Simple and highly diastereoselective synthesis of trifluoromethyl-containing myosmines via reaction between 2-(aminomethyl)pyridine and 1,1,1,5,5,5-hexafluoro-2,4-pentanedione

Tetrahedron Letters

Volumn 44, Issue 11, 2003, Pages 2417-2420

  Ohkura, Hironari ^a   Berbasov, Dmitrii O ^a   Soloshonok, Vadim A ^a  

^a UNIVERSITY OF OKLAHOMA   (United States)

Author keywords

1,3 proton shift; Epimerization; Fluorine containing compounds; Kinetic thermodynamic diastereoselectivity

Indexed keywords

1,1,1,5,5,5 HEXAFLUORO 2,4 PENTANEDIONE; 2 (AMINOMETHYL)PYRIDINE; ACETYLACETONE; CARBOXYLIC ACID DERIVATIVE; PYRIDINE DERIVATIVE; PYRROLINE DERIVATIVE; TRIETHYLAMINE; UNCLASSIFIED DRUG;

ARTICLE; CYCLIZATION; DIASTEREOISOMER; DRUG SYNTHESIS; EPIMERIZATION; KINETICS; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; STEREOCHEMISTRY; THERMODYNAMICS;

EID: 0037430440     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(03)00244-2     Document Type: Article

References (30)

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21. Standard reaction conditions for preparing imines from carbonyl compounds and primary amines were used: reflux of the starting compounds in toluene in the presence of catalytic amounts of p-toluenesulfonic acid and trapping the releasing water with a Dean-Stark device.
22. 19F NMR) in the reaction mixture.
23. 2O: C, 44.31; H, 2.70; F, 38.23; N, 9.39. Found: C, 44.31; H, 2.69; F, 38.24; N, 9.38.
24. General procedure for preparing 3-hydroxyl-3,5-ditrifluoromethyl-myosmine 4 and 5: To a solution of 2-(aminomethyl)pyridine (2.859 g, 26.435 mmol) in 10 mL of toluene benzoic acid (3.228 g, 26.435 mmol) were added at rt. The resultant suspension was stirred for 5 min followed by an addition of 1,1,1,5,5,5-hexafluoro-2,4-pentanedione (4.996 g, 24.032 mmol) in 10 mL of toluene. The mixture was heated at 140°C for 1 h, cooled down and treated with triethylamine (20 mL) to neutralize the benzoic acid. The mixture was evaporated in vacuum and the products were isolated by column chromatography (hexanes/AcOEt 10/1, v/v).
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26. 3CN (6 mL) was added triethylamine (0.58 mL, 4.00 mmol) and the resultant mixture was kept at 75°C for 24 h. The solvent and triethylamine were removed under reduced pressure and the residue was subjected to column chromatography (hexanes/AcOEt 10/1, v/v) to afford 0.2241 g (94%) of product 5.
27. TSs 9 and 10 were drawn only for trans-conformers of 8 and 9 (relative position of the nitrogens). Similar structures could be drawn for the corresponding cis-conformers without influencing the discussed stereochemical outcome.
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30. The pyridine moiety in compounds 4 and 5 is basic enough to assist the epimerization.