Reactions Using Freons and Halothane as Halofluoroalkyl/Halofluoroalkenyl Building Blocks

In recent years, hydrofluorocarbon compounds such as chlorofluorocarbons, hydrochlorofluorocarbons, and 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane) have been used as fluorine-containing building blocks to construct functional fluorine-containing compounds, e. g., polymers, liquid crystals, and medicines. Hydrofluorocarbons promote the formation of reactive fluoroalkyl or fluoroalkenyl species via anionic or radical processes, and these species can act as nucleophiles or electrophiles depending on the reaction conditions. Progress in fluorine chemistry using hydrofluorocarbons in the last 30 years is described in this review and diverse reactions are discussed, including the fluoroalkyl/alkenyl products and proposed mechanisms involved.     

Fluoroalkyl N-sulfonyl hydrazones: An efficient reagent for the synthesis of fluoroalkylated compounds

Fluoroalkyl N-sulfonyl hydrazones are versatile reagents that can be used to synthesize a wide range of diverse fluoroalkylated organic molecules. Although it has been known since 1975, the chemistry of fluoroalkyl N-sulfonyl hydrazones has recently only received great attention from the scientific community. Generally, they are used as either safe and bench-stable diazo precursors in carbene transfer reactions or as 1,3-dipoles in cycloaddition and cyclization reactions. Notably, fluoroalkyl N-sulfonyl hydrazones to replace toxic fluoroalkyl diazo compounds in carbene transfer reactions reduce the risk of rapid accumulation of explosive diazo compounds and improve functional group compatibility and substrate scope. Given the growing importance of fluoroalkyl N-sulfonyl hydrazones in chemical synthesis, a comprehensive review of this topic in the literature is essential to demonstrate their synthetic potential. In this review, we critically summarize and comprehensively analyze the publications in various literatures on the chemistry of fluoroalkyl N-sulfonyl hydrazones starting from 1990 to date. The classification of the different reactivity profiles of fluoroalkyl N-sulfonyl hydrazones and the efficiencies of similar types of reactions or substrates with fluoroalkyl diazo compounds are compared.     

Merging Fluorine Incorporation and Functional Group Migration

Fluorine incorporation by concomitant fluoroalkyl radical addition to alkene or alkyne and functional group migration (FGM) represents an ingenious and robust strategy for the synthesis of structurally diverse fluorinated compounds. This account gives an overview of related studies in our group, in which three main reaction modes are discussed: 1) radical fluoroalkylative difunctionalization of unactivated alkenes via intramolecular FGM; 2) alkene difunctionalization by docking-migration process using fluoroalkyl-containing bifunctional reagents; 3) incorporation of fluoroalkyl group into C(sp³)−H bond via consecutive hydrogen atom transfer (HAT) and FGM. Relying on these methods, a variety of trifluoromethylation and di-/mono-fluoroalkylation reactions along with the migration of cyano, heteroaryl, oximino, formyl, alkynyl, and alkenyl groups have been accomplished under mild conditions.     

Synthesis of fluorinated amino acid derivatives through late-stage deoxyfluorinations

Fluorine chemistry has represented a hot topic in drug research over the last decade. Because of their pharmaceutical potential, fluorine-containing amino acids and related derivatives have acquired high importance among medicinal chemists. Therefore their synthesis and the development of various synthetic methods for these types of molecular scaffolds have gained increasing interest in synthetic organic chemistry. The current review focuses on synthetic protocols towards fluorine-containing amino acid derivatives through late-stage fluorination with various nucleophilic reagents, describing the access of various open-chain and cyclic α-, β-, γ-amino acid derivatives.     

Phosphorus containing mixed anhydrides--their preparation, labile behaviour and potential routes to their stabilisation

Simple mixed anhydrides are known to pose synthetic difficulties relating to their thermal lability and ways to stabilise such mixed anhydride systems by relying on either electronic or steric effects were therefore explored. Thus, a series of acyloxyphosphines and acylphosphites derived from either propanoic acid or phenylacetic acid were prepared and their in solution stability assessed. These compounds were, where stability allowed, fully characterised using standard analytical techniques. NMR studies, in particular, unearthed interesting coupling behaviour for a number of the acyloxyphosphines and acylphosphites as well as their rearrangement products which could be linked to their chiral nature. Furthermore, the crystal structures for three of the prepared mixed anhydrides were determined using X-ray crystallography and are reported herein.     

