Polycyclic compounds => alkene

A interesting and useful reaetion is the intramolecular polycyclization reaction of polyalkenes by tandem or domino insertions of alkenes to give polycyclic compounds[l 38]. In the tandem cyclization. an intermediate in many cases is a neopentylpalladium formed by the insertion of 1,1-disubstituted alkenes, which has no possibility of /3-elimination. The key step in the total synthesis of scopadulcic acid is the Pd-catalyzed construction of the tricyclic system 202 containing the bicyclo[3.2. Ijoctane substructure. The single tricyclic product 202 was obtained in 82% yield from 201 [20,164). The benzyl chloride 203 undergoes oxidative addition and alkene insertion. Formation of the spiro compound 204 by the intramolecular double insertion of alkenes is an exam-ple[165]. 

It has been shown, however, that such catalysts may contain protons, either by design or because of the difficulty in removing all traces of moisture, and these protons have been shown to be superacidic with Hammett acidities up to —18. These protons will also play some role in the catalytic activity of these ionic liquids in practical situations. Ionic liquids in which superacidic protons have deliberately been generated by addition of small amounts of water, HCl or H2SO4 have been used to catalytically crack polyethene under relatively mild conditions. The main products are mixed C3-C5 alkanes, which would be a useful feedstock from waste polyethene recycling. In contrast to other cracking procedures no aromatics or alkenes are produced, although small amounts of polycyclic compounds are obtained. 

Palladium-catalyzed cyclization of alkenes and alkynes were reported by Balme and co-workers.143 144 Intramolecular carbopalladation occurs to give polycyclic compounds. It has been shown that the nucleophile type has a large influence on the cyclization process. Both 5-exo- and 6-endo-cyclization are observed for substrates with nitrile (116 and 118) and ester (120, 122, and 124) substituents, respectively (Scheme 36). When a mixed nucleophile (CN and C02Me) is used, a mixture of 5-exo and 6-endo products is obtained. The chemoselectivity is controlled by the size of the nucleophile used. The stereochemistry of the initial double bond plays an important role on the stereoselectivity of the cyclization. (Z)-olefins (118 and 120) and (/. )-olefins (116 and 124) afford as- (119 and 121) and trans-cyclization products (117 and 123), respectively. 

A concise collection of some modem methods of radical formation via rupture of C-E, C-G and C-A bonds, as well as from alkenes and cyclopropanes, by metals, organometallic hydrides, and photochemical and electrochemical means, are given in the last Chapter of Giese s book [28]. For some examples of radical generation and reactions leading to cyclic and polycyclic compounds see next Chapter (Heading 6.1.3). 

Fig. 4.14. Preparation of polycyclic compounds by intramolecular 1,3-dipolar cycloaddition of carbonyl ylides to alkenes 11301].

Schreiber and co-workers (436) prepared a library calculated to contain 2.18 million polycyclic compounds through the 1,3-dipolar cycloaddition of a number of nitrones with alkenes supported on TentaGel S NH2 resin (Scheme 1.83). (—)-Shikimic acid was converted into the polymer bound epoxycyclohexenol carboxylic acid 376 (or its enantiomer), coupled to the resin via a photolabile linker developed by Geysen and co-workers (437) to allow release of the products from the resin in the presence of live cells by ultraviolet (UV)-irradiation. A range of iodoaromatic nitrones (377) was then reacted with the ot,p-unsaturation of the polymer-bound amide in the presence of an organotin catalyst, using the tandem esterification/ dipolar cycloaddition methodology developed by Tamura et al. (84,85) Simultaneous cyclization by PyBrop-mediated condensation of the acid with the alcohol... 

It should be emphasized that in some cases the insertions take place several times sequentially. For example, in carbonylation, the insertion of alkene is followed by CO insertion. Sometimes, further insertions of another alkene and CO take place. Particularly useful is the formation of polycyclic compounds by intramolecular sequential insertions of alkenyl and alkynyl bonds. 

We also discuss the conformations of cycloalkanes, especially cyclohexane, in detail because of their importance to the chemistry of many kinds of naturally occurring organic compounds. Some attention also will be paid to polycyclic compounds, substances with more than one ring, and to cyclo-alkenes and cycloalkynes. 

