RESUMO
α-Trifluoromethyl azocanes are accessible from 2-(trifluoropropan-2-ol) piperidines by metal-free ring-expansion involving a bicyclic azetidinium intermediate. The opening of the azetidinium intermediate was achieved by various nucleophiles (amines, alcoholates, carboxylates, phosphonates, halides and pseudo-halides) with an excellent regio- diastereo- and enantioselectivity and in good yields. The relative configuration of the piperidines and azocanes were assigned and the deprotected azocanes offer opportunities for further derivatization.
Assuntos
Aminas , PiperidinasRESUMO
A comprehensive survey of pathways leading to the generation of α-trifluoromethyl monocyclic piperidinic derivatives is provided (65 references). These compounds have been synthesized either from 6-membered rings e.g., pipecolic acid or lactam derivatives by introduction a trifluoromethyl group, from pyridine or pyridinone derivatives by reduction, and from 5-membered rings e.g., prolinol derivatives by ring expansion, from linear amines by cyclization or from dienes/dienophiles by [4 + 2]-cycloaddition.
Assuntos
Aminas/química , Piperidinas/síntese química , Ciclização , Reação de Cicloadição , Estrutura Molecular , Piperidinas/química , Pirrolidinas/química , EstereoisomerismoRESUMO
The enantioselective syntheses of 3-amino-5-fluoropiperidines and 3-amino-5,5-difluoropiperidines were developed using the ring enlargement of prolinols to access libraries of 3-amino- and 3-amidofluoropiperidines. The study of the physicochemical properties revealed that fluorine atom(s) decrease(s) the pKa and modulate(s) the lipophilicity of 3-aminopiperidines. The relative stereochemistry of the fluorine atoms with the amino groups at C3 on the piperidine core has a small effect on the pKa due to conformationnal modifications induced by fluorine atom(s). In the protonated forms, the C-F bond is in an axial position due to a dipole-dipole interaction between the N-H(+) and C-F bonds. Predictions of the physicochemical properties using common software appeared to be limited to determine correct values of pKa and/or differences of pKa between cis- and trans-3-amino-5-fluoropiperidines.
Assuntos
Técnicas de Química Combinatória , Hidrocarbonetos Fluorados/síntese química , Piperidinas/síntese química , Hidrocarbonetos Fluorados/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Piperidinas/química , EstereoisomerismoRESUMO
The monoalkylation of acetonitrile by primary alcohols was achieved in a one-pot sequence in the presence of iridium catalysts. A diversity of nitriles has been obtained from aryl- and alkyl-methanols in excellent yield.
Assuntos
Acetonitrilas/química , Álcoois/química , Irídio/química , Alquilação , Catálise , Estrutura MolecularRESUMO
The activation of N-alkyl prolinols by XtalFluor E allowed the formation of an aziridinium intermediate that can react with tetrabutylammonium azide (nBu(4)NN(3)) to produce 3-azidopiperidines and/or 2-(azidomethyl)pyrrolidines, in a ratio up to 100/0. These 3-azidopiperidines can be reduced to the corresponding 3-aminopiperidines.
Assuntos
Aminas/química , Azidas/química , Piperidinas/química , Pirrolidinas/química , Estrutura Molecular , Compostos Organometálicos , Oxirredução , EstereoisomerismoRESUMO
An organo-catalyzed Henry reaction, applied to an alpha-keto ester, has allowed the enantioselective synthesis of SSR 241586, a 2,2-disubstituted morpholine active in the treatment of schizophrenia and irritable bowel syndrome (IBS).
Assuntos
Síndrome do Intestino Irritável/tratamento farmacológico , Morfolinas/síntese química , Morfolinas/farmacologia , Catálise , Ésteres , Morfolinas/química , EstereoisomerismoRESUMO
Beta-amino alcohols derived from natural amino acids have been used extensively as a powerful source of chirality. Transformation of the hydroxy group of these beta-amino alcohols into a good leaving group, by using trifluoroacetic anhydride, led to rearranged beta-amino alcohols in good yields and with high enantiomeric excesses. This rearrangement has allowed the transformation of substituted prolinols to substituted 3-hydroxypiperidines and linear beta-amino alcohols, issued from natural amino acids, to rearranged beta-amino alcohols.
Assuntos
Amino Álcoois/química , Preparações Farmacêuticas/síntese química , Amino Álcoois/síntese química , Catálise , Preparações Farmacêuticas/química , EstereoisomerismoRESUMO
Carrots (Daucus carota) were used to reduce cyclic amino-ketones in high yields and enantiomeric excesses. This cheap, eco-compatible, and efficient reducing reagent allows the easy access to precursors of biologically active products.
Assuntos
Aminas/química , Daucus carota/metabolismo , Cetonas/química , Piperidinas/química , Pirazóis/síntese química , Estrutura Molecular , Oxirredução , Piperidinas/síntese química , Pirazóis/química , EstereoisomerismoRESUMO
The formal total synthesis of (S,S)-reboxetine has been realized by two different approaches using a stereospecific rearrangement of beta-amino alcohols catalyzed by (CF3CO)2O.
Assuntos
Amino Álcoois/química , Morfolinas/síntese química , Catálise , Conformação Molecular , Morfolinas/química , Reboxetina , EstereoisomerismoRESUMO
Highly enantioselective rearrangement of beta-amino alcohols was realized by using a catalytic amount of trifluoroacetic anhydride.
Assuntos
Amino Álcoois/síntese química , Amino Álcoois/química , Catálise , Espectroscopia de Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , EstereoisomerismoRESUMO
[reaction: see text] N,N-Dialkyl-beta-amino alcohols derived from alpha-amino acids can be rearranged enantiospecifically by using TFAA/Et3N/NaOH to give 1,2-amino alcohols with enantiomeric excess up to 99%.
Assuntos
Aminoácidos/química , Amino Álcoois/síntese química , Amino Álcoois/química , Técnicas de Química Combinatória , Estrutura Molecular , EstereoisomerismoRESUMO
[reaction: see text] The alpha-arylation of the zinc enolate of N-protected 2-piperidinones with aryl bromides in the presence of a palladium catalyst is described as a general method.