Molecular Lego. 1. Substrate-Directed Synthesis via Stereoregular Diels-Alder Oligomerizations (original) (raw)
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From Metacyclophanes to Cyclacenes: Synthesis and Properties of [6.8] 3 Cyclacene
Chemistry - A European Journal, 2009
[6] n Cyclacenes (1 with n = 10) and cyclo[n]phenacenes (2 with n = 10) as subunits of carbon nanotubes. . by utilizing methods to reduce the north and south pole of C 60 (Scheme 1). Our approach uses eight-membered rings as building blocks. The boat conformation of cyclooctatetraene provides excellent conditions to incorporate it in a conjugated medium sized p-system. In Scheme 2 we have shown the cases for linear cyclacenes in which four-and eight-membered as well as six-and eight-membered rings alternate. [3e] Recent quantum chemical calculations reveal that 6 (n = 3,4) and 7 (n = 3-8) should be thermodynamically stable species. The necessary bending of the smaller species is mainly achieved by a stronger bending of the flexible cyclooctatetraene rings.
Synthesis of Unique Scaffolds via Diels−Alder Cycloadditions of Tetrasubstituted Cyclohexadienes
Organic Letters, 2010
Diels-Alder cycloadditions of highly substituted cyclohexadienes derived from rhodium-mediated [2+2+2] cyclizations are reported. Reactive heterodienophiles, including singlet oxygen (1 O 2), 4substituted-1,2,4-triazoline-3,5-diones (TADs), and aryl-and acylnitroso compounds were employed, yielding novel heterocyclic products. Reactivity in Diels-Alder (DA) cycloadditions of cyclohexadienes is strongly influenced by steric constraints, often requiring forceful conditions or catalysis to promote the desired annulation.1 , 2 Unactivated, highly substituted cyclohexadienes, which can be accessed via transition metal-catalyzed [2+2+2] cyclizations, are relatively unreactive in intermolecular cycloadditions.2b , 3 Previously, we reported the rhodium-mediated intramolecular [2+2+2] cyclizations of tethered diyneenone substrates to produce cyclohexadiene systems which were subsequently aromatized with DDQ, giving highly substituted benzene rings. 4 Other groups have also reported the use of [2+2+2] cyclizations to generate cyclohexadienes with quaternized allylic centers which cannot aromatize.5 We became interested in the reactivity of these highly substituted, electronically unactivated diene systems in DA cycloadditions, particularly with heterodienophiles, as this would allow the creation of unique, densely functionalized scaffolds. The preparation of three model substrates 4a-c was straightforward employing methodology we previously reported (Scheme 1). 4 Diynyl esters 1a and 1b, prepared from sequential S N 2 displacements of 1,4-dibromobutyne, 4,6 were subjected to Weinreb amidations, followed by isopropenyl Grignard additions to give enediynes 3a and 3b. The desired [2+2+2] cyclizations were achieved under Rh(I)-catalyzed, microwave-promoted conditions to give racemic cyclohexadienes 4a and 4b in 90% and 91% yields, respectively. 4 Pyrrolidine substrate 4c was easily prepared from [2+2+2] cyclization of diyne 5 7 with excess methyl methacrylate 6. 5b
RSC Advances, 2018
The synthesis of propellanes containing bicyclo[2.2.2]octene via olefin metathesis approach is less explored. Herein, we describe a simple and convenient method to synthesize propellane derivatives containing a bicyclo[2.2.2]octene unit which are structurally similar to 11b-HSD1 inhibitors by sequential usage of the Diels-Alder reaction, C-allylation and ring-closing metathesis (RCM) as the key steps. Additionally, we expanded this approach to an endo-tricyclo[4.2.2.0 2,5 ]decene derivative which is a useful monomer for polymer synthesis and we have also synthesized basketene and anthracene-based propellanes using the same strategy.
Canadian Journal of Chemistry, 1995
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The reaction of norbornadiene with cyclopentadiene affords a good yield of 1,4,4a,5,8,8a-hexahpdro-1,4,5,8-exo-endodimethanonaphthalene, whose configuration was established through semihydrogenation followed by degradation to dicarboxylic acids of known structure, and through complete hydrogenation to the known saturated tetracyclic hydrocarbon. Oxidation of hexahydrodimethanonaphthalene furnished cis-bicyclo[3.3.0]octane-cis,cis,trans,trans-2,4,6,8-tetracarbo~~~~c acid.
