Fluoroalkylated synthesis

Pyrimidine, 2-ethyl-1,4,5,6-tetrahydro-synthesis, 3, 108 Pyrimidine, 5-formyl-2-methyl-in thiamin biosynthesis, 1, 99 Pyrimidine, fluoro-syhthesis, 3, 140 Pyrimidine, 2-fluoro-NMR, 3, 63 synthesis, 3, 140 Pyriihidine, 4-fluoro-synthesis, 3, 140 Pyrimidine, 6-fluoro-synthesis, 3, 140 Pyrimidine, fluoroalkyl-synthesis, 3, 77... 

The synthesis of fluoroalkyl and chloroalkyl fluoromethyl ketones is achieved by oxidation of the corresponding alcohols by sodium dichromate and sulfunc acid in methylene chlonde in the presence of a phase transfer catalyst [49] (equation 45)... 

Fluorinated sulflnates are prepared from sodium dithionite and liquid per-fluoroalkyl halides [74] (equation 67). For the transformation of the gaseous and poorly reactive trifluoromethyl bromide, it is necessary to use moderate pressure [75] (equation 68) These reactions are interpreted by a SET between the intermediate sulfur dioxide radical anion and the halide The sodium trifluorometh-anesulfinate thus obtained is an intermediate for a chemical synthesis of triflic acid. 

Selectivity and reactivity of mixed anhydrides toward primary and secondary aliphatic and aromatic amines has been studied in details [42, 43] (equation 22) Fluorocarboxyhc acids and then denvahves are used as building blocks m condensa non reactions widi dmucleophihc species for the synthesis of fluoroalkyl-subshtuted lieteroaromahc systems [S 9, 40, 44, 45, 46, 47 4S] (equations 20 21, and 23)... 

Polyfunctional fluoroalkyl-containing carbonyl compounds in the synthesis of heterocycles 98IZV1279. 

The metathesis reaction of fluorinated alkyl iodides with reagents such as CdMe2 is a well-established procedure for the synthesis of fluoroalkyl cadmium derivatives. A recent application of this method has allowed for the synthesis of compound 186, as shown in Scheme 22.248 This reaction is accompanied by formation of 187, which results from the insertion of the difluorocarbene in the methyl-cadmium bond. Presumably, the difluorocarbene is generated by a radicalar process involving HCF2I and CdMe2. 

Jean-Pierre Begue, Daniele Bonnet-Delpon, and Andrei Kornilov 153 WITTIG OLEFINATION OF PER-FLUOROALKYL CARBOXYLIC ESTERS SYNTHESIS OF 1,1,1-TRIFLUORO-2-ETHOXY-5-PHENYLPENT-2-ENE AND 1 -PERFLUOROALKYL EPOXY ETHERS 1,1,1-TRIFLUORO-2-ETHOXY-2,3-EPOXY-5-PHENYLPENTANE... 

A 50% functionalization evokes the interesting question, bearing in mind facile transesterification, of how the fluoroalkyl chains will be distributed over the molecules and how they will be distributed on one particular molecule This question has been examined in detail for dendrimers of the poly(propyleneimine) type functionalized with stearic acid [33]. It was proven that the compositional heterogeneity (distribution of degree of substitution) is random, but the positional heterogeneity (spatial distribution of the substituents over the dendrimer molecule) is not random. However, due to flexibility, no particular effect of the spatial distribution can be observed. Unlike the dendrimers, we expect the hyperbranched polyesteramides to be stiffer, so that spatial distribution could lead to interesting effects if the molecule were composed of a functionalized side and a non-func-tionalized side (Fig. 28), as shown possible for dendrimers via a convergent synthesis [34]. 

One of the earliest uses for rhodium(II)-catalyzed dipoles was demonstrated in Davies furan synthesis [22]. Isomiinchnones were also shown to produce substituted furans [115]. Additional furan syntheses have been described using silylacetates [116], unsaturated esters [117], and fluoroalkyl diazo acetates [118]. The synthesis of furofuranones and indenofuranones 35 from a-diazo ketones having pendant alkynes has also been reported (Eq. 6) [119]. Other fused heterocyclic systems include furo[3,4-c]furans [120, 121] furo[2,3-b]furans [122] as well as thiobenzofurans [123], and benzoxazoles[124] have also been synthesized with this methodology. 

Putilova ES, Troitskii NA, Zlotin SG, Khudina OG, Burgart YV, Saloutin VI, Chupakhin ON (2006) One-step solvent-free synthesis of fluoroalkyl-substituted 4-hydroxy-2-oxo(thioxo) hexahydropyrimidines in the presence of l-butyl-3-methylimidazolium tetrafluoroborate. Russ J Org Chem 42 1392-1395... 

