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Fluoroalkylthio groups have received substantial attention in the past decade because of their unique physicochemical characteristics, and methods for incorporating these substituents into organic molecules have been rapidly developed in recent years. This account summarizes our efforts on the development of direct fluoroalkylthiolation with fluoroalkanesulfite derivatives, several innovative and efficient strategies for the fluoroalkylthiolation of various substrates have been disclosed, affording various valuable fluoroalkylthiolated compounds in good yields.

A green and scalable strategy has been developed for the synthesis of lignin-derived Zn single atom/N-codoped porous carbon (LCN@Zn-SAC) containing similar ZnNx sites with carbonic anhydrases. This catalyst exhibits superior activity on the α-alkylation of ketones with alcohols via borrowing hydrogen strategy (TON up to 15 h−1) than most of previously reported works. The dehydrogenation of benzyl alcohol is the rate-determining step based on kinetic experiment results. According to experimental and theoretical calculation results, Zn electron density is inversely proportional to reaction energy barriers, because Zn sites with less positive charge (ZnN4 and ZnN3C) in Zn-SACs display better borrowing hydrogen ability than other Zn sites. Furthermore, this catalyst can be recycled by simple centrifugation, which can be reused at least 8 runs with no obvious lose in activity. To the best of our knowledge, this is the first example of non-noble metal-SAC-catalyzed α-alkylation via borrowing hydrogen strategy.

A practical and efficient method to synthesize thiocarbamyl fluorides and isothiocyanates from amines with trifluoromethanesulfonyl chloride was developed. In the presence of the reducing agent triphenylphosphine and sodium iodide, thiocarbamyl fluorides and isothiocyanates were synthesized from secondary/primary amine in moderate to excellent yields, respectively. A broad scope of substrates and good functional group compatibility were observed.

Newly developed sulfonyl chloride-based regioselective chlorothiolation of alkenes has been disclosed; the reaction is compatible with a variety of functional groups and can be scaled up to the gram scale with no loss in yield. The employment of readily available reactants, mild reaction conditions, and high regioselectivity makes this process very practical. Mechanistic studies revealed a possible free radical reaction pathway.

A newly developed CF3SO2Na-based trifluoromethylation of secondary amines has been disclosed, and the method has been successfully extended to the configuration of perfluoroalkyl amines using RfSO2Na, complementing the established synthesis strategy of trifluoromethyl amines. Advantages of the method include good functional group tolerance, mild conditions, and inexpensive or easy-to-handle materials. Mechanistic probes indicate that the thiocarbonyl fluoride formed in situ is the key intermediate in the reaction.

A new method using a sodium selenite-based (NaO2SeR) direct selenylation reagent has been developed. NaO2SeR is odorless, shelf-stable, easy to handle, practical and scalable. Good yields and a broad functional group compatibility were observed when it was reacted with indoles, a furan, pyrrole and ketones under reductive conditions to afford the corresponding organoselenium products.

Trifluoromethanesulfinyl chloride (CF3 SOCl) has been introduced as a new reagent for C-H trifluoromethylthiolation of indoles, thiophenes, and ketones under catalyst-free conditions and in the absence of reductant. The disproportionation of CF3 SOCl to CF3 SO2 Cl and CF3 SCl provides two pathways for the trifluoromethylthiolation. Direct trifluoromethylthiolation with CF3 SCl or trifluoromethylsulfoxidation with CF3 SOCl is followed by reduction with CF3 SOCl. This reagent can be used to functionalize benzothiophenes, benzofurans, and indenes under the promotion of Ag2 CO3 . It can also be used for trifluoromethylthiolation of thiols and benzeneselenols, and 1,2-bifunctional chlorotrifluoromethylthiolation of indoles, styrenes, and alkyenes. The method can also be extended for difluorometylthiolation reactions using CF2 HSOCl.

