Ring systems alkenylation

Representatives of the pyrrolo[3,2-/][l,7]naphthyridine ring system, viz. 61, have been obtained by palladium-catalyzed cyclization of the corresponding 5-alkenyl-6-amino[l,7]naphthyridines (Scheme 19) <2002H(56)443>, although this reaction appears not to be general and its scope is as yet undefined. 

Reggelin et al. reported the application of methylated, enantiomerically pure acyclic and cyclic 2-alkenyl sulfoximines 203 for the synthesis of highly substituted aza(poly)cyclic ring systems 204 under complete stereocontrol <06JA4023 06S2224>. 

Gilchrist examined the cyclization of Af-alkenyl-2-iodoindoles with palladium [268, 269], For example, reaction of A-pentenylindole 244 under Heck conditions affords a mixture of 245 and 246 in very good yield. In the absence of TIOAc, 246 is the major product. Further exposure of 245 to Pd(OAc)2 gives 246. Reaction of l-(4-butenyl)-2-iodoindole under similar conditions affords the pyrrolo[l,2-a]indole ring system in modest yield (35%). 

Intramolecular 3 - - 2-photocycloadditions of alkenyl methyl 1,4-naphthalenedicarb-oxylates (39) yield 3- -2-cycloadducts (40) having 9-11-membered ring systems in addition to the characteristic flve-membered ring structure (Scheme 13). ... 

The palladium catalysed sequential alkylation-alkenylation of 5-iodoquinoline leads to the formation of the quinolooxepin ring system (5.20.), The process, closely related to the Catellani reaction,19 runs through an ort/zo-alkylation - Heck reaction sequence. The preparation of a series of benzoxepines has also been achieved in this manner, starting from such iodobenzene derivatives, where one of the or/7 o-positions was blocked by substitution.20... 

A classical method for controlling the stereoselectivity of intramolecular nitrone cycloadditions is to have a chiral center located on the chain between the nitrone and the alkene moiety (175-222). In a few other cases, the chirality is located outside the formed ring system (223-229). Marcus et al. (230) recently described an intramolecular 1,3-dipolar cycloadditions of the 5-alkenyl- and 6-alkenylnitrones 124 and 127 (Schemes 12.42 and 12.43). The chiral starting material 123 was obtained in 97% ee from an enzymatic cyanohydrin formation. Subsequent... 

In an oxidative addition, Pd(0) complex 22 with BINAP as a ligand accepts alkenyl triflate It. The resulting Pd complex 23 is cationic, since the triflate anion is bound only loosely to the palladium and dissociates from the complex.1 Syn insertion of one of the two enantiotopic double bonds of the cyclopentadienc into the alkenyl-Pd bond of complex 23 leads firs to q -allyl-Pd complex 24. This is in rapid equilibrium with t 3-allyl-Pd complex 25. Neither 24 nor 25 contains a p-H atom in a yn relationship to palladium. Moreover, internal rotation is impossible in the con form a-tionaily fixed ring system. For this reason there is no possibility of a subsequent p-hydride elimination that would once again release the palladium catalyst. In a normal Heck reaction (see discussion) the catalytic cycle would be broken at this point. 

The copper complexed aminyl radical cyclization has been used as a key step in a short total synthesis of ( )-gephyrotoxin 223AB (60). The alkenyl substituted ALchloropiperidine 59 was stereoselectively cyclized to construct the indolizidine ring system (Scheme 17) (86JOC5043). Tribu-... 

The stereoselective intramolecular Diels-Alder reaction of 3-alkenyl(oxy)-2(l//)-pyrazinones leading to tricyclic ring systems was investigated <02TL447>. A one-pot 7-alkoxylation of 6-arylpyrazino[2,3-c][l,2,6]thiadiazine 2,2-dioxides 169 was accomplished by using N-halosuccinimides <02EJ02109>, and the nitration of 2-(5-methyl-2-furyl)quinoxaline was shown... 

Sml2-mediated radical cyclisations involving alkyl, alkenyl and aryl radical intermediates can be used to construct efficiently five-membered and, in certain cases, six-membered ring systems. This approach provides a useful alternative to trialkyltin hydride-mediated methods as toxic reagents and problematic tin byproducts are avoided. In addition, the use of Sml2 to induce radical cyclisations has led to the development of a number of powerful, radical/anionic sequential processes for the construction of complex systems. Sequential reactions involving radical-alkene/alkyne cyclisations are discussed in Chapter 6. 

Similar methodology was employed to the synthesis of more complex polycyclic ring system, as shown in Scheme 32 <1997TL9069>. The initial alkenyl radical 54, formed by an intramolecular radical 13-< 4t>-dig macro-cyclization, initiated a radical cascade reaction by first reacting at the a-position of the furan ring. 

A BINAP-Pd complex catalyzes a highly enantioselective C-C bond formation between an aryl triflate and 2,3-dihydrofuran (eq 22). The intramolecular version of the reaction using an alkenyl iodide in the presence of PdCl2[(/J)-BINAP] and Silver(I) Phosphate allows enantioselective formation of a bicyclic ring system (eq 23). ... 

In other studies, various complex ring systems useful in the synthesis of natural products have been prepared by anodic oxidation of electron-rich phenols bearing alkenyl side chains of varying substitution and stereochemistry [59-65]. In some instances, the... 

A substrate with the C-C double bond of the 6-alkenyl substituent situated one carbon atom further out from the bicyclohexanone ring system was also examined. The best Lewis acid catalyst was found to be acetyl methanesulfonate which led to the formation of cedrone (17) and epicedrone (18). ... 

Nucleophilic addition to organic radical-cations is one of the most common pathways to produce radicals. Irradiation of a wide variety of A-(2-alkenyl)- and N-(3-alkenyl)phthalimides and A-alkenylphthalimides [26] with a remote alkenyl double bond [27] afford new 5-, 6- and medium-size ring systems. Irradiation in methanol-acetonitrile triggers intramolecular electron transfer from the olefin double bond to the excited phthalimide carbonyl group. Because of the highly nucleophilic character of methanol, the olefin radical-cation can be trapped. The derived radical combines with the radical-anion to yield coupling products (Scheme 15). 

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