Bi- and Polycyclic Systems

Optically pure 7-oxabicyclo[2.2.1]hept-5-en-2-yl derivatives as new chirones 90MI55. 

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Maier and Schleyer (220) have studied the problem of the stability of bridgehead double bonds in bi- and polycyclic systems. They define an olefinic strain (OS) as the difference in strain energy between the olefin and its parent saturated... 

Sufficient information about the reaction has been gathered to allow fairly accurate predictions of yield as well as of stereo- and regioselectivity.176177 The reaction proceeds via the formation of hexacarbonylalkyne-dicobalt complexes and is remarkably tolerant of functional groups in both the alkyne and the alkene. The intramolecular Pauson-Khand reaction is an effective way of preparing bi- and polycyclic systems, and the cyclization of 1,6-heptenyne derivatives to give bicyclo[3.3.0]oct-l-en-3-ones has been the most popular application of the Pauson-Khand reaction in natural product synthesis [Eq. (17)]. 

Homophthalic anhydrides in synthesis of heteroeycies 84KGS1587. Metallation as key step in heterocyclic synthesis 83S957. a-Methylamino acids—heterocyclic derivatives, synthesis of 85MI21. Polysubstituted heteroeycies in syntheses of bi- and polycyclic systems ... 

Tethering the ene and yne reaction partners for Pauson-Khand cycloaddition was first conceived as a way to improve simultaneously the effective reactivity of simple alkene moieties and to provide access to a wider variety of bi- and polycyclic systems. Indeed, well over 100 examples of such cycloadditions have been published, mostly involving reactions of derivatives of 1,6-heptenyne to give bicyclo[3.3.0]oct-l-en-3-ones [cf. Eq. (37)] together with a smaller number of 1,7-octenynes, which afford bicyclo[4.3.0]non-l (9)-en-8-ones [81 c, 117]. The use of dry-state conditions [118] or additives such as amine oxides [119] has virtually revolutionized this field the cycloaddition shown in Eq. (52) is completed in 15 minutes( ) when promoted by NMO. 

The equilibrium position depends on the nature of the substituents and R. Ring-chain tautomerism is frequently observed in bi- and polycyclic systems, e.g. imidazole[2,3-e]tetrazole 3. An equilibrium with 2-azidoimidazole 4 is established by the action of bases. 

This solid-phase technique has made possible efficient syntheses of bi- and polycyclic systems from precursors frequently generated via Nicholas cations, (e.g. eq 60) and has been used for intermolecular reactions with methy lenecyclopropane (eq 61) and methylenecyclobutane to give spirocyclic cyclopentenone derivatives. (1) is the majorproduct when the alkyne is terminal (R = H), but only (2) was isolated when EtC2Et or Me3 SiC2Me were used. ... 

Emphasis is placed on simply substituted free bases. The problems of conformational equilibria in /V-alkylpiperidinium salts and N-quaternization reactions and the relationships of these to conformational equilibria in the free bases are not covered, since this area is a large one requiring separate treatment. In other relevant previous reviews, the topics include heterocyclic conformational analysis,3-7 interactions in azacyclic systems,8 the conformational analysis of piperidine,9 hexahydropyrimidines,10,11 hexahydropyri-dazines,12 quinolizidines,13 the conformational analysis of bi- and polycyclic... 

There are several cases of polycyclic triazolines, obtained by azide addition to the strained olefinic bond in bi- and tricyclic systems, that are susceptible to retro Diels-Alder reaction to yield 1-substituted triazoles. A well-established example is the monoadduct from norbornadiene and phenyl azide, which decomposes at 90-100°C to give 1-phenyltriazole and a cyclopentadiene (Scheme 138).2s 97—" 1 47 430 Similarly, the cycloadduct from the reaction of 7-oxabenzonorbornadiene and 1-azidoadamantane, when heated at 110°C, affords good yields of l-(l-adamantyl)-l,2,3-triazole in a retro Diels-Alder reaction.155... 

Pyrido[ 1,2-a]py rimidines represent a simple bicyclic ring system that contains a nitrogen-bridgehead condensed pyrimidine moiety. Synthetic methods for these compounds can often be applied to the preparation of similar bi- and polycyclic ring systems (e.g., benzologs, N-analogs, five membered congeners, and so on) and their reactivities are sometimes similar to those of the above-mentioned derivatives. 