A copper-catalyzed vicinal chloro-thiolation of alkynes with inexpensive and diversified sulfonyl chlorides RSO2Cl (R = aryl, alkyl) has been developed. This practical and scalable reaction could b...

In this paper, R404 refrigeration system is evaluated to understand the exergy characteristics of an indirect refrigeration system for R404A that adopted CO2 as a secondary refrigerant. This provides basic data for the optimal design of indirect refrigeration system for the R404A. The results are summarized as follows. It was confirmed that the system’s exergy loss increased as the R404A condensation temperature, the CO2 cooler temperature difference, and the CO2 mass flow rate increased under a fixed experimental condition. However, the system’s exergy loss decreased as the CO2 evaporation temperature increased. It was also found that the exergy loss of the R404A refrigeration system was higher than that of the CO2 secondary refrigerant system. It was also confirmed that total exergy loss of the R404A refrigeration system and the indirect refrigeration system tended to be inversely related to the coefficient of performance. Regardless of any experimental conditions, the exergy loss rate of components was the largest in the compressor, followed by the R404A condenser, the expansion valve, the internal heat exchanger, the CO2 cooler, the CO2 evaporator and the pump. Therefore, in conclusion, it is necessary to reduce exergy loss in the compressor and the R404A condenser to improve the overall performance of this system.

A practical and efficient monofluoromethylthiolation that employs the typical Bunte salt, sodium S-(fluoromethyl) sulfurothioate, as the sulfur source is described. This reagent reacts readily with a variety of aryl amines and aryl thiols. The high tolerance of functional groups demonstrates the potential of this reaction. In addition, this method is suitable for the late-stage monofluoromethylthiolation of complex bioactive molecules.

Metal-free trifluoroethylthiolation with fluorinated sulfinate salt NaSO2CH2CF3 under reductive conditions has been developed. The strategy enables the installation of the SCH2CF3 moiety efficiently to form a number of unexplored stable trifluoroethylthiolated heterocycles, arenes, and thiols, which have the potential to be a new series of fluorine-containing chemical entities for medicinal chemists.

An efficient copper-catalyzed C–X (X = S, Se) decarboxylative coupling of alkynyl carboxylic acids with Bunte salts has been developed. The process is amenable to various alkynyl carboxylic acids and Bunte salts and is compatible with a wide range of functional groups. In addition, this catalytic reaction could also be performed with seleno Bunte salts and alkynyl carboxylic acids under the same conditions, giving the alkynyl selenosulfides in good yields. Importantly, this route avoids the use of odorous thiol or selenol starting materials.

A straightforward one-pot synthesis of difluoromethyl thioethers from thiourea and diethyl bromodifluoromethylphosphonate has been developed. Thiourea is a cheap and friendly sulfur reagent, while diethyl bromodifluoromethylphosphonate is a low-cost and stable difluorocarbene precursor. The strategy enabled the introduction of SCF2H moieties into indoles, pyrroles, and activated arenes and formed a number of difluoromethyl thioethers.

A method for direct difluoromethylthiolation of Ar−H bonds is introduced. The stable and easy-to-handle HCF2SO2Na is reduced with (EtO)2P(O)H in the presence of TMSCl to generate HCF2S+ for the regioselective difluoromethylthiolation of aromatic compounds including indoles, pyrroles, and activated benzenes. This method is also applicable for the trifluoromethylthiolation with CF3SO2Na and the perfluoroalkylthiolation with RfSO2Na of arenes and heteroarenes. Reaction mechanisms associated with the metal-free electrophilic fluoroalkylthiolation reactions are also discussed.

A highly carbon-selective monofluoromethylation of a broad range of β-ketoesters with fluoromethyl iodide under mild conditions is described. The uses of lithium tert-butoxide as the base and diglyme as the solvent made great contributions to the high C/O regioselectivity.

A radical-mediated approach has been introduced for the C-S bond activation of arylalkenyl sulfides. The protocol provides an efficient approach for the generation of various alkenes including alkenyl silanes, sulfones, phosphine oxides, and nitroolefins. In most cases, these radical substitutions are performed under metal-free conditions with stereospecificity.

