1,5 -Cyclooctadienes cyclization

The cyclohexadiene derivative 130 was obtained by the co-cyclization of DMAD with strained alkenes such as norbornene catalyzed by 75[63], However, the linear 2 1 adduct 131 of an alkene and DMAD was obtained selectively using bis(maleic anhydride)(norbornene)palladium (124)[64] as a cat-alyst[65], A similar reaction of allyl alcohol with DMAD is catalyzed by the catalyst 123 to give the linear adducts 132 and 133[66], Reaction of a vinyl ether with DMAD gives the cyclopentene derivatives 134 and 135 as 2 I adducts, and a cyclooctadiene derivative, although the selectivity is not high[67]. 

The synthetic route represents a classical ladder polymer synthesis a suitably substituted, open-chain precursor polymer is cyclized to a band structure in a polymer-analogous fashion. The first step here, formation of the polymeric, open-chain precursor structure, is AA-type coupling of a 2,5-dibromo-1,4-dibenzoyl-benzene derivative, by a Yamamoto-type aryl-aryl coupling. The reagent employed for dehalogenation, the nickel(0)/l,5-cyclooctadiene complex (Ni(COD)2), was used in stoichiometric amounts with co-reagents (2,2 -bipyridine and 1,5-cyclooctadiene), in dimethylacetamide or dimethylformamide as solvent. 

Among transition metal complexes used as catalysts for reactions of the above-mentioned types b and c, the most versatile are nickel complexes. The characteristic reactions of butadiene catalyzed by nickel complexes are cyclizations. Formations of 1,5-cyclooctadiene (COD) (1) and 1,5,9-cyclododecatriene (CDT) (2) are typical reactions (2-9). In addition, other cyclic compounds (3-6) shown below are formed by nickel catalysts. Considerable selectivity to form one of these cyclic oligomers as a main product by modification of the catalytic species with different phosphine or phosphite as ligands has been observed (3, 4). 

The strained c ,traws-l,3-cyclooctadiene 1 cyclizes quantitatively at 80 °C to the bicy-clo[4.2.0]octene 2 (equation 3). The higher homologue 3 exists in equilibrium with the bicyclic isomer 4 above 175 °C (equation 4)4. 

Nevertheless, a different selectivity has really been observed83 in bromofluorination reactions of 1,5-cycloalkadienes with NBS/Et3N-3HF or Olah s reagent. The reaction of 1,5-cyclooctadiene (3) with the former reagent yields mainly the 1,2-addition product 52, but when the reaction is carried out with Olah s reagent only compounds 53 and 54, arising from the usual transannular jr-cyclization, are formed (equation 53). 

In the first total synthesis of kelsoene (rac-l) [7, 8], commercially available 1,5-cyclooctadiene (11) was chosen as the starting material (Scheme 3). Oxidative cyclization with a mixture of PdCl2 and Pb(OAc)4 in acetic acid led to the formation of a diquinane diacetate [13] that was saponified to give... 

Synthesis of antx-a has been done through a ring expansion of cocaine (20), from 1, 5-cyclooctadiene (21) and by intramolecular cyclization between an iminium salt and a nucleophilic carbon atom (22). The structure of antx-a is given in Fig. 1. 

Ikegami has devised an interesting approach based upon 1,3-cyclooctadiene monoepoxide as starting material (Scheme LX) Transannular cyclization, Sharpless epoxidation, and silylation leads to 638 which is opened with reasonable regioselec-tivity upon reaction with l,3-bis(methylthio)allyllithium. Once aldehyde 639 had been accessed, -amyllithium addition was found to be stereoselective, perhaps because of the location of the te -butyldimethylsilyloxy group. Nevertheless, 640 is ultimately produced in low overall yield. This situation is rectified in part by the initial formation of 641 and eventual decarboxylative elimination of 642 to arrive at 643. An additional improvement has appeared in the form of a 1,2-carbonyl transposition sequence which successfully transforms 641 into 644... 

Mn(OAc)3-mediated reaction of acetylacetone with 1,5-cyclooctadiene (137) leads to the formation of a cis-fused bicyclic compound (138), through the addition of a acetylacetonyl radical to 1,5-cyclooctadiene and subsequent intramolecular radical cyclization (eq. 4.48). 

