RESUMO
A general route to linear triquinanes including a formal synthesis of (+/-)-Delta(9(12))-capnellene is described. This cascade strategy combines an intramolecular Diels-Alder reaction tandem metathesis protocol to generate the linear cis-anti-cis-tricyclo[6.3.0.0(2,6)]undecane skeleton directly. Significantly, the ring-closing-ring-opening-cross-metathesis (RCM-ROM-CM) sequence with our norbornene adducts is the only observed mechanism.
RESUMO
A short (six steps from 17), versatile route to the tricyclic core of Vinigrol is described. A Lewis acid catalyzed and self-assembled Diels-Alder (LACASA-DA) reaction from the homoallylic cross-conjugated trienol 15 with N-methylmaleimide afforded the monoadduct 17 with diastereo-, regio-, and chemoselective control. Oxidation and installation of an acetylene (Ohira's reagent) followed by further manipulations afforded trienone 24. The second intramolecular Diels-Alder (at 45 degrees C) reaction assembled the tricyclic skeleton 25 directly. The configuration of 25 was confirmed by X-ray analysis.
Assuntos
Diterpenos/síntese química , Compostos Heterocíclicos com 3 Anéis/química , Cristalografia por Raios X , Diterpenos/química , Modelos Moleculares , Estrutura MolecularRESUMO
Four new classes of organic solvent soluble ethynylpentacene derivatives (2,9-, 2,10-, 2,6,9,13-, 2,6,10,13-) have been prepared by complementary, versatile, double Diels-Alder strategies. Functional groups on the A, C, and E rings can be manipulated to increase the solubility, modulate the electronics, and alter the solid-state packing. Cycloaddition reactions with diene 2 and 1,4,5,8-anthradiquinone (3) or ortho-quinodimethane 19 with 1-butyl-3-methylimidazolim iodide (18) as the iodide source (a significant improvement over NaI) and benzoquinone (20) followed by in situ aromatization afforded the quinones 4, 5, 21, and 22, respectively. For the 2,9- and 2,10- families, a one-pot desilylation/triflation was developed. Palladium(0) coupling and reductive aromatization afforded 2,9-di(triisopropylsilylethynyl)pentacene (10) and 2,10-di(triisopropylsilylethynyl)pentacene (11), respectively. Photodimerization of these pentacenes afforded the air-stable [4 + 4] cycloaddition pentacene precursors (tetrakisnaphthotricyclo[4.2.2.22,5]dodecanes, 12-15). Thermal cycloreversion of the dimers ( approximately 13 J/g, approximately 4 kcal/mol) produces the parent pentacenes (10 or 11). The tetrasubstituted family utilized a parallel route with extra versatility as the timing of the Grignard and palladium(0) coupling step may be varied depending upon the functional group combinations desired. The subsequent reactions provided the tetraethynylpentacenes 28-30, 33-35 (para-isomers), and 38 (meta-isomer). X-ray crystallography analysis of 28, 29, and 33 revealed various pi-pi stacked packing motifs that differ from the unfavorable herringbone pattern of pentacene.
Assuntos
Alcinos/química , Hidrocarbonetos Policíclicos Aromáticos/química , Alcinos/síntese química , Varredura Diferencial de Calorimetria , Cristalografia por Raios X , Ciclização , Dimerização , Modelos Moleculares , Fotoquímica , Hidrocarbonetos Policíclicos Aromáticos/síntese química , Espectrometria de Fluorescência , Espectrofotometria UltravioletaRESUMO
The sequential control of diene-transmissive Diels-Alder reactions to expand their versatility for natural product synthesis and the preparation of diversity oriented libraries is described. Self-assembly of the components (trienol 5 and methyl acrylate) via a Lewis acid template proceeds with regio-, diastereo-, and enantioselective [(S)-BINOL added] control to the monoadduct. In contrast, no cycloaddition reaction occurred at 22 degrees C in the absence of catalyst. This protocol obliterates the necessity of tether installation for an intramolecular cyclization. [reaction: see text].
RESUMO
Magnesium mediated carbometalation (Grignard addition) to appropriate propargyl alcohols to synthesize a cross-section of variably substituted alpha,beta-unsaturated gamma-sultines is described. Thio-rofecoxib, a selective COX-2 inhibitor (12), is synthesized by this method and its IC(50), microM COX-1 and COX-2 inhibition, and whole blood stability values reported.
Assuntos
Inibidores de Ciclo-Oxigenase/síntese química , Lactonas/síntese química , Sulfonas/síntese química , Carbono/química , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/farmacologia , Humanos , Lactonas/farmacologia , Magnésio/química , Proteínas de Membrana , Prostaglandina-Endoperóxido Sintases/fisiologia , Sulfonas/farmacologiaRESUMO
A new strategy for the aryl annulation of cyclic ketones is described. Palladium(0) coupling of a propargyl alcohol with the enol triflate of a ketone and addition of vinylmagnesium chloride generates a triene as a magnesium chelate that may be quenched with an electrophile. In some cases, the triene cyclizes under the reaction conditions. Aromatization is accomplished by exposure to manganese dioxide or dichlorodicyanoquinone (DDQ). [reaction: see text]
RESUMO
[reaction: see text] The synthesis of various tetrasubstituted alkenes and dienes in a regio- and stereocontrolled manner is described. This three-component coupling strategy involves the addition of Grignard reagents to propargyl alcohols followed by palladium(0)-mediated cross-coupling with aryl or vinyl halides. This protocol has been applied to the synthesis of (Z)-Tamoxifen and related mimics.
Assuntos
Alcenos/síntese química , Magnésio/química , Paládio/química , Tamoxifeno/síntese química , Anticarcinógenos/síntese química , Compostos Organometálicos/química , Estereoisomerismo , Tamoxifeno/análogos & derivadosRESUMO
[structure: see text] The syntheses of two distinct families of phenylyne helical cyclophanes with potential for organic materials are described. The meta-bonded atropisomers afford interesting bowtie-like and butterfly-like conformers from a palladium(0), copper-mediated coupling sequence. Molecular modeling revealed the contrasting stereochemistry in these systems from differential molecular folding pathways during cyclization. The interplanar separation of the superimposed aromatic rings is approximately 3.5 A.
RESUMO
[reaction: see text] Copper-mediated oxidative coupling of 3 afforded the strained product 4 from intramolecular cyclization rather than the triply bridged cyclophane 5 from dimerization. X-ray analysis of the bromo derivative 15 confirmed the distorted nature of the butadiyne bridge (bond angles 164.1 degrees and 153.4 degrees). The distortion in the strained triple bond is reflected in its cycloaddition reactivity. Cyclopentadiene and 1,3-cyclohexandiene afforded the new adduct macrocycles 16 and 17, respectively.