Intramolecular photocycloaddition of alkenes to benzene rings is a synthetically useful method for the construction of polycyclic compounds including natural products [23,25], In 1969, Morrison and Ferree reported the first example of intramolecular 1,3-photocycloaddition of m-6-phenylhex-2-ene (156) [228,229] (Scheme 51). 

Polycyclic compounds are prepared by domino insertions of alkenes and alkynes to the allenylpalladium intermediates. As examples, 1,6-enyne 28 underwent intramo-... 

The intramolecular version presents a very useful synthetic route to various polycyclic compounds. Even terminal alkenes give cyclopentenones in good yields, assisted by the addition of /V-methylmorpholine N-oxide (NMO) [85], The addition of trimethylamine A -oxidc also dramatically accelerates the reaction in the presence of oxygen, and both inter- and intramolecular reactions proceed at 0°C to room temperature [86]. The reaction was found to proceed rapidly at 25 °C by the addition of aqueous NH4OH [87]. Numerous applications to natural product syntheses have been reported. The tri- and tetracyclic skeletons 214 for crinipellin B, from 213 [88], and the triquinacene derivative 216, from 215, have been constructed [89,90], These results show that internal alkynes and terminal alkenes react smoothly in the intramolecular reactions. Domino reaction of the endiyne 217 produced the strained molecule of oxa[5.5.5.5]fenestrenedione (219) via 218 [91]. 

C(2)-C(3) fused polycyclic cephalosporins have received considerable attention as new candidates for /3-lactam antibiotics. An access to tricyclic cephalosporins based on metal-promoted alkenylation of 3-trifloxy-A3-cephem and subsequent Diels-Alder reaction has been published <1996TL5967>. Alternatively, the reaction of a cephalosporin triflate with silyl enol ethers and silylketene acetals has been described to afford tri- and tetracyclic cephalosporins <1996TL7549>. A related process is the formation of fused polycyclic cephalosporins 27 and 28 bearing a wide range of functionalities from the reaction of cephalosporin triflates 26 with unsaturated compounds (alkenes and alkynes) and a base (Scheme 5) <1997JOC4998>. These studies have suggested that the reaction proceeds via the intermediacy of a six-membered cyclic allene which undergoes concerted nZs + K2a cycloaddition with alkenes and acetylenes. 

Indolylacyl radicals are extremely useful reactive intermediates that participate in inter-and intramolecular reactions with alkenes and (hetero)aromatic systems. This radical methodology gives easy access to a wide range of indolic structures, including simple indolyl ketones as well as more complex polycyclic compounds embodying the 2-acylindole moiety. 

An interesting example of an intramolecular 1,3-dipolar cycloaddition of an isomunchnone with an unactivated alkene to produce a complex polycyclic compound in one step has been reported <89TL4077 89CB1081>. The isomunchnones derived from the Rh2(OAc)4 catalyzed reaction of acyclic diazoimides 92-96 were found to undergo facile cycloaddition onto the tethered it-bond to provide polycyclic adducts 97-101. A notable feature of this cycloaddition is that only one diastereomer is formed. The relative... 

Tandem pericyclic reactions are a powerful strategy for construction of complex, polycyclic compounds. In recent years tandem [4 + 2]/[3 + 2] chemistry of nitro-alkenes and nitronates has been developed by Denmark et al. as a general approach to functionalized pyrrolidine-containing structures [118]. Within the subclass of inter [4 -I- 2]/intra [3 + 2] cycloadditions, they have documented the fused mode (/3-tether, Eq. 77), spiro mode (a-tether, Eq. 78), and bridged mode (a-tether, Eq. 79 or /3-tether, Eq. 80) constructions. These are highly stereoselective processes in the presence of Lewis acid such as SnCU and are amenable to asymmetric modification by use of chiral vinyl ethers. Finally, the nitroso acetals are readily transformed, by hydroge-nolysis, into polycyclic, a-hydroxypyrrolidinones, 4-aminocyclohexanones, and cyclo-pentylamines. 

Pinacol rearrangement, 292, 299, 309, 326 Piperidine, 455 Planck s constant, 231 Plane of symmetry, 69 Polar bonds. 27 Polarity, 21 Polarizability, 121 Polar molecules, 27 Polycyclic compounds, 162 Polygon rule, 197 Polymerization, alkenes, 102 116 dienes, 153//... 

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