Selective introduction of fluorine into

The selective introduction of fluorine into a furanose ring was demonstrated by the reaction of TASF with l,2 5,6-di-0-isopropylidene-3-O-trifluoromethanesulfonyl-a-D-allofuranose (12) which gave a 66% yield of 3-deoxy-3-fluoro-l,2 5,6-di-0-isopropylldene-a-D-glucofuranose (2. The isomeric triflate 13,... 

Some interesting aspects of the mechanism of the selective introduction of fluorine into sulfur-containing compounds arc discussed52 below. A sulfonium ion can be obtained by the oxidation of sulfides. 

Selective introduction of fluorine into an aromatic ring is often achieved by thermal decomposition of diazonium fluoroborates, which is called the Balz-Schiemann reaction (Scheme The scope of... 

Therefore, starting in the 1980s, medicinal chemists discovered that the selective introduction of fluorine into biologically active molecules exercised an influence on activity there are numerous reports of compounds incorporating fluorine as either a bioisosteric replacement for hydrogen or an isoelectronic replacement for the hydroxyl group [ 1,2],... 

Selective introduction of fluorine into an aromatic ring is often achieved by thermal decomposition of diazonium fluoroborates, which is called the Balz-Schiemann reaction (Scheme 37). 25 i26 jjie scope of the reaction is wide and includes heterocyclic compounds (equation 47). The Bp4 salts are unusually stable for diazonium salts and yields are usually high. In some cases, however, use of Pp6 or Sbp6 salts gives improved yields. ... 

Electrophilic fluorination is one of the most direct methods for selective introduction of fluorine into organic compounds. Historically first electrophilic fluorination of diazine derivatives was accomphshed in 1960. Silver difluoride has been used in the final stage of an earlier synthesis of tetrafluoropyrimidine 6 from trifluoropyrimidine 5 [14]. Later the similar transformation was carried out using CIF5 in 15 % yield and was found that side chlorination occurs in 9 % yield [15] (Scheme 1). 

This chapter will deal mainly with the chemistry of highly fluorinated compounds, although this will be prefaced by a more general summary of synthetic methods for the introduction of fluorine into an aromatic system. A review of this topic by Brooke [1] covers the area in considerable detail and we can only be selective in our discussion here. 

The development of synthetic methods for the selective introduction of short-chain perfluoroalkyl groups into organic molecules is of interest in drug development [464]. Fluoromodifications often confer unique properties on a molecule, for example in terms of increased metabolic stability and lipophilicity and, as a consequence, the pharmacokinetic profiles are often improved [465]. Burger and coworkers developed a domino process consisting of a SN reaction combined with a Claisen and a Cope rearrangement which allows the transformation of simple fluorinated compounds into more complex molecules with fluoro atoms [466]. Treatment of furan 2-917 with 2-hydroxymethyl thiophene (2-918) in the presence... 

Due to the unique properties of fluorinated compounds there has been a growing interest in the selective introduction of one or more fluorine atoms into organic molecules (Shimizu and Hiyama 2005 Welch and Eswarakrishnan 1991 Soloshonok 1999 Chambers 2004). In particular, the resistance to many metabolic transformations, as well as the increased lipophilicity and stability of fluorine-containing compounds is of importance to the pharmaceutical and agrochemical industry... 

Akiyama, Y., Hiramatsu, C., Fukuhara, T., and Kara, S. 2006. Selective introduction of a fluorine atom into carbohydrates and a nucleoside by ring-opening fluorination reaction of epoxides. Journal of Fluorine Chemistry, 127 920-23. 

The [4+1] cycloadducts formed from 4,4-bis(trifluoromethyl)-l-oxa-buta-1,3-dienes (92JPR219) and tin(II )-chloride are transformed on heating into 4,4-difluoro-3-trifluoromethylbut-3-en-l-ones, which on treatment with sodium hydride yield 2-fluoro-3-trifluoromethylfurans (92CC348). When heated with phosphorus pentasulfide, l-aryl-4,4-difluoro-3-trifluor-omethylbut-3-en-l-ones give 2-fluoro-3-trifluoromethylthiophenes. The fluorine atom at C—2 of the furans and thiophenes can readily be substituted by a wide variety of nucleophiles (92JPR3II). This reaction sequence represents a preparatively useful method for the selective introduction of biologically relevant substituents into the C—2 position of 3-trifluoro-methyl-substituted furans and thiophenes (Scheme 87). 

Selective introduction of a fluorine atom into organic compounds is important due to the unique biological and physical properties of fluorinated compounds. One useful method for C-F bond formation is desulfurative fluorina-tion realized by a cleavage of C-S bonds of dithioacetals. Thus, 1,3-ditholane derivatives undergo a facile reaction... 

Since the 1950s perfluoroahphatic SF5 compounds have been made by a variety of methods, including fluorination with cobalt trifluoride and direct and electrochemical fluorination [42a]. Selective introduction of a pentafluorosulfuranyl group into more complex aliphatic compounds, on the other hand, remains still a challenge. 

The increasing importance of fluoroaromatics as fine chemicals and continuing research into more selective or directed fluorination methods suggests that the future may see the introduction of more industrial processes, especially for those compounds such as the 1,2-difluorobenzenes which are difficult or expensive to produce by existing technologies. 

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