RESUMO
Cycloaddition reactions are among the most important tools for the construction of cyclic compounds in organic synthesis, since these reactions are vital to access natural products and biologically active compounds. Organocatalysis plays an increasingly pivotal role in these reactions, often allowing several stereocenters to be selectively created and integrated in the target molecule. Among the large number of efficient types of organocatalysts available, the diarylprolinol silyl ethers have been established as one of the most frequently used in aminocatalysis allowing for novel activation modes and reaction concepts. In this review, we will focus on the different activation modes made available by the diarylprolinol silyl ether system with the aim of highlighting their applicability in asymmetric cycloadditions for the assembly of complex molecular architectures.
RESUMO
A novel enantioselective organocatalytic strategy is presented for the synthesis of tetrahydrofurobenzofuran and methanobenzodioxepine natural product core structures. The strategy is based on a pair of divergent reaction pathways in which hydroxyarenes react with γ-keto-α,ß-unsaturated aldehydes, catalyzed by a chiral secondary amine. One reaction pathway, which leads to chiral 5,5-fused acetals with two stereocenters-the tetrahydrofurobenzofuran scaffolds-proceeds in moderate yields and up to 96 %â ee. The other reaction pathway provides 5,6-bridged methanobenzodioxepine scaffolds with three stereocenters in moderate to good yields and up to 95 %â ee. The reaction is remarkable as it can proceed with catalyst loadings as low as 0.25â mol %, providing one of the highest known turnover numbers in iminium ion catalysis. Furthermore, the hemiacetal tetrahydrofurobenzofuran can undergo functionalizations including reduction, oxidation, and allylation. Finally, the effects involved in the substrate control for the divergent pathways, based on both experimental and computational studies, have been investigated. A model involving steric, electronic and stereoelectronic interactions is discussed to rationalize the observed selectivities.
RESUMO
The treatment of readily available N-alkynyl-5-iodo-6-sulfamido-pyrimidines with iPrMgClâ LiCl followed by a transmetalation with CuCNâ 2 LiCl produces, after intramolecular carbocupration, metalated pyrrolo[2,3-d]pyrimidines. Quenching of these pyrimidines with allylic halides or acid chlorides results in polyfunctional pyrrolo[2,3-d]pyrimidines. Further reaction with ICl and a Negishi cross-coupling, using PEPPSI-iPr as the catalyst, furnishes fully substituted N-heterocycles. A formal synthesis of the marine alkaloid rigidinâ A has been achieved as well as the preparation of a derivative of 7-azaserotonine, related to the natural hormone serotonin.
Assuntos
Alcaloides/síntese química , Cobre/química , Piridinas/síntese química , Pirróis/síntese química , Serotonina/análogos & derivados , Alcaloides/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Catálise , Ciclização , Piridinas/química , Pirróis/química , Serotonina/síntese química , Serotonina/químicaRESUMO
The Lewis acid MgCl2 allows control of the metalation regioselectivity of uracils and uridines. In the absence of the Lewis acid, metalation of uracil and uridine derivatives with TMPMgCl·LiCl occurs at the position C(5). In the presence of MgCl2, zincation using TMP2Zn·2LiCl·2MgCl2 occurs at the position C(6). This metalation method provides easy access to functionalized uracils and uridines. Using TMP2Zn·2LiCl·2MgCl2 also allows to functionalize cytidine derivatives at the position C(6).
Assuntos
Citidina/química , Ácidos de Lewis/química , Cloreto de Magnésio/química , Uracila/química , Uridina/química , Técnicas de Química Combinatória , Citidina/síntese química , Estrutura Molecular , Compostos Organometálicos/química , Estereoisomerismo , Uracila/síntese química , Uridina/síntese química , Zinco/químicaRESUMO
The influence of the metal on the nucleophilic reactivities of indenyl metal compounds was quantitatively determined by kinetic investigations of their reactions with benzhydrylium ions (Ar2 CH(+) ) and structurally related quinone methides. With the correlation equation log k2 =sN (N+E), it can be derived that the ionic indenyl alkali compounds are 10(18) to 10(24) times more reactive (depending on the reference electrophile) than the corresponding indenyltrimethylsilane.
RESUMO
Highly functionalized aldol-type products bearing a ß-quaternary center and a stereoselectively controlled γ-hydroxy function are readily prepared by the diastereoselective addition of an allylic zinc reagent embedded in an isoxazole ring to various aromatic and heteroaromatic aldehydes, in the presence of Lewis acids, such as MgCl2 or LaCl3â 2 LiCl. After reductive cleavage of the N-O bond by using Fe, NH4Cl, aldol-type products bearing a stereocontrolled ß-quaternary center and a γ-hydroxy group were observed. The benzylic reactivity of the isoxazolylmethylzinc reagent towards other electrophiles, such as acid chlorides, aryl and allylic halides, as well as aldehydes in the presence of BF3â OEt2 are also described.
Assuntos
Aldeídos/química , Isoxazóis/química , Zinco/química , Indicadores e Reagentes , Ácidos de Lewis/química , Modelos Moleculares , Compostos Organometálicos/química , EstereoisomerismoRESUMO
A Lewis acid-triggered zincation allows the regioselective metalation of various chromones and quinolones. In the absence of MgCl(2), a C(3) zincation is observed, whereas in the presence of MgCl(2) or a related Lewis acid, C(2) zincation occurs. Applications to a natural flavone, isoflavone, and quinolone are shown.
Assuntos
Cromonas/química , Flavonas/síntese química , Isoflavonas/síntese química , Ácidos de Lewis/química , Quinolonas/química , Zinco/química , Produtos Biológicos/síntese química , Cromonas/síntese química , Quinolonas/síntese química , EstereoisomerismoRESUMO
The full functionalization of the pyrazole ring was achieved by successive regioselective metalations using TMPMgCl x LiCl and TMP(2)Mg x 2 LiCl. Trapping with various electrophiles led to trisubstituted pyrazoles. An application to the synthesis of the acaricide Tebufenpyrad is reported.