RESUMO
A bifunctional tertiary amine-squaramide-catalyzed enantioselective Mannich-type addition of available allomaltol to N-protected aldimines was developed. The resulted adducts were readily transformed into non-proteinogenic α-amino acids and their derivatives were not easily accessible by other methods via oxidative fragmentation, esterification, amidation and deprotection reactions. The absolute (S)-configuration of the thus obtained α-amino acids was established by comparison of the N-Ts-PheGly optical rotation sign with the reported data.
Assuntos
Aminas , Aminoácidos , Estereoisomerismo , Catálise , Aminoácidos/química , Aminas/químicaRESUMO
2-Nitroallylic carbonates, a new class of "green" 1,3-bielectrophilic reagents for organic synthesis and catalysis, have been prepared. The bifunctional tertiary amine-catalyzed asymmetric [3 + 3] annulations of cyclic enols with these reagents occur much faster than corresponding reactions with 2-nitroallylic esters and produce no acidic by-products poisoning the catalyst. Furthermore, 2-nitroallylic carbonates enable highly enantioselective one-pot synthesis of a variety of fused dihydropyrane derivatives from available precursors bearing pharmacophoric fragments.
RESUMO
A correlation between the equilibrium ratio of tautomeric products generated by the asymmetric Michael reactions of cyclic carbon acids with ß,γ-unsaturated α-keto esters and the chemical shift of the α-proton in starting nucleophilic substrates was revealed which makes equilibration predictable. New tetrahydropyran-fused benzo[a]phenazins were enantioselectively (up to 99% ee) synthesized from ß,γ-unsaturated α-keto esters and benzo[a]phenazin-5-ol, a powerful anti-cancer agent sAJM589. Facile recyclability of catalyst Ia in the catalytic reactions was demonstrated.
RESUMO
A very simple and highly efficient C2-symmetric tertiary amine-squaramide organocatalyst for asymmetric Michael reactions has been elaborated. In the presence of only 1 mol % of this catalyst, kojic acid derivatives and ß-dicarbonyl compounds reacted with nitroolefins, affording the corresponding adducts in a nearly quantitative yield with an enantioselectivity up to 99% ee. The kojic acid-derived adducts could be efficiently produced under "green" conditions (in 96% EtOH or pure water). Moreover, due to the very low solubility in organic solvents, the developed nonsupported catalyst could be readily recovered and reused in catalytic reactions up to 7 times. Utmost availability (one-step synthesis without chromatographic purification), high level of stereoinduction, low efficient loading, and recyclability make it attractive for industrial application in the pharmaceutical industry.
RESUMO
An efficient sterically hindered C2-symmetric bifunctional tertiary amine-squaramide organocatalyst for the asymmetric Michael addition/hemiketalization domino reaction of kojic acid derivatives with ß,γ-unsaturated α-ketoesters has been designed. Pharmacology-relevant functionalized 2,3,4,8-tetrahydropyrano[3,2-b]pyran derivatives were produced over the catalyst in as low as 1 mol% with up to 99% yield and 99% ee. The procedure is at least 30-fold scalable and the catalyst is readily reusable in the catalytic reaction via acid-base extraction. Acylation of the products with (S)- or rac-ibuprofen and with undec-10-enoic acid afforded the corresponding chiral esters containing two privileged pharmacophoric motifs.
RESUMO
Novel C2-symmetric N,N'-bis(2-amino-1,2-diphenylethyl)squaramides with 1,2-di(pyridin-2-yl)ethane and 1,2-diphenylethane spacer groups were designed and applied as organocatalysts in asymmetric additions of 4-hydroxycoumarin and 4-hydroxy-6-methyl-2H-pyran-2-one to α,ß-unsaturated ketones. Both enantiomers of the anticoagulant warfarin and its analogs were prepared in up to 96% yield and with 96% ee. Recyclability of the developed catalysts and synthetic utility of the prepared Michael adducts for asymmetric synthesis of potential chiral medications via acylation reactions were demonstrated.
Assuntos
Diaminas/química , Quinina/análogos & derivados , Varfarina/química , Varfarina/síntese química , Catálise , Técnicas de Química Sintética , Quinina/química , EstereoisomerismoRESUMO
A new efficient and highly recyclable organocatalyst has been developed for asymmetric cross-aldol reactions under neat conditions in ketone-ketone, ketone-aldehyde, and aldehyde-aldehyde systems. The catalyst features two prolinamide fragments and a C2-symmetrical (1,2-diaminoethane-1,2-diyl)bis(N-methylpyridinium) group. The catalyst retained high activity and excellent stereoselection over the operating period of more than 830 h (25 cycles). An ab initio theoretical investigation explained the absolute configuration of the products and different stereoinduction levels for designed diastereomeric organocatalysts.