The reactivity of different dienes towards 4-(N,N-dimethylamino)phenyl cation (6) has been studied, and for open-chain dienes, such as 2,5-dimethyl-2,4-hexadiene, only the trans-pentadienylaniline is found in a 52% yield [30], In the case of cyclic dienes, transannular cyclization takes place, leading to an arylnortricyclene from norbornadiene and to l-arylbicyclo[3.3.0]octanes from 1,5-cyclooctadiene in moderate yields (Scheme 10.18) [30]. 

Ishii and coworkers developed a Mn(OAc)2-catalyzed hydrophosphonation of alkenes 40 (Fig. 47) [271]. The active Mn(III) catalyst is generated by reaction of Mn(OAc)2 with oxygen. Hydrogen abstraction from diethyl phosphite 169 forms a phosphonyl radical, which adds to 40. The resulting alkyl radical is reduced by 169 to continue the chain reaction. Alkylphosphonates 170 were isolated in 51-84% yield. With (3-pinene a cyclobutylcarbinyl radical ring opening was observed in 32% yield, while 1,5-cyclooctadiene underwent a tandem radical addition/ transannular 5-exo cyclization (cf. Fig. 38). 

Diethyl malonate or ethyl cyanoacetate 187 afforded bicyclo[3.3.0]octane derivatives 188 in a tandem radical addition/transannular 5-exo cyclization sequence with cyclooctadiene 131 in 76 and 78% yield, respectively [275]. (4-Pentenyl)arenes were employed in a similar tandem radical addition/radical... 

Although some nucleophilic alkenes and cyclopentadiene [1] upon treatment with DIB readily added two acetoxy groups, generally isolated double bonds are inert under mild conditions. An interesting reaction of preparative importance was the intramolecular cyclization of 1,5-cyclooctadiene. 

Stereoselective radical cyclization of 1,5-cyclooctadienes. Winkler and Sridar14 have noted transannular effects on the stereochemistry of cyclization of these octadienes (equation I). Thus radical cyclization of cis-1 and of the corresponding ketone (3) is highly frans-selective and is more rrans-selective than that of the monosubstituted diene 5. Cyclization of a 3,8-disubstituted cyclooctene is... 

Stereoselective formation of carbocycles has been carried out through [RhCl(cod)]2 (cod = cyclooctadiene) catalyzed reaction of alkenylzirconocene chloride to co-carbonyl carboxymide <07TL6471>. When the camphor sultam auxiliary is incorporated into amide 206, the Rh(I)-catalyzed reaction of alkenylzirconocene chloride 207 forms the cyclization product 211 with high diastereoselectivity. The tt-facial differentiation of the double bond in 206 for the initial attack of vinyl group can be explained by taking into consideration either of the reactive conformers A or B. No matter which reactive conformer is involved, the attack of the vinyl group to the less crowded C p si-face would account for the observed chirality. 

When heated with dirhenium dodecacarbonyl, both 1,3- and 1,5-cyclooctadiene experience transannular cyclization with formation of the complex 176.2S3 An X-ray crystal structure analysis of 176 is available. 

One of the most popular methods for creating the anatoxin-a skeleton is by transannular cyclization of a suitably substituted cyclooctene. This approach was used in the first synthesis of racemic anatoxin-a (Campbell et al. 1979). They carried out two different methodologies in order to reach the 9-azabicyclo[4.2.1]nonane structure (Scheme 7.3). The 1,5-cyclooctadiene (10) starting compound was transformed into the methyl amine 11 which was treated with hypobromous acid to produce the desired bicycle 12 as a mixture of diastereoisomers in 29% overall yield, with some amount of the azabicyclo[3.2.1] analogue (Bastable etal. 1972). 

An intramolecular reaction of 1,5- and 1,6-enynes with isonitriles takes place in the presence of Ni(COD>2 (COD = 1,5-cyclooctadiene) and phosphines, giving bicyclic cyclopentenone imines (equation 5). Stereochemical characteristics in substituted systems appear to pardlel those in the intramolecular Pauson-Khand enynes with substituents in propargylic positions cyclize preferentially to products in which those substituents occupy exo positions relative to the newly created ring fusion. It is likely that these reactions proceed via similar mechanisms involving insertion into bonds of metallacycles, although the order of incorporation of the three two-electron systems into the precursor to the final product is open to question in the nickel system. 

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