直接三氟甲硫基化反应研究进展

三氟甲硫基由于具有较强的吸电子性和极高的亲脂性,使得含三氟甲硫基的化合物在医药、农药以及材料等领域发挥着重要的作用.从有机氟化学的发展历程来看,三氟甲硫基化反应是继三氟甲基化反应后的又一重要研究课题,受到化学家的广泛关注.重点论述了近5年来国内外学者在直接三氟甲硫基化反应的研究成果,并讨论了三氟甲硫基化反应所面临的一些挑战.     

三氟甲硫基化反应的研究进展

由于三氟甲硫基具有强吸电子性和高亲脂性,含三氟甲硫基的化合物在医药和农药等领域具有重要的应用价值,因此发展向有机分子引入三氟甲硫基的方法已成为当前有机氟化学领域的热点研究课题之一。本文根据三氟甲硫基化试剂的性质总结了近5年在直接三氟甲硫基化反应研究领域取得的研究成果,包括新的三氟甲硫基化试剂以及新的合成方法在直接三氟甲硫基化反应中的应用。     

基于二氟卡宾转化的芳基和烯基碘化物的三氟甲硫基化

二氟卡宾在有机氟化物的合成中发挥了重要作用.之前的发现,二氟卡宾能与硫单质反应产生硫代氟光气,这对二氟卡宾化学的新发现以及硫代氟光气的应用研究都具有重要价值.利用这一路径已经实现了端基炔烃和烷基卤化物的三氟甲硫基化.在此,继续深入研究这一路径在合成上的应用,并实现了芳基和烯基碘化物的三氟甲硫基化.三氟甲硫基化是有机氟化学的一个重要研究方向,常用方法一般需要使用含CF₃S基团的昂贵试剂.在该方法中, CF₃S基团是由二氟卡宾、硫单质和氟离子现场产生的,所用试剂都廉价易得.     

钯催化的芳基C-H键三氟甲硫基化反应

报道了二价钯催化的高选择性芳基C-H键的三氟甲硫基化反应,其中稳定的三氟甲硫基苯胺2a作为三氟甲硫基试剂,醋酸钯作为催化剂,苯甲酰氯和醋酸银作为添加剂,反应在DMF中120℃条件下实现的.各种取代的吡啶都可以作为该反应的导向基团.反应中苯甲酰氯的添加对活化三氟甲硫基苯胺2a起着关键作用.该反应为合成邻位三氟甲硫基取代苯类衍生物提供了高效方便的方法.     

直接三氟甲硫基化试剂及方法的研究进展

三氟甲硫基脂溶性高、吸电子能力强,将其引入药物分子中可以改变分子药代动力学以及物理化学特性,提高代谢稳定性.含三氟甲硫基的分子在医药、农药、材料以及含氟日用品等领域得到了广泛的应用.因此,如何高效地向分子中引入三氟甲硫基团成为了近些年来有机氟化学领域的一个研究热点.经过几年的研究,新的三氟甲硫基化试剂及方法得到了快速的发展,为药物化学家提供了方便简洁地引入三氟甲硫基团的工具箱.在本篇综述中,将首先简要介绍间接引入三氟甲硫基团的方法,随后将对直接引入三氟甲硫基团的方法,尤其是近些年来发展的过渡金属催化、亲电三氟甲硫基化以及自由基类型的三氟甲硫基化方法做着重的介绍.最后将对三氟甲硫基化领域存在的问题和难点进行简要的展望.     

通过远端碳氮双键迁移实现非活化烯烃的三氟甲硫基化反应

利用自由基参与的官能团迁移策略实现了非活化烯烃的三氟甲硫基化反应.通过AgSCF₃和K₂S₂O₈相互作用产生的三氟甲硫基自由基与非活化烯烃反应,继而诱导远端含有碳氮双键官能团（杂芳基、亚胺）的分子内迁移,从而实现非活化烯烃的三氟甲硫基化反应.该转化具有反应条件温和、产物收率高、官能团兼容性广及区域选择性单一等特点,对具有不同电性和位阻的底物具有较好的适用性,高效构建了一系列含有三氟甲硫基的烷烃酮化合物.     