含氟活泼亚甲基类化合物的研究

本研究工作包括下列三个方面的内容：（1）双-（全氟烷砜基）甲烷,双-（ 三氟双酰基）甲烷的合成及其反应。（2）2-氟烷基取代的醛和酮的合成和反应。 （3）氟烷基取代的1,3-二羰基化合物的化学转化及其在合成含氟杂环化合物中的 应用。     

Fluorine transfer to alkyl radicals

The development of new synthetic technologies for the selective fluorination of organic compounds has increased with the escalating importance of fluorine-containing pharmaceuticals. Traditional methods potentially applicable to drug synthesis rely on the use of ionic forms of fluorine (F(-) or F(+)). Radical methods, while potentially attractive as a complementary approach, are hindered by a paucity of safe sources of atomic fluorine (F(?)). A new approach to alkyl fluorination has been developed that utilizes the reagent N-fluorobenzenesulfonimide as a fluorine transfer agent to alkyl radicals. This approach is successful for a broad range of alkyl radicals, including primary, secondary, tertiary, benzylic, and heteroatom-stabilized radicals. Furthermore, calculations reveal that fluorine-containing ionic reagents are likely candidates for further expansion of this approach to polar reaction media. The use of these reagents in alkyl radical fluorination has the potential to enable powerful new transformations that otherwise would take multiple synthetic steps.     

Synthesis of 3-Trifluoromethyl-4-halobenzonitriles

The practical synthetic method for a series of substantially novel fluorine-containing polyfunctional aromatic compounds, 3-trifluoromethyl-4-halobenzonitriles [halo = Cl, Br, and F], was established by using copper-cyano complexes as effective Sandmeyer cyanating reagents.     

Transition Metals in the Synthesis and Functionalization of Indoles [New Synthesis Methods (72)]

The use of transition-metal complexes as reagents for the synthesis of complex organic compounds has been under development for at least several decades, and many extraordinary organic transformations of profound potential have been realized. However, adoption of this chemistry by the practicing synthetic organic chemist has been inordinately slow, and only now are transition-metal reagents beginning to achieve their rightful place in the arsenal of organic synthesis. Several factors contributed to the initial reluctance of synthetic organic chemists to use organometallic reagents. Lacking education and experience in the ways of elements having d electrons, synthetic chemists viewed organometallic processes as something mysterious and unpredictable, and not to be discussed in polite society. Organometallic chemists did not help matters by advertising their latest advances as useful synthetic methodology, but restricting their studies to very simple organic systems lacking any serious functionality (e.g., the “methyl, ethyl, butyl, futile” syndrome). Happily, things have changed. Organometallic chemists have turned their attention to more complex systems, and more recently trained organic chemists have benefited from exposure to the application of transition metals. This combination has set the stage for major advances in the use of transition metals in the synthesis of complex organic compounds. This review deals with one aspect of this area, the use of transition metals in the synthesis of indoles.     

Synthesis, reactions, and applications of fluorine-containing multifunctional carbon compounds

The chemistry of compounds containing a carbon atom bearing three or four different labile functional groups has received little attention. These compounds should be of considerable significance in theoretical and synthetic organic chemistry. Among the compounds with multifunctional structures, those having both carbonyl and halogen groups in addition to other heteroatom groups seem especially valuable from a synthetic viewpoint. Their potential use as probes in pure and applied synthetic chemistry has not been exploited, presumably because of structural instability and a paucity of synthetic approaches. Keeping this background in mind, we focused on the synthesis of a new class of multifunctional carbon compounds in which ester carbonyl, halogen, and other heteroatom-derived functional groups are directly attached to the central carbon atom. Fluorine was chosen as the halogen because of the inherent stability of the CF bond and because of the fundamental chemical and biological interest in fluorine-containing compounds. The synthesis, reactions, and some applications of various fluorine-containing multifunctional carbon compounds are described.     

