RESUMO
The regioselective and enantioselective Michael addition between azlactones and o-hydroxy chalcone derivatives is reported. Enantiomerically enriched N,O-aminals with two continuous stereogenic centers are exclusively obtained in moderate to good yields with excellent diastereoselectivities and good to excellent enantioselectivities. The experimental results show that an o-hydroxy group on the cinnamenyl motif of chalcone derivatives plays a crucial role at the reaction sites for the regioselective Michael addition. In addition, circular dichroism (CD) spectroscopy and density functional theory (DFT) are used to investigate the absolute configuration of N,O-aminals and the corresponding transition-state structures.
Assuntos
Acetais/química , Aminas/química , Compostos Aza/química , Chalcona/química , Lactonas/química , Catálise , Dicroísmo Circular , Modelos Moleculares , Estrutura Molecular , Nitrogênio/química , Oxigênio/química , EstereoisomerismoRESUMO
The tandem oxo-Michael-IED/HDA and oxo-Michael-IED/HDA-Michael-Aldol condensation transformations between (E)-2-hydroxyaryl-2-oxobut-3-enoate derivatives with enals have been developed in the presence of (S)-diphenylprolinol trimethylsilyl ether as an organocatalyst. Two types of tricyclic chroman derivatives were, respectively, obtained, by adjusting the reactant ratio and reaction temperature, in good yields (up to 96%) with excellent enantioselectivities (up to >99%) and good diastereoselectivities (up to >30/1). It should be noted that the divergent chiral chroman derivatives were obtained by successive reaction of (E)-2-hydroxyaryl-2-oxobut-3-enoate derivatives with two different enal substrates in highly catalytic results.
Assuntos
Butiratos/química , Cromanos/síntese química , Éteres/química , Pirrolidinas/química , Compostos de Trimetilsilil/química , Catálise , Cromanos/química , Estrutura Molecular , EstereoisomerismoRESUMO
A diastereo- and enantio-selective domino Michael-cyclization-tautomerization reaction of isatylidene malononitriles with α,α-dicyanoalkenes catalyzed by a cinchona alkaloid-derived bifunctional thiourea catalyst has been developed. A series of multi-functionalized spiro oxindole diene derivatives have been obtained in good to excellent yields (up to 97%) with good to excellent enantioselectivities (up to 96%) as well as good diastereoselectivities (up to 7.9 : 1). In addition, an anomalous temperature effect on the enantioselectivity has also been studied for this transformation.
Assuntos
Indóis/síntese química , Compostos de Espiro/síntese química , Catálise , Cromatografia Líquida de Alta Pressão , Cristalografia por Raios X , Indóis/química , Conformação Molecular , Oxindóis , Compostos de Espiro/química , Estereoisomerismo , TemperaturaRESUMO
Because of the importance of the indole framework and the versatile transformation of nitro and formyl groups, the efficient synthesis of optically pure 2-alkyl-3-(1H-indol-3-yl)-4-nitrobutanals, one type of tryptamine precursors are of great interest for pharmaceutical and biological research. Herein, the Michael addition of aliphatic aldehydes to indolylnitroalkenes has been developed using (S)-diphenylprolinol trimethylsilyl ether as an organocatalyst, which provides the desired optically pure syn 2-alkyl-3-(1H-indol-3-yl)-4-nitrobutanal derivatives in up to 98% yield with up to >99:1 dr and >99% ee. To show the synthetic usefulness of this methodology, optically active 2-alkyl-4-nitro-3-(1-tosyl-1H-indol-3-yl)butan-1-ol and tryptamine derivatives are readily obtained by stepwise systematic transformations.
Assuntos
Aldeídos/química , Ácidos Graxos/química , Indóis/química , Nitrocompostos/química , Triptaminas/química , Catálise , Estrutura Molecular , EstereoisomerismoRESUMO
The catalytic synthesis of nitrogen-containing heterocycles is of great importance to medicinal and synthetic chemists, and also a challenge for modern chemical methodology. In this paper, we report the synthesis of pyrazolidine derivatives through a domino aza-Michael/hemiacetal sequence with chiral or achiral secondary amines as organocatalysts. Thus, a series of achiral pyrazolidine derivatives were obtained with good yields (up to 90%) and high diastereoselectivities (>20:1) with pyrrolidine as an organocatalyst, and enantioenriched pyrazolidines are also achieved with good results (up to 86% yield, >10/1 regioselectivity, >20:1 dr, 99% ee) in the presence of (S)-diphenylprolinol trimethylsilyl ether catalyst.
RESUMO
Optically active spirocyclohexaneoxindole motifs are very important building blocks for preparations of biologically active complexes, natural products, and pharmaceutical compounds. Herein, we report the syntheses of enantiopure spirocyclohexaneoxindoles through domino Michael-Aldol reactions between isatin derived alkenes and pentane-1,5-dial in the presence of diphenylprolinol silyl ether as an aminocatalyst. As a result, a series of multistereogenic and functionalized spirocyclohexaneoxindoles have been obtained in good yields with moderate diastereoselectivities and excellent enantioselectivities. In addition, electronic circular dichroism (ECD) spectroscopy and time-dependent density functional theory (TD-DFT) were used to investigate the rational structures of spirocyclohexaneoxindoles.
Assuntos
Aldeídos/química , Alcenos/química , Cicloexanos/química , Indóis/química , Isatina/química , Compostos de Espiro/química , Catálise , Ciclização , Cicloexanos/síntese química , Indóis/síntese química , Modelos Moleculares , Oxindóis , Compostos de Espiro/síntese química , EstereoisomerismoRESUMO
Non-naturally enantioenriched cis-ß-thio-α-amino acid derivatives were synthesized through one pot, cascade thio-Michael/ring opening reaction of aromatic thiols with (Z)-olefinic azlactones in good yields with high levels of diastereoselectivities and enantioselectivities, which was catalyzed by a chiral bifunctional thiourea-tertiary amine catalyst.