Copper-catalyzed fluoroalkylation of alkynes and alkynyl carboxylic acids has been achieved with high functional-group tolerance and excellent regio- and stereoselectivities. A variety of fluoroalkyl halides including ethyl bromodifluoroacetate can be employed. Additionally, an unprecedented decarboxylative fluoroalkylation of α, β-unsaturated carboxylic acids has been achieved via a radical pathway.

A practical sliver-catalyzed fluoroalkylation of aryl-, heteroaryl- and alkylthiols has been developed. The reaction has a good functional-group tolerance and excellent selectivity. A variety of stable and solid fluoroalkanesulfinates including di- and perfluoroalkanesulfinates can be employed. This methodology provides a straightforward and streamlined access to perfluoroalkylthiolated organic molecules. Figure options Download full-size image Download high-quality image (173 K) Download as PowerPoint slide

Regioselective arylthiolations of aromatic amines, arenols and ketones via C–H bond functionalization have been achieved with I2 and PPh3 in an aqueous system, whereby arylsulfenyl radicals are in situ generated from odorless sodium arylsulfinates. The arylsulfenyl radicals can react with free anilines containing electron-withdrawing groups and complex substrates (estrone and progesterone). Further experiments and quantum chemical calculations were also performed to deduce a mechanism for the formation of arylsulfenyl radicals.

A simple and practical method of fluoroalkylthiolation using fluoroalkylsulfonyl chlorides (RfSO2Cl, Rf=CF3, C4F9, C8F17, CF2H and CH2CF3) has been developed. These easy-to-handle reagents are powerful and can be used for electrophilic fluoroalkylthiolation of electron-rich arenes and thiols using diethyl phosphite as reducing agent.

A new strategy for the synthesis of fluorovinyl acetates and β,β-difluoro carboxylates using a hypervalent iodine and hydrogen fluoride-based fluorination reagent is established through a silver-catalyzed one-pot reaction involving formation of carbon-oxygen and carbon-nitrogen bonds. The generated fluoroalkenes substituted with the carbon-oxygen and carbon-nitrogen bond on the β-position have the potential to be transformed into various products which would be difficult to obtain via direct fluorination.

Multicomponent reactions (MCRs) involving three or more components have good pot, atom and step economy. There are dozens of well-known MCRs in literature. Selective examples of newly introduced MCRs, high–order MCRs, MCRs followed by post-condensation modifications, and consecutive MCRs are presented in this chapter.

PASE is a powerful tool in the toolbox of organic synthesis. It has been fully utilized in the design and synthesis of biologically active compounds and natural products. Selective examples of PASE synthesis of these two classes of molecules are presented in this chapter.

The efficiency of organic synthesis is one of the key aspects of green chemistry. Pot, atom, and step economy (PASE) synthesis is an important tool for achieving high synthetic efficiency. Three kinds of PASE methods including one-pot reactions, cascade reactions, and multicomponent reactions are defined in this chapter. Their differences in operation and reaction process are clarified.

One-pot reactions are conducted stepwisely in a single reaction vessel. New contents including reagents, reactants, catalysts, and solvents can be introduced at different steps. The reaction conditions such as temperature and reaction time can also be changed. Presented in this chapter are examples of non-catalytic, catalytic, and cycloaddition reactions conducted in one-pot fashion. This kind of reactions has a good pot economy.

The unprecedented use of CF3SO2Cl for direct bifunctional chloro-trifluoromethylthiolation of alkenes and alkynes is reported. CF3SCl, which is generated by the reduction of PPh3, undergoes electrophilic addition and then chlorination to give the bifunctionalized products without using an additional chlorine source. The method is also applicable for chloro-difluoromethylthiolation using CF2HSO2Cl.

