction of fluorine atoms into molecules and materials across many fields of academic and industrial research is now commonplace, owing to their unique properties. A particularly interesting feature is the impact of fluorine substitution on the relative orientation of a C−F bond when incorporated into organic molecules. In this Review, we will be discussing the conformational behavior of fluorinated aliphatic carbo- and heterocyclic systems. The conformational preference of each system is associated with various interactions introduced by fluorine substitution such as charge-dipole, dipole-dipole, and hyperconjugative interactions. The contribution of each interaction on the stabilization of the fluorinated alicyclic system, which manifests itself in low conformations, will be discussed in detail. The novelty of this feature will be demonstrated by presenting the most recent applications.     

Platinum(II)-catalyzed cross-coupling of polyfluoroaryl imines

The introduction of fluorine into an organic molecule imparts unique physicochemical properties. Not surprisingly, fluorine is increasingly incorporated into new drugs and agrochemicals. However, aryl fluoride building blocks are only available through synthesis. The ability to cross-couple polyfluoroaromatics selectively could provide a convenient route to functionalized fluoroaromatics. We report herein the first examples of Pt-catalyzed cross-coupling of aryl fluorides. The methylated products can potentially serve as precursors to a wide range of functionalized fluorinated small molecules.     

Effective design of A-D-A small molecules for high performance organic solar cells via F atom substitution and thiophene bridge

Novel A-D-A-type small molecule donors employ thiophene bridge and F-substitution to improve the power conversion efficiency in organic solar cell.     

Selectfluor: Mechanistic Insight and Applications

The replacement of hydrogen atoms with fluorine substituents in organic substrates is of great interest in synthetic chemistry because of the strong electronegativity of fluorine and relatively small steric footprint of fluorine atoms. Many sources of nucleophilic fluorine are available for the derivatization of organic molecules under acidic, basic, and neutral conditions. However, electrophilic fluorination has historically required molecular fluorine, whose notorious toxicity and explosive tendencies limit its application in research. The necessity for an electrophilic fluorination reagent that is safe, stable, highly reactive, and amenable to industrial production as an alternative to very hazardous molecular fluorine was the inspiration for the discovery of selectfluor. This reagent is not only one of the most reactive electrophilic fluorinating reagents available, but it is also safe, nontoxic, and easy to handle. In this Review we document the many applications of selectfluor and discuss possible mechanistic pathways for its reaction.     

Selectfluor: mechanistic insight and applications

The replacement of hydrogen atoms with fluorine substituents in organic substrates is of great interest in synthetic chemistry because of the strong electronegativity of fluorine and relatively small steric footprint of fluorine atoms. Many sources of nucleophilic fluorine are available for the derivatization of organic molecules under acidic, basic, and neutral conditions. However, electrophilic fluorination has historically required molecular fluorine, whose notorious toxicity and explosive tendencies limit its application in research. The necessity for an electrophilic fluorination reagent that is safe, stable, highly reactive, and amenable to industrial production as an alternative to very hazardous molecular fluorine was the inspiration for the discovery of selectfluor. This reagent is not only one of the most reactive electrophilic fluorinating reagents available, but it is also safe, nontoxic, and easy to handle. In this Review we document the many applications of selectfluor and discuss possible mechanistic pathways for its reaction.     

Stereocontrolled Synthesis of Functionalized Azaheterocycles from Carbocycles through Oxidative Ring Opening/Reductive Ring Closing Protocols

Fluorine‐containing organic scaffolds are of significant interest in medicinal chemistry. The incorporation of fluorine into biomolecules can lead to remarkable changes in their physical, chemical, and biological properties. There are already many drugs on the market, which contain at least one fluorine atom. Saturated functionalized azaheterocycles as bioactive substances have gained increasing attention in pharmaceutical chemistry. Due to the high biorelevance of organofluorine molecules and the importance of N‐heterocyclic compounds, selective stereocontrolled procedures to the access of new fluorine‐containing saturated N‐heterocycles are considered to be a hot research topic. This account summarizes the synthesis of functionalized and fluorine‐containing saturated azaheterocycles starting from functionalized cycloalkenes and based on oxidative ring cleavage of diol intermediates followed by ring expansion with reductive amination.     

Palladium-Catalyzed Arylfluorination of Alkenes: A Powerful New Approach to Organofluorine Compounds

Fluorine incorporation into organic molecules is often beneficial to their absorption, distribution, metabolism, and excretion (ADME) properties or bioactivity. As a consequence, organofluorine compounds have become quite common amongst drugs and agrochemicals, and their preparation is a highly important topic in both synthetic organic chemistry and pharmaceutical chemistry. One of the newly developed methods for accessing organofluorine compounds is Pd-catalyzed arylfluorination of alkenes. It is an olefin difunctionalization process that simultaneously introduces an aryl group and a fluorine atom into an alkene framework. This review provides a concise overview of this powerful and versatile method.     

Effect of fluorination on the electronic structure and optical excitations of pi-conjugated molecules

Fluorination of pi-conjugated organic molecules is a strategy to obtain possible n-type conducting and air-stable materials due to the lowering of the frontier molecular orbitals (MOs) by the high electronegativity of fluorine. Nevertheless, the resulting optical gaps may be widened or narrowed, depending on the molecular backbone and/or the number and position of the fluorine atoms. The authors have performed time-dependent density functional theory calculations to address the subtle influence of fluorine substitution on the absolute MO energies and the subsequent impact on the optical transitions in homologous conjugated oligomers based on thiophene and acene units.     

Adsorption and sequential thermal release of F2, Cl2, and Br2 molecules by a porous organic cage material (CC3-R): Molecular dynamics and grand-canonical Monte Carlo simulations

The adsorption–desorption behavior of fluorine, chlorine, and bromine molecules onto a crystalline porous organic cage, namely CC3-R was calculated at different temperatures using molecular dynamics (MD) and grand-canonical Monte Carlo (GCMC) simulations. Self-diffusion coefficients, radial distribution functions (RDF), and adsorption isotherms were calculated for this purpose. The results show that CC3-R has varied capacities to capture these halogens at ambient and high temperatures, so that the thermal release of fluorine is completed with increasing temperature up to around 70°C and chlorine molecules remain at the CC3-R surface up to 100°C and all bromine molecules are removed from the CC3-R surface at 200°C. We found that bromine self-diffusion was almost independent of temperature between 0 and 100°C in contrast to fluorine and chlorine. Among different diffusion regimes, Knudsen diffusion appears to have an important role in the adsorption of heavy halogens at higher temperatures.