无金属催化芳基亚磺酸钠的三氟甲硫基化反应

以N-三氟甲硫基苯胺为三氟甲硫基化试剂,乙腈为溶剂,在对甲基苯磺酸促进下,于室温反应6~8 h,实现了芳基亚磺酸钠的三氟甲硫基化反应,目标产物结构经~1H NMR,~(19)F NMR和HR-MS(ESI)确证。     

对三氟甲硫基苯酚的合成研究

在偶极性质子溶剂N ,N 二甲基甲酰胺中 ,以对羟基苯硫酚为底物 ,硫代硫酸钠为自由基引发剂促进CF3 Br产生·CF3 ,·CF3 与底物反应生成对三氟甲硫基苯酚。实现了以CF3 Br为试剂进行三氟甲硫基化的合成路线。反应混合物经简单蒸馏后 ,得到的产物三氟甲硫基苯酚含量达 98% ,收率 81 .5 %。     

不对称三氟甲硫基化反应研究进展

三氟甲硫基吸电子能力强、脂溶性高,在药物分子内引入三氟甲硫基可以显著地提高化合物的细胞膜穿透性与代谢稳定性.而不同立体异构的药物分子会有不同的药理活性,因此不对称三氟甲硫基化反应在近几年内逐渐受到化学家们的重视.目前,这一领域还处于发展的初步阶段,本文将就目前为止已经发展的不对称三氟甲硫基化方法做简单的总结,包括使用亲电的三氟甲硫基试剂和使用含三氟甲硫基的合成砌块这两种不同的策略.最后对不对称三氟甲硫基化领域所存在的挑战进行简单的展望.     

醇的直接脱羟三氟甲硫基化反应

<正>Angew.Chem.Int.Ed.2015,54,897~900三氟甲硫基(CF3S)是强吸电子和最强亲脂基团,因此含三氟甲硫基的化合物在药物和农药研制中有着广泛的应用.近二年来,发展向有机分子引入三氟甲硫基是继三氟甲基化反应后有机氟化学领域的热点研究课题之一,但目前的工作主要集中于芳基三氟甲硫醚化合物的合成.中国科学院上海有机化学研究所卿凤翎课题组发展了醇的直接脱羟三氟甲硫基化反应.三氟甲硫基负离子不稳定,它会分解生成硫氟光气A和氟负离子.卿凤翎等认为新生成的     

PhSO2SCF2H: A Shelf‐Stable,Easily Scalable Reagent for Radical Difluoromethylthiolation

A new shelf‐stable and easily scalable difluoromethylthiolating reagent S‐(difluoromethyl) benzenesulfonothioate (PhSO₂SCF₂H) was developed. PhSO₂SCF₂H is a powerful reagent for radical difluoromethylthiolation of aryl and alkyl boronic acids, decarboxylative difluoromethylthiolation of aliphatic acids, and a phenylsulfonyl‐difluoromethylthio difunctionalization of alkenes under mild reaction conditions.     

PhSO2SCF2H: A Shelf‐Stable,Easily Scalable Reagent for Radical Difluoromethylthiolation

A new shelf‐stable and easily scalable difluoromethylthiolating reagent S‐(difluoromethyl) benzenesulfonothioate (PhSO₂SCF₂H) was developed. PhSO₂SCF₂H is a powerful reagent for radical difluoromethylthiolation of aryl and alkyl boronic acids, decarboxylative difluoromethylthiolation of aliphatic acids, and a phenylsulfonyl‐difluoromethylthio difunctionalization of alkenes under mild reaction conditions.     

一氟甲基二硫化物的高效合成

以PhSO₂SCH₂F为一氟甲硫基化试剂,室温下实现了硫酚/硫醇的一氟甲硫基化反应,高收率地合成了一系列一氟甲基二硫化物.该方法具有反应时间短、条件温和、操作简单以及无需外加添加剂等特点,为高效制备一氟甲基二硫化物提供了一条简便的途径.     

Copper‐Promoted Sandmeyer Difluoromethylthiolation of Aryl and Heteroaryl Diazonium Salts

An efficient copper‐promoted difluoromethylthiolation of aryl and heteroaryl diazonium salts is described. The reaction is conducted under mild reaction conditions and various functional groups were compatible. In addition, reactions of heteroaryl diazonium salts such as pyridyl, quinolinyl, benzothiazolyl, thiophenyl, carbazolyl, and pyrazolyl diazonium salts occurred smoothly to afford the medicinally important difluoromethylthiolated heteroarenes. Furthermore, a more practical one‐pot direct diazotization and difluoromethylthiolation protocol was developed, and it converts the aniline derivatives into difluoromethylthiolated arenes. The utility of the method is demonstrated by difluoromethylthiolation of a number of natural products and drug molecules.     

