Heterocycles oxidative cleavage

In recent years a number of new isoquinoline alkaloids of untypical structures, i.e., structures with open heterocyclic rings, have been isolated from natural sources. These bases were named secoisoquinoline alkaloids because they were believed to be produced in vivo from classic isoquinoline alkaloids as a result of various degradation processes causing oxidative cleavage of some bonds. 

The conversion of the polystyrene-supported selenyl bromide 289 into the corresponding acid 290 allowed dicyclohexylcarbodiimide (DCC)-mediated coupling with an amidoxime to give the 1,2,4-oxadiazolyl-substituted selenium resin 291 (Scheme 48). Reaction with lithium diisopropylamide (LDA) and allylation gave the a-sub-stituted selenium resin 292, which was then used as an alkene substrate for 1,3-dipolar cycloaddition with nitrile oxides. Cleavage of heterocycles 293 from the resin was executed in an elegant manner via selenoxide syn-elimination from the resin <2005JC0726>. 

A rapid access to carbocyclic nucleosides, containing a fused isoxazoline ring has been proposed, starting from cyclopentadiene. The route involves a het-ero Diels-Alder cycloaddition reaction of nitrosocarbonylbenzene followed by a 1,3-dipolar cycloaddition of nitrile oxides, cleavage of the N-0 tether and transformation of the heterocyclic aminols into nucleosides via construction of purine and pyrimidine heterocycles (457). 

The ready alkylation of heterocyclic thiols lends this link to applications in solid-phase synthesis. Although much more work has been done in other heterocyclic systems, a prototype solid-phase synthesis has been described in which the pteridine is built from a 2- or 4-alkylthiopyrimidine attached to a cross-linked polystyrene support <20030BG1909, 2003TL1267> Oxidative cleavage was preferred using DMDO to avoid unwanted by-products... 

An alternative furan-based jasmone synthesis has been accomplished through oxidative cleavage of this heterocyclic ring (73AJC2671). Thus, the furan (85) was oxidized with Collins reagent to the enedione (86) and the conjugated double bond reduced with sodium dithionite. Base cyclization then gave pure (Z)-jasmone (Scheme 21). 

S. Hanessian and R. Ldger, Expedient assembly of carbocyclic, heterocyclic, and polycyclic compounds by Me3Sn radical mediated carbocyclizations of dienes and trienes A novel oxidative cleavage of the C-Sn bond, J. Am. Chem. Soc. 7)4 3115 (1992). 

A solid-phase Ugi-Reissert reaction on chloroformate resin, has been reported. The product, the ot-carbamoylated isoquinoline 230, is released by oxidative cleavage (Scheme 33a). Interestingly, the enamide moiety in the adduct can be exploited to perform this process in tandem with a Povarov MCR [189, 190]. In this way, by interaction of dihydroisoquinoline 231 with aldehydes, anilines and a suitable Lewis acid catalyst, the polyheterocyclic system 232 was prepared (Scheme 33b). The Zhu group devised an innovative approach for the synthesis of this class of compounds. They employed the heterocyclic amine 233, which was oxidized in situ to the dihydroisoquinoline 234 with IBX, to undergo the classic Ugi reaction. Remarkably, all the components are chemically compatible, allowing the sequence to proceed as a true MCR (Scheme 33c) [191]. 

The majority of reported reactions of aryl and heteroaryl substrates with organocopper reagents are examples of Stephens-Castro coupling or the more recent catalytic version of that reaction. The reaction has found recent application in syntheses of C-(6)-substituted pterins and pteridines, substituted pyridines, and the antitumor antibiotic fredericamycin A," to name a few. Aryl iodide can be che-mospecifically displaced in the presence of bromide," and 2,5-dibromopyridine is regioselectively substituted at the 2-position. Substitution of halobenzenes by propargyl alcohol, followed by oxidative cleavage, provides a convenient route to terminal arylalkynes. " Fused heterocycles are formed in reactions of aryl halides bearing nucleophilic ortho substituents. - "... 

When the donor character of the amino substituent at the transition-metal-carbene carbon atom is reduced, it should be possible to influence the thermal stability and reactivity in favor of the desired cyclopropanation process. Indeed, pyrrol-1 -ylcarbene complexes 18 of chromium, molybdenum and tungsten do exhibit the desired reactivity. In the last step, the pyrrole ring of 19 can be converted to the NH2 function in 20 after oxidative cleavage with ozone.In this respect, the pyrrole heterocycle represents a synthetic equivalent of the amino function. 

There are many reactions that result in the conversion of dihydrothiazines into other heterocycles. They may be divided into three categories those that involve a nonoxidative and nonreductive cleavage, those that require an oxidative cleavage, and those that proceed by a reductive cleavage of the dihydrothiazine ring. 

The bacterial degradation of quinoline heterocycles proceeds via oxidation to 3-hydroxy-4-oxoquinolines, which are substrates for a novel family of dioxygenases. The reaction is similar to the copper-dependent quercetin dioxygenase (see Section 8.16.4.2), involving oxidative cleavage of two C—C bonds, and liberation of carbon monoxide however, remarkably, these enzymes have no cofactor requirement. Two dioxygenases QDO... 

Oxidative cleavage of fused heterocyclic ring systems... 

Oxidative cleavage of fused heterocyclic systems is often of preparative value. The benzene ring of quinoline, for instance, can be oxidized away,... 

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