Synthesis of hindered tertiary amines by a mild reductive amination procedure

Tetrahedron Letters

Volumn 48, Issue 3, 2007, Pages 365-369

  Menche, Dirk ^a   Böhm, Stefanie ^a   Li, Jun ^a   Rudolph, Sven ^a   Zander, Wiebke ^a  

^a HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

Author keywords

Hantzsch ester; Organocatalysis; Reductive amination; Synthetic methodology; Tertiary amines

Indexed keywords

CARBONYL DERIVATIVE; HANTZSCH ESTER; IMINE; REAGENT; TERTIARY AMINE; THIOUREA;

AMINATION; ARTICLE; CATALYSIS; CHEMICAL STRUCTURE; HYDROGENATION; REDUCTION; STEREOCHEMISTRY; SYNTHESIS;

EID: 33845428157     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2006.11.082     Document Type: Article

References (25)

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20. General procedure: A solution of the amine (3a-b, 1.00 mmol) and the carbonyl component (4a-d, 2.20 mmol) in toluene (5 mL) was treated with the Hantzsch ester (3, 760 mg, 2.40 mmol), thiourea (4, 7.6 mg, 0.100 mmol) and MS 5 Å (1.0 g) and the mixture was stirred under nitrogen at 60 °C until complete conversion (24-72 h). After filtration over Celite, the solvent is evaporated and the residue purified by flash chromatography on silica gel using mixtures of petroleum ether and ethyl acetate as eluants to give the product amines (7a-f) in a pure form.
21. The use of only 2 equiv of the carbonyl component leads to a decrease in the isolated yields, in particular when volatile aldehydes are used.
22. The second amination step is much slower due to steric reasons, which allows a selective amination for the synthesis of secondary amines, as previously reported: see Ref. 5. For optimum conversion also in the second amination step, thiourea is crucial.
23. +: 314.1630. Found: 314.1634.
24. For the synthesis of the secondary amines, see Ref. 5.
25. General procedure: A solution of the secondary amine (8a-e, 1 mmol) and the aldehyde (4a/b/e 1.2 mmol) in toluene (5 mL) was treated under nitrogen with the Hantzsch ester (3, 390 mg, 1.50 mmol), thiourea (4, 7.6 mg, 0.100 mmol) and MS 5 Å (1.0 g) and the mixture was stirred at 60 °C until completion of the reaction (24-72 h). After filtration over Celite, the solvent is evaporated and the residue purified by flash chromatography on silica gel using mixtures of petroleum ether and ethyl acetate as eluents to give product amines (9a-h) in a pure form.