Ring closure by valence isomerization s. 26, 757 prepn. of bi- and polycyclic conjugated jr-electron systems, aminodihydropentalens, s. R. Kaiser and K. Hafner, Ang. Ch. 85, 361 (1973)... 

Abstract The data on 6-fluoro-l,4-dihydroquinolin-4-oxo-3-carboxylic acids and their structural analogues accumulated in the literature for the last 10-15 years are reviewed. Synthetic approaches to the quinolone system, as well as all kind of structural modifications by incorporating substituents into 1-8 positions or by means of annelation have been discussed. The structure-activity relationships for antibacterial fluoroquinolones, as well as the data on other types of biological activity for the family of bi- and polycyclic fluoroquinolones are presented. The formation of complexes of fluoroquinolones with metals and their applications have been considered. The bibliography - 377 references. 

Dihydroxyfurazan reacts with bis-electrophiles in the presence of a base and a phase transfer catalyst to form furazano fused bicyclic or polycyclic systems (Scheme 174) (92URP1715808, 92URP1715809, 92URP1752734, 97MI8). 

When phosphaalkynes are exposed to bis- and tris(diazo) compounds, bis- or tris(l,2,4-diazaphosphol-5-yl) compounds are formed that may be further converted into a variety of novel heterocyclic systems. For example, bis- and tris[diazo(tri-methylsilyl)methyl]phosphanes 237 and 240 afforded bis- and tris(diazaphospho-lyl)phosphanes 238 and 241 after cycloaddition with terf-butylphosphaacetylene followed by a subsequent 1,5-silyl shift (Scheme 8.56) (300). Reaction with electrophilic halides at the Wsilyl functions allows the introduction of a heteroatom bridge between the diazaphosphole ring leading to polycyclic ring systems such as 239 and 242. 

The vast work reported on the chemistry of (3-lactams has demonstrated that (3-lactam systems are quite readily accessible through a number of different approaches, with newer versions still being reported. These molecules possess enough stability as to be suitable for the standard isolation, separation, and purification processes at both the laboratory and the industrial scales [35-37]. Recently, several review articles have highlighted the different methodologies for the steroselective syntheses of mono-, bi-, tri-, and polycyclic (3-lactams with associated biological activities [38—43],... 

Intramolecular oxidative cyclizations in the appropriately substituted phenols and phenol ethers provide a powerful tool for the construction of various practically important polycyclic systems. Especially interesting and synthetically useful is the oxidation of the p-substituted phenols 12 with [bis(acyloxy)iodo]-arenes in the presence of an appropriate external or internal nucleophile (Nu) leading to the respective spiro dienones 15 according to Scheme 6. It is assumed that this reaction proceeds via concerted addition-elimination in the intermediate product 13, or via phenoxenium ions 14 [18 - 21]. The recently reported lack of chirality induction in the phenolic oxidation in the presence of dibenzoyltar-taric acid supports the hypothesis that of mechanism proceeding via phenoxenium ions 14 [18]. The o-substituted phenols can be oxidized similarly with the formation of the respective 2,4-cyclohexadienone derivatives. 

One of the most versatile applications of [Os]-anisole chemistry is the efficient generation of complex polycyclic systems. Through the application of a variety of methodologies, anisole complexes have been used to generate a number of cyclic arrangements, including a bi-cyclo[2.2.2]octadiene, decalins, tetralins, and tricyclic arrays. 

Cyclopentadiene is more reactive towards diazoalkanes. It undergoes addition of diazomethane (and diazoethane) and thermal or photochemical deazetization of the adduct to give bi-cyclo[3.1.0]hex-2-ene or 6-methylbicyclo[3.1.0]hex-2-ene in good yield.Polycyclic systems incorporating strained cyclopentene units also react rapidly with diazoalkanes and cyclo-propanations via this route are relatively easy. Hence the addition of diazomethane to benz-valene 13 gave an 83% yield of the 4,5-dihydro-3//-pyrazole, which on photolysis gave tetra-cyclo[4.1.0.0 ". 0 ]heptane (27%) similar reactions are known for many other diazoalkanes. Addition of diazoethane to norborn-2-ene (14a) and thermal or photochemical... 

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