1.3- dipolar cycloadditions intramolecular

The reaction is illustrated by the intramolecular cycloaddition of the nitrilimine (374) with the alkenic double bond separated from the dipole by three methylene units. The nitrilimine (374) was generated photochemically from the corresponding tetrazole (373) and the pyrrolidino[l,2-6]pyrazoline (375) was obtained in high yield 82JOC4256). Applications of a variety of these reactions will be found in Chapter 4.36. Other aspects of intramolecular 1,3-dipolar cycloadditions leading to complex, fused systems, especially when the 1,3-dipole and the dipolarophile are substituted into a benzene ring in the ortho positions, have been described (76AG(E)123). 

Hart and Brewbaker have described the cyclization of l,3-bis(diazopropane) to pyrazole (Scheme 49) by a concerted, intramolecular 1,3-dipolar cycloaddition (69JA711). 

When the chain between the azirine ring and the alkene end is extended to three carbon atoms, the normal mode of 1,3-intramolecular dipolar cycloaddition occurs. For example, irradiation of azirine (73) gives A -pyrroline (74) in quantitative yield 77JA1871). In this case the methylene chain is sufficiently long to allow the dipole and alkenic portions to approach each other in parallel planes. 

The phenylhydrazones of 2-[(2-alkenyl)amino]-3-formyl-4//-pyrido-[1,2-n]pyrimidin-4-ones 242 underwent a thermally induced intramolecular 1,3-dipolar cycloaddition leading to a mixture of tetracyclic compounds 243 and 244 at room temperature or to 244 under reflux (96T901). Derivatives 243 were not stable and converted to compounds 244 gradually on standing or on heating their ethanolic solutions in air. The ( )-hydrazones 245 could be isolated only in the case of... 

The importance of the 1,3-dipolar cycloaddition reaction for the synthesis of five-membered heterocycles arises from the many possible dipole/dipolarophile combinations. Five-membered heterocycles are often found as structural subunits of natural products. Furthermore an intramolecular variant makes possible the formation of more complex structures from relatively simple starting materials. For example the tricyclic compound 10 is formed from 9 by an intramolecular cycloaddition in 80% yield ... 

The intramolecular cycloaddition of a nitrile oxide (a 1,3-dipole) to an alkene is ideally suited for the regio- and stereocontrolled synthesis of fused polycyclic isoxazolines.16 The simultaneous creation of two new rings and the synthetic versatility of the isoxa-zoline substructure contribute significantly to the popularity of this cycloaddition process in organic synthesis. In spite of its high degree of functionalization, aldoxime 32 was regarded as a viable substrate for an intramolecular 1,3-dipolar cycloaddition reaction. Indeed, treatment of 32 (see Scheme 17) with sodium hypochlorite... 

The only examples of fully unsaturated tetrazoloazepines, e.g. 3, have been prepared by an unusual and intriguing reaction involving the action of azide ion on 4,7-disulfonylbenzofurazan 1-oxides, e.g. I.148 A mechanistic rationale involving intramolecular 1,3-dipolar cycloaddition of an azidonitrile intermediate, e.g. 2, has been proposed. 

Treatment of 2- 5//-dibenz[i>,/]azepin-5-yl acetaldehyde (16), prepared in 68% yield by /V-alkylation of 5/7-dibenz[A,/]azepine with bromoacetaldehyde diethyl acetal followed by acid hydrolysis, with methyl hydroxylamine yields the isolable nitrone 17, which in refluxing toluene undergoes intramolecular 1,3-dipolar cycloaddition at the CIO —Cl 1 alkene bond to give 2,3,3a, 12b-tetrahydro-2-methyl-3,8-methano-8//-dibenz[i>,/]isoxazolo[4,5-r/]azepine (18).235... 

Intramolecular and intermolecular 1,3-dipolar cycloadditions of aziridine-2-car-boxylic esters with alkenes and alkynes have been investigated [131, 132]. Upon heating, aziridine-2-carboxylates undergo C-2-C-3 bond cleavage to form azome-... 

Another example of a microwave-assisted 1,3-dipolar cycloaddition using azomethine ylides and a dipolarophile was the intramolecular reaction reported for the synthesis of hexahydrochromeno[4,3-fo]pyrrolidine 105 [70]. It was the first example of a solvent-free microwave-assisted intramoleciflar 1,3-dipolar cycloaddition of azomethine ylides, obtained from aromatic aldehyde 102 and IM-substituted glycinate 103 (Scheme 36). The dipole was generated in situ (independently from the presence of a base like TEA) and reacted directly with the dipolarophile present within the same molecifle. The intramolecu-... 

Figure 6.54 A domino DKR-intramolecular 1,3-dipolar cycloaddition reaction.

Nakayama J, Sugihara Y (1999) Chemistry of Thiophene 1,1-Dioxides. 205 131-195 Namboothiri INN, Hassner A (2001) Stereoselective Intramolecular 1,3-Dipolar Cycloadditions. 216 1-49... 

The pyrimidines 62 undergo cyclisation on refluxing in dioxane to yield not only the pyrazolopyrimidines 63, but the novel pyrazolo[3, 4 4,5]pyrido[2,3-rflpyrimidines 64 by an intramolecular 1,3-dipolar cycloaddition reaction (Scheme 9)<96JCS(P1)1999>. 

Keywords Intramolecular 1,3-dipolar cycloadditions. Stereoselectivity, Nitrile oxides, SUyl nitronates. Oximes, H-Nitrones, Azides, NitrUimines... 

This review covers primarily the results of intramolecular 1,3-dipolar cycloadditions reported by us in the past 15 years in perspective to closely related work by others. 

The reaction of the a-bromo aldoxime 52e (R = R = Me) with unsaturated alcohols has been extended to the heterocyclic systems furfuryl alcohols and 2-thiophene methanol [29b]. The furanyl and thiophenyl oximes 63a-c were treated with NaOCl and the resulting heterocyclic nitrile oxides were found to undergo spontaneous intramolecular dipolar cycloaddition to produce the unsaturated tricyclic isoxazolines 64a-c in high yield (Eq. 5). In these cases, the heterocyclic ring acts as the dipolarophile with one of the double bonds adding to the nitrile oxide [30]. 

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