Utilization of UNs with fluoroalkyl substituents 201 makes possible the synthesis of 4,4-disubstituted fluorine-containing pyrans 202 (02JFC63) (Scheme 75). Phospho- and fluoro-containing pyranopyrazoles 203 were obtained similarly (04JFC1853) (Scheme 75). 

Fluoroalkyl copper compounds, 17 143, 144 a-Fluoroalkylidinehydrazines, 33 167 2-Fluoroalky 1 -2 phospha-1,3-dialky 1 -1,3-diaze-tidinones, synthesis of, 14 87 Fluoroanions, trivalent, uranium, 34 94—95 Fluoroantimony compounds, 7 17 Huoroaryl copper compounds, 17 143, 144 Fluoroberyllates anhydrous, 14 267-276 aqueous chemistry of, 14 274-278 glasses, 14 265-267 preparation and properties of, 14 265-267... 

N. Truong Thi Thanh, C. Menage, J.P. Begue, D. Bonnet-Delpon, J.C. Gantier, B. Pradines, J.C. Doury, T. Truong Dinh, Synthesis and antimalarial activities of fluoroalkyl derivatives of dihydroartemisinin, J. Med. Chem. 41 (1998) 4101-4108. 

The a-elimination process is a very fast and effective reaction of trifluoromethyl carbanions (Figure 1.9)." Consequently, the corresponding organometallic species (Li, Mg) cannot be used in organic synthesis. When the carbon-metal bond is close to a covalent bond, the anionic species is more stable, but has almost no reactivity toward electrophiles. Zinc, and especially silicon, derivatives constitute the best compromises." When the fluoroalkyl chain is longer, organometallics are more stable and can be used in synthesis (Figure 1.10)." ... 

After a decrease in the importance of steroids in the field of drug research during the last 20 years, a renewal is now being observed. Recently, some fluorinated and fluoroalkylated steroids have been launched or are in advanced phases of clinical development, such as the dutasteride (5a-reductase inhibitor), CCD-3693 (GABA agonist), fulvestrant and antiprogestine (antihormone), and fluasterone (diabetes) (Figure 4.14). Details on the synthesis on these compounds can be found in Chapter 8. 

The oldest methods for synthesis involve the condensation-cyclization of trifluor-omethyl or fluoroalkyl pyrroles in the presence of a metal salt. These reactions afford tetrakis(fluoroalkyl) porphyrins. The electrophilic trifluoromethylation of porphyrins is selective and leads to /I-CF3 and meso-CVT, porphyrins. While condensation of meio-trifluoromethyl-dipyrromethane with an aldehyde in acidic medium is rather difficult, it proceeds with better yields and permits a selective introduction of trifluoromethyl groups in meso The Ruppert reagent (CF3TMS) has been used to... 

Racemic jS-fluoroalkyl tyrosines and phenylalanines have been prepared by classical methods starting from the corresponding fluoroacetophenones. Synthesis of the nonracemic compounds is much more difficult, as exemplified by the preparation of jS-difluoromethyl meta-tyrosines (Figure 5.14). jS-Trifluoromethyl tryptophan is prepared by alkylation of ethyl acetamido malonate with indolyl-2,2-trifluoroethanol. Surprisingly, the decarboxylation reaction leads stereoselectively to the syn isomer (Figure 5.15). ... 

Generally, the a-fluoroalkyl amino acids cannot be prepared by means of classical methods. Thus, original methods for their synthesis have been required and set up. ... 

Fluoroalcohol ethers, such as —O—CH2—Rf, or ketals of fluoroalkyl ketones. Their synthesis has been described only recently. 

Perfluoro(3-isothiocyanato-2-methyl-2-pentene) reacts with N-nucleophiles to produce a series of fluoroalkyl-substituted 6/f-l,3-thiazines <1997RJO720>. The acid-catalyzed cyclization of thioureas immobilized on Wang (X = O) or Rink resin (X = NH) provides a convenient route to a wide range of 2-amino-4/7-benzothiazine derivatives 212 (Scheme 23) <20000L3667>. The thioureas are obtained in four steps from 2-nitrocinnamic acids. A general synthesis of 2-alkylidene-4-imino-l,4-dihydrobenzo-l,3-thiazines 213-215 involves treatment of 2-isothiocyanato-benzonitrile with acidic methylene compounds under basic conditions <2003SL1503>. The ( )-isomers are the predominant isomers formed. 

---