Trifluoromethylated amino

W-(Methoxycarbonyl)triphenylphosphine imide reacts with methyl trifluoro-pyruvate to form methyl A -methoxycarbonyl 2 immo-3,3,3 trifluoropropionate m 95% yield This convenient building block easily adds nucleophiles such as Gngnard reagents without competing side reactions at the ester group to form trifluoromethylated amino acids [J.S] (equation 31)... 

N,N-Bis(trifTuoromethyl)propadienylamine or l,3-his[N,N-bis(trifluoromethyl)]-aminopropadiene reacted with di(trifluoromethyl)amino bromide to give the center-attack products 264—266 [134],... 

Preparation of a-Trifluoromethyl Amino Acids Since trifluoro-... 

Another powerful approach to prepare a-amino acids bearing an aromatic or unsaturated side chain in /I (but also many other compounds) is based on the reactivity of 5-fluoro-4-trifluoromethyloxazole, a starting material easily accessible from hexafluoroacetone. The fluorine atom in the 5 position is easily displaced by an allylic or benzylic alcohol. Then, the obtained ethers spontaneously undergo a Claisen rearrangement to afford, after acidic hydrolysis, an a-trifluoromethyl amino acid... 

Figure 5.31). Functional modification of the double bond leads to numerous analogues of proteogenic or nonproteogenic a-trifluoromethyl amino acids. 

Numerous peptides have been prepared starting from trifluoromethylalanine. 31, 120 Cyclopeptides containing a-trifluoromethyl amino acids have also be prepared. Some peptidic coupling performed with other a-trifluoromethyl amino acids involve protease catalysis (subtilisin, a-chymotrypsin, carboxypeptidase Y, trypsin, etc.). ... 

Replacement of some amino acids in a peptide by an a-trifluoromethyl amino acid influences the stability of the peptide toward different proteases (e.g., a-chymotrip-sins). Thus, for steric reasons, introducing a trifluoromethyl group in the P] position... 

Figure5.31 Synthesis of a-trifluoromethyl amino acids starting from trifluoromethyl fluorooxazole by Claisen rearrangement. ...

Though not available commercially, trifluoronitroethane shows some interesting chemistry consistent with the powerful electron-withdrawing effect exerted by the nitro group. Fluoride-mediated nitroaldol reactions were reported [144] with aldehydes affording a valuable entry to trifluoromethyl amino alcohols... 

The oxidative desulfurization-fluorination of methyl A,-alkyl-A,-pyridyl(or pyrimidin-yl)dilhiocarbamates produces the corresponding (trifluoromethyl)amino-substituted pyridines (or pyrimidines) 5.69... 

Bis 4-chlorophenyl(trifluoromethyl)amino Sulfide (Ic) Typical Procedure 137... 

Sulfur tetrafluoride undergoes oxidative incorporation into a number of compounds of high oxidation state to form six-coordinated sulfur fluorides. Thus, reaction with bis(trifluorometh-yl)nitrogen oxide proceeds at ambient temperature and gives bis [bis(trifluoromethyl)amino]-oxy sulfur tetrafluoride (9) almost quantitatively.214... 

T rifluoromethyl-phenyl-amino)-nicotinic acid, 2-[[3-(trifluoromethyl)]amino]-3-pyrodinecarboxylic acid, Ci3H9F3N202, Mr 282.22, mp 204 °C... 

Bis(trifluoromethyl)nitroxyl readily attacks the C = C bond of fluoroalkenes. Two radicals add across the C = C bond95-97 to give the corresponding vicinal bis[bis(trifluoromethyl)amino-oxy]alkanes 60 in 80% to quantitative yields. Even fluoroaromatic compounds react in the same way (vide infra). 

Bis(trifluoromethyl) nitroxide abstracts aldehydic hydrogen atoms from perfluorobenzaldehyde with great case, to give the ( [bis(trifluoromethyl)amino]oxyjcarbonyl)arene in almost quantitative yields.188 The reaction has also been extended to other classes of compounds (vide infra).189... 

Dehydrobromination of 2-bromo-A, A -[bis(trifluoromethyl)]-prop-2-en-l-amine (25) gives allene 26 and propyne 27-"7 In these reactions, the bis(trifluoromethyl)amino group survives. 

Ethine Bix-[bis-(trifluoromethyl)-amino]- ElOb,. I()3( — HBr- In) Hydrazine, Bis-[hcxatluoro-isopropy-lidenc]- ElOb,. 551 f. (Educt)... 

Sulfane Bis-[(2-phenyl-ethyl)-trifluoromethyl-amino]- ElOa. 258 (RN = CS + IF5)... 

Mercury bis[pentafluorotelluro(trifluoromethyl)amide] reacted with elemental halogens and interhalogens to yield ha]o(trifluoromethyl)amino tellurium pentafluoride2,3. The less electronegative halogens of the interhalogens join the amide-nitrogen atom. 

N- a-Chloro- a- [bis(trifluoromethyl)amino]methylene -N- a, a-dichloro-a-[bis-(trifluoromethyl)amino]methyl amine (293) gave 2,3,5,6-tetraks[bis(trifluo-romethyl)amino] pyrazine (294) (Ph3P, 120°C, 6 h 6% as a distillate/subli-mate a mechanism was suggested).1321... 

A mixture of Lil (2.23 g. 16.7 mmol) and [bis(trifluoromethyl)amino]aeetyl fluoride) (4.15 g, 13.9 mmol) was heated at 180 C for 6.5 hina Fyrex tube (13 mm x 180 mm). The iodides were separated by trap-to-trap distillation using consecutive traps cooled at - 78 and 196 C. The compounds retained in the — 78 C trap (5.59 g) consisted mainly of iodides and small quantities of unreacted substrate. The crude iodide, liale-purple colored, was further purified by preparative GC yield 3.21 g (61 %). 

---