Cycloaddition 1,3-dipoIar

An in depth account of intramolecular 1,3-dipoIar cycloadditions involving dipoles such as nitrUe oxides, sUyl nitronates, H-nitrones, azides, and nitrUimines is presented with particular emphasis on the stereochemistry during the cycloaddition. Various methods employed for the generation of the dipoles and their applications to stereoselective synthesis are also discussed. 

Heterocyclics of all sizes, as long as they are unsaturated, can serve as dipolarophiles and add to external 1,3-dipoles. Examples involving small rings are not numerous. Thiirene oxides add 1,3-dipoles, such as diazomethane, with subsequent loss of the sulfur moiety (Section 5.06.3.8). As one would expect, unsaturated large heterocyclics readily provide the two-atom component for 1,3-dipoIar cycloadditions. Examples are found in the monograph chapters, such as those on azepines and thiepines (Sections 5.16.3.8.1 and 5.17.2.4.4). 

The most important method for the synthesis of 3i/-pyrazoles is by 1,3-dipoIar cycloaddition between a diazo compound and an alkyne, although alkenes bearing suitable leaving groups have also been used. Other methods include the cyclization of vinyldiazo compounds, and the oxidation of pyrazolines. 

The mechanism of the reaction has generally been discussed in terms of a thermally allowed concerted 1,3-dipoIar cycloaddition process, in which control is realized by interaction between the highest occupied molecular orbital (HOMO) of the dipole (diazoalkane) and the lowest unoccupied molecular orbital (LUMO) of the dipolarophile (alkyne).76 In some cases unequal bond formation has been indicated in the transition state, giving a degree of charge separation. Compelling evidence has also been presented for a two-step diradical mechanism for the cycloaddition77 but this issue has yet to be resolved. 

A synthesis of l-oxo-l//-2,3-benzopyrrolizines (129a), using a 1,3-dipoIar cycloaddition, has been reported.79 A series of isatins (121) on treatment with acetic anhydride formed mesoionic intermediates (128), which underwent 1,3-dipolar cycloaddition in situ with dimethyl acetylenedicarboxylate to give... 

First step is a 1,3-dipoIar cycloaddition of ozone to the alkene leading to the primary ozonide (molozonide, 1,2,3-trioxolane, or Criegee intermediate) which decomposes to give a carbonyl oxide and a carbonyl compound ... 

Polymerizable indazole derivatives have received some attention with respect to the preparation of redox polymers and metal ion chelating polymers (73MI11102). Monomers such as 3-vinyl-4,7-dihydro-l//-4,7-indazoledione (63) are readily prepared by 1,3-dipoIar cycloaddition of vinyldiazomethane to 1,4-benzoquinones. Crosslinked, low swelling, recyclable redox polymers have been prepared from these monomers. 

MH A. Padwa, 1,3-DipoIar Cycloaddition Chemistry, Vols. I and 2. Wiley,... 

RING FORMATION VIA CYCLOADDITION REACTIONS 4.03.6.1 1,3-DipoIar Cycloadditions... 

For example, Bazureau has used this approach to prepare imidazolium ions with appended carboxylic acid groups, which have been used as replacements for sohd polymer supports in the heterogeneous phase synthesis of small organic molecules via Knoevenagel and 1, 3-dipoIar cycloaddition reactions [12]. 

The cycloadducts have been transformed into pyrrolidines by reductive ring contraction. However, cycloadducts bearing a suitable alkene functionality in the side chain usually undergo [3+2] cycloaddition upon warming to room temperature. Inter- and intramolecular combinations of hetero Diels-AIder reactions with 1,3-dipoIar cycloadditions of the resulting nitrone have been intensively studied, developed and have been recently reviewed by Denmark et al. ... 

This compound—known as an ozonide—is the first stabie product of the reaction with ozone. It is the culmination of two 1,3-dipoiar cycloadditions and one reverse 1,3-dipolar cycloaddition. It is still not that stable and is quite explosive, so for the reaction to be of any use it needs decomposing. The way this is usuaiiy done is with dimethylsulfide or PhsP, which attacks the ozonide to give DMSO and two moiecules of aldehyde. 

DipoIar cycloadditions of fiiUerenes gave expected products. In cycloadditions with azides triazolines 25 were formed, while with diazo compounds such as 9-diazofluorene 22, spiro cyclopropane products 24 were directly prepared. In this case initially formed pyrazoline intermediate 23 was not isolated (Scheme 7.6) [13]. 

Synthesis.—PechmanrCs Synthesis. The 1,3-dipoIar cycloaddition of diphenyl(or methyl)phosphinic isothiocyanates to diazomethane or phenyl-diazomethane affords low yields (7—29%) of the appropriate substituted 1,2,3-thiadiazoles (5). The method is an extension of Pechmann s old-established synthesis (see Volume 1, p. 444). 

Photoinduced 1,3-Dipoiar Cycloaddition Reaction Between Tetrazoles... 

The in situ generation of nitrile oxides 119 and subsequent intra- or intermolecular 1,3-dipoIar cycloaddition reactions with alkenes and alkynes represent one of the most exploited strategies for the preparation of diverse isoxazoline 121 and isoxazole 120 derivatives. Ciufolini et al. [89] reported that PIDA in combination with a substoichiometric amount of TFA efficiently oxidize aldoximes 118 to nitrile oxides 119, which were trapped in situ with olefins to afford... 

Scheme 6.16 1,3-DipoIar cycloadditions of azomethine ylide to nitroalkenes.

Besides, Prato and coworkers have reported that CNTs underwent 1,3-dipoIar cycloaddition when heated in DMF in the presence of a-amino acid and aldehyde. This reaction provides a versatile and powerful approach to attach different functionalities to CNTs and these functional groups can be further coupled with amino acids and bioactive peptides. It has been demonstrated that some of the peptide-functionalized CNTs can enhance the immunization to virus-specific neutralizing antibody responses. ... 

Reduced Pyrazoles and Imidazoles. l-Aryl-4,5- and 5,5-diamino-4,5-dihydropyra-zoles have been prepared in high yield by the 1,3-dipoIar cycloaddition of nitrile imines with 1,2- and 1,1-diaminoethenes (Scheme 78). ... 

The Rh2(OAc)4-catalyzed decomposition of 3-diazo-2,4-chromenedione in the presence of terminal alkynes has also been described. In this case, the reactions led to separable mixtures of the corresponding 2-substituted furo[3,2-c] coumarins 31 and their linear isomers 32, resulting from the nonregioselective 1,3-dipoIar cycloaddition of the in situ formed a,a"-dicarbonyI carbene with the C=C bond of the alkyne (Scheme 13) [81]. 

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