An investigation into the regiochemistry of radical functionalization of indoles using cycloalkanes through di-tert-butyl peroxide (DTBP)-promoted C(sp3)–H activation was conducted. A wide range of indoles bearing substituents at different positions was functionalized directly with simple cycloalkanes in moderate to high regioselectivity. 2-, 4- and 7-positions were mainly functionalized.

A selective and facile trifluoromethylation process for a wide range of thiophenols and thiols under metal free conditions has been developed using two simple and safe solids, sodium trifluoro-methanesulfinate and iodine pentoxide, via the radical process.

A highly efficient dimethylformamide (DMF)-promoted decarboxylative trifluoromethylation of α,β-unsaturated carboxylic acids with Togni (II) reagent under metal-free conditions has been developed. The reactions showed good yields, high stereoselectivities and excellent functional group tolerance. Mechanistic studies confirmed that free-radical processes were involved in this system since the CF3 radical had been clearly trapped by scavengers. This method has been extended to the denitrative trifluoromethylation of β-nitrostyrenes in the presence of an iron(III) catalyst.

A new method for CF3SO2Na-based direct trifluoromethylthiolation of C(sp(2))-H bonds has been developed. CF3SSCF3 is generated in situ from cheap and easy-to-handle CF3SO2Na, and in the presence of CuCl can be used for electrophilic trifluoromethylthiolation of indoles, pyrroles, and enamines. The method has been extended to perfluoroalkylthiolation reactions using RfSO2Na.

A one-pot Michael/aza-Henry/lactamization reaction promoted by recyclable fluorous bifunctional cinchona alkaloid/thiourea organocatalyst has been developed for asymmetric synthesis of fluorine-containing 2-piperidinones bearing four stereogenic centers. The asymmetric Michael adducts induce the formation of other three stereogenic centers to afford products with up to 99% ee and 15 : 1 dr.

A newly developed C–S bond formation process via acid-catalyzed thia-Michael addition has been demonstrated. The protocol, in which Bunte salts generated from odorless and inexpensive sodium thiosulfate and organic halides are used as the thiol precursors, provides an efficient approach for the synthesis of β-sulfido carbonyl compounds.

The highly stereoselective olefination reaction of α-fluoro-β-keto esters for the synthesis of α-fluoro-α,β-unsaturated esters has been developed. The olefination combines nucleophilic addition, intramolecular nucleophilic addition, and elimination in one step, as well as provides a facile synthetic approach to α-fluoro-α,β-unsaturated esters which are important units in many biologically active compounds and useful precursors in a variety of functional-group transformations.

Several derivatives have been synthesized from chrysin, diosmetin, apigenin, and luteolin, which were isolated from diverse natural plants. The α-glucosidase inhibitory activity of these compounds was evaluated. The glucosidase inhibitory activity of all derivatives (IC50

2-Benzimidazolone and their derivatives which have a wide range of biological and pharmaceutical activity are important intermediates for organic synthesis. Reported synthetic methods mostly involved unfriendly materials like phosgene, dimethyl carbonate and urea. This paper developed a novel method for the synthesis of 2-benzimidazolone by the reaction of o-phenylendiamine with triphosgene (BTC) instead of phosgene. BTC is a safer solid and easier to handle compared to phosgene. BTC can greatly reduce risks to both human health and the environment.

In this paper, the heat transfer coefficient and pump consumption power of indirect refrigeration system using CO2 as a secondary refrigerant were investigated experimentally. First, from the comparison of pump consumption powers of existing brines(EG, PG, EA etc.) and CO2 as secondary refrigerants at the same experimental conditions, PG and CO2 show the highest and lowest power, respectively. Second, the heat transfer coefficient of CaCl2 is the highest, but PG is the lowest among other secondary refrigerants. From the above results, it is confirmed that CO2 as the secondary refrigerant has excellent characteristics when comparing to existing brines. Thus, it is concluded that CO2 is applicable as the secondary refrigerant of indirect refrigeration system.