超临界二氧化碳中含氟聚合物的合成

超临界二氧化碳是廉价、低毒、不易燃、易回收、环境友好的惰性聚合介质,是传统有机溶剂的替代品。尤其是有望成为含氟单体的聚合溶剂,以替代目前使用的氟氯烃。本文详细地介绍了近年来以超临界二氧化碳为介质的氟烷基丙烯酸酯类单体和氟烯烃类单体的聚合反应研究,其中涉及氟烷基丙烯酸酯类单体的均聚和共聚,可熔融加工的四氟乙烯聚合物,离子交换树脂,偏氟乙烯的均聚和共聚合等。研究表明在超临界二氧化碳中的含氟单体的聚合反应有其它溶剂体系无法比拟的优点。     

Polyanthranilides. I. Synthesis and Characterization of Polyamides from Isatoic Anhydrides

Ring-scission polymerization of simple and bz-nitro and bz-chlorosubstituted isatoic anhydrides is studied in the presence of reagents like aqueous HCl, anthranilamide, N-methyl aniline, o-chloroaniline, and acid amides under various reaction conditions. Only simple isatoic anhydride is found to undergo ring-scission polymerization affording polyanthranilides in the presence of the first four reagents under appropriate conditions. These samples are insoluble in all organic solvents including formic acid. They are characterized by IR spectral study and thermogravimetric and differential thermal analysis.     

Recent advances in fluorinated vinylstannanes and their synthetic utility

Fluorinated vinylstannanes have attracted much interest in recent years because they provided a useful and convenient methodology for the introduction of monofluoro, difluoro, trifluoro or polyfluoro functionality into organic molecules with retention of configuration, particularly in the synthesis of fluorine-containing naturally occurring compounds. The new methodologies discussed in this review are, therefore, potentially useful in organic synthesis particularly in the medicinal and agricultural chemistry for the synthesis of fluorine-containing biologically active compounds.     

Mild and Efficient Palladium‐Catalyzed Direct Trifluoroethylation of Aromatic Systems by C−H Activation

The introduction of trifluoroalkyl groups into aromatic molecules is an important transformation in the field of organic and medicinal chemistry. However, the direct installation of fluoroalkyl groups onto aromatic molecules still represents a challenging and highly demanding synthetic task. Herein, a simple trifluoroethylation process that relies on the palladium‐catalyzed C?H activation of aromatic compounds is described. With the utilization of a highly active trifluoroethyl(mesityl)iodonium salt, the developed catalytic method enables the first highly efficient and selective trifluoroethylation of aromatic compounds. The robust catalytic procedure provides the desired products in up to 95 % yield at 25 °C in 1.5 to 3 hours and tolerates a broad range of functional groups. The utilization of hypervalent reagents opens new synthetic possibilities for direct alkylations and fluoroalkylations in the field of transition‐metal‐catalyzed C?H activation.     

Gas-chromatographic determination of carboxylic acid anhydrides in oxidation products of alcohols and other organic compounds

A procedure was developed for the gas-chromatographic determination of carboxylic acid anhydrides in the composition of oxidation products of organic compounds after their conversion into alkyl formate by formic acid and benzyl alcohol or other primary alcohol introduced into the reaction medium. The reaction proceeds through the mixed anhydride, which is formed in situ from formic acid and the determined anhydride and is predominantly transformed into the corresponding alkyl formate in alcoholysis with alcohol. The potentialities of the procedure were illustrated by the determination of anhydrides in oxidation products of cyclohexane, cyclohexanone, and cyclohexanol.     