含巯基(-SH)糖的合成及其应用研究进展

含巯基(-SH)糖是一类重要的糖类化合物,其作为天然糖的结构类似物在生物医药领域具有十分重要的作用。本综述以六碳糖为例介绍了糖的不同位置上含巯基(-SH)糖的合成方法,根据合成含巯基(-SH)糖的硫源不同,对所报道的反应进行分类,并介绍了巯基脱保护基的方法。同时还概述了近年来在过渡金属催化剂作用下,含巯基糖与芳基卤化物的偶联反应。     

New Syntheses of Diazo Compounds

Diazo compounds (R¹R²C?N₂) are known as versatile and useful substrates for an array of chemical transformations and, therefore, diazo chemistry is still far from losing anything of its long‐standing fascination. In addition to many studies on the subsequent chemistry of the diazo group, the inventory of methods for the preparation of diazo compounds is continuously supplemented by new methods and novel variations of established procedures. Several of these synthetic approaches take into account the lability and remarkable chemical reactivity of certain classes of diazo compounds, and environmentally more benign procedures also continue to be developed.     

ADSORPTION OF PHENOL AND Pb^2＋ FROM AQUEOUS SOLUTIONS BY A NEW DI-FUNCTION ADSORBENT WITH SULFHYDRYL GROUPS

A new di-function adsorbent （JN-3） was prepared by sulfhydryl modified. Comparing with Amberlite XAD-4 and NDA-150, the equilibrium adsorption for phenol on the JN-3 from aqueous solutions was tested, perfect adsorption capacity was shown. Pb^2＋ can be also removed by JN-3 because of the chelate interaction between sulfhydryl groups and metal ions. This adsorbent could be used in removal of combine pollutants such as phenolic compounds and heavy metal ions from waste streams.     

Chiral Compounds Synthesized by Biocatalytic Reductions [New Synthetic Methods (51)]

It has been known for many decades that chiral compounds can be obtained by stereospecific biocatalytic reduction. Further significant methodological developments in this field have, however, only been made during the past ten years; they include the application of previously unused microorganisms and electron donors, the discovery of additional substrates for the known reductases, the development of methods for regenerating reduced pyridine nucleotides, and the discovery of new reductases which were sought for specific preparative purposes. Many chiral compounds can now be synthesized by microbial hydrogenation using H₂ and hydrogenase-containing microorganisms as well as by electromicrobial or electroenzymatic reduction. In the two latter methods, anaerobic or aerobic organisms are supplied with electrons from electrochemically reduced, artificial mediators, e.g., methyl viologen. Reductases that do not require pyridine nucleotides and can accept electrons directly from reduced viologens are especially useful. Two examples of this type of enzyme are described which are of preparative interest. Many cells contain methyl viologen-dependent NAD(P) reductases, a large number of which have still not been characterized. A productivity number is proposed which allows different methods of bioconversion with microorganisms to be compared. The productivity numbers of compounds synthesized by the methods described in this review are often 10- to 100-fold higher than those of substances obtained by conventional techniques.     

Carbon Nanotube‐Adsorbed Electrospun Nanofibrous Membranes as Coating for Electrochemical Sensors for Sulfhydryl Compounds

A new method to modify electrodes with carbon nanotubes (CNT) was developed. Multiwalled carbon nanotubes (MWNT) were adsorbed on the electrospun nylon‐6 nanofibrous membranes (Ny‐6‐NFM) and used as a coating to modify conventional glassy carbon electrodes. The modified electrode was designed for the amperometric detection of sulfhydryl compounds with the potential held at +0.3 V vs. Ag/AgCl. The modified electrode showed a linear response for cysteine up to 0.4 mM (R²=0.997), with a sensitivity of 5.1 µA/mM and a detection limit of 15 µM. Other sulfhydryl compounds showed similar results. After use, the Ny‐6‐NFM was easily peeled off, leaving the bare electrode surface back to its original electrochemical behaviour. This is the first attempt to use a disposable membrane functionalized with MWNT for electroanalytical purposes.     

New synthesis and reactions of perfluoro-tert-butyl chloroformate

A new synthesis of perfluoro-tert-butyl chloroformate (perfluoro-tert- butoxycarbonyl chloride) is based on the reaction of potassium perfluoro- tert-butoxide with one equivalent of phosgene in xylene or mesitylene. Perfluoro-tert-butyl chloroformate reacts readily with hydroxy, sulfhydryl and amino compounds to give the corresponding perfluoro-tert-butyl alkyl carbonates, thiolcarbonates or carbamates, respectively. Dialkyl carbonates, diaryl carbonates, and symmetrically substituted ureas are formed as by-products and, with some compounds, as exclusive products. Primary amines form isocyanates.