Fluoroalkyl amines

Various sources of fluoride ion have been investigated, of which highly nucleophilic tetraalkylammonium fluorides ate the most effective Thuf, fluoro alkyl halides and N (fluoroalkyl)amines are efficiently synthesized by treatment of the corresponding trifluoromethanesulfonic esters with tetrabutylammonium fluoride trihydrate in aprotic solvents [5fl] (equation 34) The displacement reactions proceed quantitatively at room temperature within seconds, but tail with hydrogen fluoride-pyridine and give reasonable yields only with hydrogen fluo ride-alkylamine reagents... 

Perfluoroalkyl- and perfluoroaryltitanium compounds were prepared m situ via reaction of the corresponding Gngnard reagents with chlorotris(diethyl-amido)titanium [28S] Reaction of the titanium compounds with aldehydes resulted in fluoroalkylative amination [288] (equation 192)... 

There is presently not much evidence for the influence of heteroatoms not directly linked to the inverting nitrogen except for fluoroalkyl amines. The presence of a fluorine atoms, as in N—C—F groups, leads to a decrease in inversion barrier (see 47—50, 53). 

Pirkle,W. H., Hauske, J. R. Design of chiral derivatizing agents for the chromatographic resolution of optical isomers. Asymmetric synthesis of some chiral fluoroalkylated amines, J. Org. Chem.,... 

The reaction proceeds via electrogenerated cationic intermediates as is seen in the anodic oxidation of nonfluorinated amines, carbamates, and amides (Scheme 19). However, the regiochemistry in these processes is not governed by the stability of the cationic intermediates 1 and r because the main products are formed via the less stable intermediates I. Indeed, the promotion effect and unique re-gioselectivity observed in reactions of the fluoroalkyl amines can be explained mainly in terms of the a-CH kinetic acidities of the cation... 

Fluoroalkyl amines [F(CH2) NH2] show alternating toxicity, the even members of the series being much more toxic than the odd. 

Quaternary ammonium salts with fluoroalkyl amines (USP 5,610,128 and USP 5,868,799, Surfactants and Drying and Drydeaning Compositions Which Utilize Said Surfactants)... 

Lewis acids catalyse regio- and diastereo-selective additions of silyl dienolates to fluorinated sulfinylimines, RF-CH=N-S(=0)-Bu allowing access to new chiral a-fluoroalkyl amines. 

A tunable and highly regio- and diastereo-selective addition of acyclic silyl dienolates (6) to several a-fluoroalkyl sulfinylimines (7) has been developed. By appropriate 0 choice of the Lewis acid catalyst, two new chiral a-fluoroalkyl amines (8) and (9) have been obtained in good yields and excellent diastereoselectivities (up to >99 1 dr), respectively (Scheme 3). The high regio- and diastereo-selectivities of different Lewis acid-catalysed reactions have been explained by different transition states. In the case of the TMSOTf-catalysed reaction, the -configuration of the newly formed chiral carbon centre in products (9) could be explained by a non-chelated transition state in which... 

Scheme 2. Use of lithiated sulfoxides in the stereoselective synthesis of p-fluoroalkyl P-amino alcohols and fluoroalkyl amines...

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)... 

Sulfenimines are versatile building blocks for the preparation of secondary and tertiary amines. Therefore, fluoroalkylated sulfenimines should be promising building blocks for the preparation of N-fluoroalkylamino compounds. In fact, very recently, trifluoromethylated sulfenimines have been easily prepared in... 

Fluorination has an important indirect impact on hydrogen bonds, via neighbouring functions (hydroxyl, amine, carbonyl, hydrogen). The electron-withdrawing effect of fluorine atom and of fluoroalkyl groups (CF2, CF3, etc.) deeply modifies the pKg of neighbouring functions, and hence their character of hydrogen bond donors or acceptors (Table 1). 

The synthesis of y-fluoroalkylated allylic alcohols and amines like 51 starting with chiral fluorinated allylic mesylates 50 has also been reported (Eq. 3) [134]. In this case, the regiochemistry of the addition is controlled by the substrate and the addition of the nucleophile occurs distal to the fluorinated alkyl chain. 

When functional groups are present, the products can be quite complex. Primary and secondary amines give NF2 and NF compounds respectively and fluorination of sulphur compounds gives products in which the sulphur has been oxidised to its maximum valency state of six [149] (Table 2.4). Hydroxy compounds can give fluoroalkyl hypo-fluorites (fluoroxy compounds) (see also Chapter 3, Section IIIB), the corresponding alkyl derivatives not being stable [150, 151] bisfluoroxy derivatives have also been isolated [152-154] (Figure 2.27). 

Fluoroalkyl groups correspondingly lower the strengths of bases. Table 4.3 shows the dissociation constants of some amines, together with hydrocarbon derivatives for comparison. 

---