Table of contents 1. General experimental information S3 2. Experimental procedures and characterization data S4 a. Synthesis of dienes S4 b. Synthesis of alkyl amides S5 c. General procedure for the Pd-catalyzed preparation of 2-piperidinones S10 d. Mechanistic experiments S27 Reaction with diene (E)-2m and (Z)-2m S27 Isolation of palladacycles S29 Reaction of palladacycles with diene 2a S32 e. Manipulation of the products S33 3. References S36 4. NMR spectral data S37 S3 1. General experimental information Reactions were conducted in dry solvents under Argon unless otherwise stated. Dry solvents were obtained from Acros Organics, Extra Dry over Molecular Sieves, and used without further purification. Pd(OAc)2 (98%) [3375-31-1] was obtained from Strem. All other chemicals were purchased from Sigma-Aldrich, Acros Organics, Alfa Aesar, Fluorochem or Abcr and they were used as received. All palladium-catalyzed reactions were carried without precautions to elude moisture or oxygen. The abbreviation "rt" refers to reactions carried out at a temperature between 21-25 ºC. Reaction mixtures were stirred using Teflon-coated magnetic stir bars. Thin layer chromatography (TLC) was carried out on pre-coated silica gel F254 plates with visualization under UV light or by dipping the plate into solutions of p-anisaldehyde or cerium nitratefollowed by heating. Column chromatography was performed on silica gel (40-60 μm) unless otherwise stated. NMR data was collected on Varian Mercury 300 MHz or Bruker AVIII 500 MHz spectrometers. Chemical shifts are given in ppm (δ) and are referenced to the residual CDCl3 solvent peak at 7.26 ppm (1 H NMR) and 77.16 ppm (13 C NMR). Conventional onedimensional (1D) 1 H NMR, 19 F NMR, 13 C{ 1 H} NMR, Distortionless Enhancement by Polarization Transfer Spectra (DEPT) and two-dimensional (2D) 1 H-1 H Correlation Spectroscopy (COSY), 1 H-1 H Nuclear Overhauser Effect Spectroscopy (NOESY), 1 H-13 C heteronuclear single quantum coherence (HSQC), 1 H-13 C Heteronuclear Multiple-Bond Correlation Spectroscopy (HMBC) experiments were recorded at room temperature under routine conditions. NMR data was analyzed using MestReNova NMR data processing software (http://mestrelab.com/). High Resolution Mass Spectra (HRMS) were performed at the CACTUS facility of the University of Santiago de Compostela on a Bruker micrOTOF spectrometer. X-ray crystallographic analysis of 3af, 4, 5 and 6 was performed at the CACTUS facility of the University of Santiago de Compostela. X-ray crystallographic analysis of 3aa was performed at the CACTI facility of the University of Vigo. S4 2. Experimental procedures and characterization data Synthesis of dienes Dienes 2a ((E)-buta-1,3-dien-1-ylbenzene), 2h (isoprene) and 2l (1,3cyclohexadiene) were commercially available. 2a and 2h were purchased from Aldrich and 2l from Acros Organics. Dienes 2b ((E)-1-(1,3-butadienyl)-4-nitrobenzene), 2c ((E)-1-(1,3-butadienyl)-3-fluorobenzene), 2d ((E)-1-(1,3-butadienyl)-2methoxybenzene), 2e ((E)-deca-1,3-diene), 2i ((E)-(2-methylbuta-1,3-dien-1yl)benzene), 2k (1-vinylcyclohex-1-ene) and (E) and (Z)-2m (tertbutyldimethyl(penta-2,4-dien-1-yloxy)silane) were synthesized from the corresponding aldehyde via Wittig reaction according to the literature. 1 Diene 2g (ethyl (E)-penta-2,4-dienoate) was also synthesized with a method previously reported in literature. 2 Spectral data recorded was in agreement with the previously reported. Diene 2f ((E)-N-methoxy-N-methylhepta-4,6-dienamide) was prepared from the corresponding ester, already prepared in the literature, 3 following the procedure shown below. i PrMgCl (2.0 M in THF, 15 mL, 30 mmol, 4.2 equiv) was added to a suspension of CH3NH(OCH3). HCl (1.46 g, 14.63 mmol, 2 equiv) in THF (71 mL), under Ar atmosphere, at-15 ºC. The resulting mixture was stirred for 20 minutes. Then, the ester (1 g, 7.13 mmol, 1 equiv.) was added and the solution was warmed to 0 °C. The mixture was stirred for 3 h before NH4Cl (sat.) (25 mL) was added to quench the reaction. The layers were separated, and the aqueous layer was extracted with EtOAc (3 × 50 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4 and concentrated in vacuo. The crude product was purified by column flash chromatography on silica gel (20 to 60% EtOAc/hexanes) to give the diene 2f as a pale-yellow oil (1.19 g, 99%). 1 H NMR