Síntese de ligantes do tipo imidazolina e aplicação em reação de Henry diastereo e enantiosseletiva
Data
2022-01-19
Autores
Vicente, Ariadne de Jesus 
Orientadores
Rodrigues, Alessandro
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A quiralidade molecular é um importante conceito em estereoquímica e bioquímica. Sua relevância é
fundamental em diversas áreas da ciência, tais como a química farmacêutica e química sintética. Neste contexto,
a catálise assimétrica homogênea com uso de metais de transição complexados a ligantes, na qual reações
orgânicas catalisadas por ácidos de Lewis em ambientes quirais são um dos principais métodos para controlar a
estereoquímica na formação de produtos. Para este trabalho foram sintetizados cinco ligantes contendo o
heterociclos do tipo imidazolina a partir da (R,R) ou (S,S)-1,2-difenildiamina. Os ligantes do tipo N-Bocimidazolina piridina (I) e N-Boc-imidazolina-quinolina (II) são inéditos, sendo obtidos respectivamente em duas e cinco etapas
reacionais com rendimentos globais de 81% e 67%. Os ligantes N,N-(bis)imidazolina-piridina (III) e N-Boc-
(bis)imidazolina (IV) foram preparados em cinco etapas, com rendimentos de 52%, e 80%, enquanto que o N-Ts-
(bis)imidazolina (VI) com 65%, foi sintetizado em três etapas. Estes ligantes foram complexados a diferentes sais
de cobre II in situ e aplicados em reações de Henry(nitroaldol), entre benzaldeído e nitroetano. de acordo com a
condição já otimizada em meio de tetraidrofurano, a 0 °C, pelo período de 24 h, utilizando-se como base a N-etil morfolina; dos quais o ligante V desempenhou melhor controle estereosseletivo, com uma razão
diasterosseletiva de 1:2, e excessos enantioméricos de 57% para o produto anti e 83% para o sin. A etapa de
avaliação do escopo reacional foi realizada usando uma série de 20 aldeídos contendo grupos alquílicos ou
aromáticos. Dos aldeídos submetidos à reação de Henry, foram obtidos produtos com 16 aldeídos com
rendimentos de 57 até 84%, razão diastereoisomérica até 10:1 e excesso enantiomérico até 95%.
Molecular chirality is an important concept in stereochemistry and biochemistry. Its relevance is fundamental in several areas of science, such as: pharmaceutical chemistry and synthetic chemistry. In this context, homogeneous asymmetric catalysis using transition metals complexed to chiral ligands, in which organic reactions catalyzed by Lewis acids in chiral environments are one of the main methods to control the stereochemistry in the formation of chiral products. For this dissertation, five chiral ligands containing imidazoline-type heterocycles were synthesized from (R,R) or (S,S)-1,2-diphenyldiamine. The N-Boc-imidazolinepyridine (I) and N-Boc-imidazoline-quinoline (II) type ligands are novel, being obtained respectively in two and five reaction steps with 81% and 67% overall yields. The N,N-(bis)imidazoline-pyridine (III) and N-Boc- (bis)imidazoline (IV) chiral ligands were prepared in five steps, with 52% and 80% respectively yields, while the N-Ts-(bis)imidazoline (VI) was synthesized in three steps with 65% yield. These ligands were in situ complexed to different copper(II) salts and applied in Henry reactions (nitroaldol) between benzaldehyde and nitroethane with several screened reaction conditions. The optimized reaction condition includes tetrahydrofuran as the solvent, at 0 °C, for a period of 24 h, using N-ethyl-morpholine as the base, and the ligand V performed better stereoselective control, with a diastereoselective ratio of 1:2, and enantiomeric excesses of 57% for the anti product and 83% for the syn-product. The reaction scope evaluation step was carried out using a series of 20 aldehydes in total, containing alkyl or aromatic substituent groups. From the aldehydes submitted to Henry reaction, products with 16 aldehydes were obtained with yields from 57 to 84%, diastereoisomeric ratio up to 10:1 and enantiomeric excesses up to 95%.
Molecular chirality is an important concept in stereochemistry and biochemistry. Its relevance is fundamental in several areas of science, such as: pharmaceutical chemistry and synthetic chemistry. In this context, homogeneous asymmetric catalysis using transition metals complexed to chiral ligands, in which organic reactions catalyzed by Lewis acids in chiral environments are one of the main methods to control the stereochemistry in the formation of chiral products. For this dissertation, five chiral ligands containing imidazoline-type heterocycles were synthesized from (R,R) or (S,S)-1,2-diphenyldiamine. The N-Boc-imidazolinepyridine (I) and N-Boc-imidazoline-quinoline (II) type ligands are novel, being obtained respectively in two and five reaction steps with 81% and 67% overall yields. The N,N-(bis)imidazoline-pyridine (III) and N-Boc- (bis)imidazoline (IV) chiral ligands were prepared in five steps, with 52% and 80% respectively yields, while the N-Ts-(bis)imidazoline (VI) was synthesized in three steps with 65% yield. These ligands were in situ complexed to different copper(II) salts and applied in Henry reactions (nitroaldol) between benzaldehyde and nitroethane with several screened reaction conditions. The optimized reaction condition includes tetrahydrofuran as the solvent, at 0 °C, for a period of 24 h, using N-ethyl-morpholine as the base, and the ligand V performed better stereoselective control, with a diastereoselective ratio of 1:2, and enantiomeric excesses of 57% for the anti product and 83% for the syn-product. The reaction scope evaluation step was carried out using a series of 20 aldehydes in total, containing alkyl or aromatic substituent groups. From the aldehydes submitted to Henry reaction, products with 16 aldehydes were obtained with yields from 57 to 84%, diastereoisomeric ratio up to 10:1 and enantiomeric excesses up to 95%.
Descrição
Citação
Síntese de ligantes do tipo imidazolina e aplicação em reação de Henry diastereo e enantiosseletiva.