Understanding and Controlling Fluorinated Diacyl Peroxides and Fluoroalkyl Radicals in Alkene Fluoroalkylations

The demand for practical methods for the synthesis of novel fluoroalkyl molecules is increasing owing to their diverse applications. Our group has achieved efficient difunctionalizing fluoroalkylations of alkenes using fluorinated carboxylic anhydrides as user-friendly fluoroalkyl sources. Fluorinated diacyl peroxide, prepared in situ from carboxylic anhydrides, enables the development of novel reactions when used as a radical fluoroalkylating reagent. In this account, we aim to provide an in-depth understanding of the structure, bonding, and reactivity of fluorinated diacyl peroxides and radicals as well as their control in fluoroalkylation reactions. In the first part of this account, the physical properties and reactivity of diacyl peroxides and fluoroalkyl radicals are described. In the subsequent part, we categorize the reactions into copper-catalyzed and metal-free methods utilizing the oxidizing properties of fluorinated diacyl peroxides. We also outline examples and mechanisms.     

Stabilization of poly(vinyl chloride) with organotin compounds: Part VIII—Catalytic action of organic acids and anhydrides with organotin carboxylate

When maleic acid or maleic anhydride are added to a dichlorobutane solution of chlorohexene (as a model compound for allylic chlorides in poly(vinyl chloride)) and organotin carboxylates (maleates or laurate) heated at 80°C, the esterification reaction is strongly accelerated; moreover, the formation of hexadiene, which is the expected product of the competitive elimination reaction, is not observed. The reaction is first order with respect to both chlorohexene and the organic acid or anhydride, and may either be zero or first order with respect to the organotin carboxylate. ¹H-NMR spectra and solubility experiments indicate the formation of complexes between the organotin carboxylate and the organic acid or anhydride. A concerted mechanism between the chlorohexene and these complexes is suggested. A few experiments show that the addition of these organic acids or anhydrides to a PVC formulation leads to improvement of the thermal stability.Finally, other organic acids and anhydrides were also used to complex the organotin carboxylate in order to rule out the complexation mechanism and to discuss the activated complex.     

Cyclic Hypervalent Iodine Reagents for Atom‐Transfer Reactions: Beyond Trifluoromethylation

Hypervalent iodine compounds are privileged reagents in organic synthesis because of their exceptional reactivity. Among these compounds, cyclic derivatives stand apart because of their enhanced stability. They have been widely used as oxidants, but their potential for functional‐group transfer has only begun to be investigated recently. The use of benziodoxol(on)es for trifluoromethylation (Togni's reagents) is already widely recognized, but other transformations have also attracted strong interest recently. In this Review, the development in the area since 2011 will be presented. After a short summary of synthetic methods to prepare benziodoxol(on)e reagents, their use to construct carbon–heteroatom and carbon–carbon bonds will be presented. In particular, the introduction of alkynes by using ethynylbenziodoxol(on)e (EBX) reagents has been highly successful. Breakthroughs in the introduction of alkoxy, azido, difluoromethyl, and cyano groups will also be described.     

Asymmetric catalytic anhydride openings via carbon-based nucleophiles

The asymmetric desymmetrization of cyclic anhydrides via the addition of carbon-based nucleophiles has been the focus of considerable levels of interest because it leads to optically active products. Over the past 20 years, a variety of different catalytic asymmetric alkylation reactions have been developed for the desymmetrization of cyclic anhydrides using different metal reagents as nucleophiles and using chiral ligands. The purpose of this review is to provide an overview of significant developments in this field. ~ 2013 Fen-Er Chen. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.     

Enantioselective organocatalytic fluorination using organofluoro nucleophiles

Synthetic fluorinated compounds are enormously useful in areas such as materials, agrochemicals, pharmaceuticals and fine chemicals. While methods of electrophilic fluorination have been extensively developed to stereoselectively install fluorine atoms onto molecules, nucleophilic fluorination is a much less explored approach. Recently, several organofluoro reagents have been designed and used as nucleophiles in the asymmetric synthesis of fluorinated compounds, significantly expanding the scope of enantio-enriched fluorine-containing compounds that can be synthesised. Such organofluoro nucleophiles are particularly useful in organocatalytic transformations. In this review, recent advances in the application of organofluoro nucleophiles in organocatalysis are summarised.