The Trifluoroethylamine Function as Peptide Bond Replacement

Trifluoromethylation of the amide group

“…The yield of compound 2 was 311 mg (80%), a light yellow oil, R f 0.20 (hexane-EtOAc, 6 : 1). 1 1 Benzyl 2 trifluoromethylpyrrolidine (3). Sodium boro hydride (29 mg, 0.75 mmol) and BF 3 •OEt 2 (71 μL, 0.56 mmol) were successively added to a solution of α methoxy amine 2 (130 mg, 0.5 mmol) in dioxane (1 mL).…”

“…It should be emphasized that compound 4c contains adjacent quaternary C atoms, which is evidence for the efficiency of this method of C-C bond formation. 1 H, 13 C, and 19 F NMR spectra were recorded on Bruker AM 300 and Bruker AC 200 instruments in CDCl 3 . Dichloro ethane and dichloromethane were distilled over CaH 2 immedi ately before use; DMF was distilled in vacuo over P 2 O 5 and kept over molecular sieves (4 Å).…”

Synthesis of CF3-substituted 1,2,3,4-tetrahydroisoquinolines and 1,2,3,6-tetrahydropyridines

“…Combined extracts were concentrated in vacuo.1,2 Dimethyl 1,2 dihydroisoquinoline (2c). The residue was distilled in vacuo to obtain colorless oil, 53% 1. H NMR (300 MHz, CDCl 3 ), δ: 2.78 (s, 3 H, NMe); 4.20 (s, 2 H, CH 2 ); 5.33 (d, 1 H, NCHCH, J = 7.3 Hz); 6.10 (d, 1 H, NCH, J = 7.3 Hz); 6.84-7.20 (m, 4 H, Ar).…”

“…1 H NMR (300 MHz, CDCl 3 ), δ: 0.91 (d, 3 H, CHMe A Me B , J = 6.8 Hz); 1.00 (d, 3 H, CHMe A Me B , J = 6.8 Hz); 2.00-2.21 (m, 1 H, CHMe 2 ); 3.09 (s, 3 H, NMe); 4.08 (d, 1 H, Pr i CH, J = 6.8 Hz); 5.23 (d, 1 H, NCHCH, J = 6.8 Hz); 6.16 (d, 1 H, NCH, J = 6.8 Hz); 6.81-6.96 (m, 2 H, Ar); 6.96-7.20 (m, 2 H, Ar).2 Methyl 1 phenyl 1,2 dihydroisoquinoline (2d). The resi due was recrystallized from hexane to obtain light brown crys tals, 87% 1. H NMR (300 MHz, CDCl 3 ), δ: 2.75 (s, 3 H, NMe); 5.27 (d, 1 H, NCHCH, J = 7.3 Hz); 5.42 (s, 1 H, PhCH); 6.22 (d, 1 H, NCHCH, J = 7.3 Hz); 6.77 (d, 1 H, Ar, J = 8.0 Hz); 6.86-7.00 (m, 2 H, Ar); 7.02-7.18 (m, 1 H, Ar); 7.24-7.50 (m, 5 H, Ar).Reaction of isoquinolinium salts with lithium triethylboro hydride (general procedure).…”

“…[1][2][3][4] The most efficient approaches to α CF 3 sub stituted amines include nucleophilic addition 5 and 1,3 proton shift 6 reactions involving imines of trifluoro acetic aldehyde, as well as addition reactions of trifluoro methyl carbanion at the C=N bond of azomethine sub strates 7, 8 and iminium cations. 9 Among different α (trifluoromethyl)amines, 3 tri fluoromethyl 1,2,3,4 tetrahydroisoquinolines are of spe cial interest, 4 since they are selective inhibitors of phenyl ethanolamine N methyltransferase, the enzyme catalyzing the last step of biosynthesis of adrenalin.…”