1.3- Dipolar cycloaddition of nitrile imines

The silver acetate-promoted 1,3-dipolar cycloaddition of nitrilimines with 3(/f )-pheny]-4(A )-cinnamoyl-2-azetidinone produced the major adduct, 4-(4,5-dihydro- (g) pyrazol-5-yl)carbonyl-2-azetidinones, with high stereoselectivity.70 The 1,3-dipolar cycloadditions of substituted 2,7-dime(liyl-3-thioxo-3,4,5,6-ici.rahydro-2//- 1,2,41 triazepin-5-one with iV-aryl-C-ethoxycarbonylnitrilimines are highly chemoselective, where the sulfur atom of the dipolarophile interacts with the carbon atom of the dipole.71 The enantioselective 1,3-dipolar cycloaddition of nitrile imines with electron deficient acceptors produces dihydropyrazoles in the presence of 10 mol% of chiral Lewis acid catalyst.72... 

Dipolar Cycloaddition of Nitrile Imine and Azomethine Imines/or Ylides... 

Dipolar cycloadditions of nitrile imines under the action of microwave irradiation have rarely been described. Under classical conditions these reactions are nor-... 

Dipolar cycloadditions of nitrile imines with alkenes lead to 2-pyrazolines. Moderate select vities are observed in reactions with the acrylate of (/ )-pantolactone. 

Recently, this catalytic system was further applied in an enantioselective 1,3-dipolar cycloaddition of nitrile imines 47 with methylene indolinones 26. Stanley et al. prepared the 39c-Mg(NTfa)2 catalyst and used 10 mol% of it to promote the process, providing the corresponding adducts 48 in 63-91% pelds and with 61-99% enantiomeric excess (Scheme 3.14). ... 

SCHEME 5.46 1,3-dipolar cycloaddition of nitrile imines with S3fmmetrical alkenes or alkynes. 

Poly(ethylene glycol) supported liquid-phase syntheses by both the reaction of (polyethylene glycol (PEG))-supported imines with nitrile oxides, generated in situ from aldoximes, (300) and 1,3-dipolar cycloadditions of nitrile oxide, generated in situ on soluble polymers with a variety of imines (301, 302) have been described. The solid-phase synthesis of 1,2,4-oxadiazolines via cycloaddition of nitrile oxide generated in situ on solid support with imines has also been elaborated (303). These syntheses of 1,2,4-oxadiazolines provide a library of 1,2,4-oxadiazolines in good yields and purity. 

Dipolar cycloadditions of nitrile oxides " and nitrile imines " " with dehydroamino acid derivatives have also been described. 

The reaction of nitrile oxides with 4-arylmethylene-5(4//)-oxazolones 675 to give the corresponding spiroisoxazoline oxazolones 676 is also well known.The regiochemistry of this cycloaddition reaction was initially incorrectly assigned but a careful study of the reaction showed that the regiochemistry of the 1,3-dipolar cycloaddition of nitrile oxides is the same as that observed with nitrile imines (Scheme 7.213). Examples of spiroisoxazoline oxazolones are shown in Table 7.49 (Fig. 7.60). 

To produce a 1,2-azole, a 1,3-dicarbonyl-compound needs to be condensed with a unit providing the two heteroatoms - a hydrazine or hydroxylamine. The 1,3-dipolar cycloaddition of nitrile oxides or nitrile imines to alkynes provides an important route to isoxazoles and pyrazoles. 

A highly regio- and diastereoselective 1,3-dipolar cycloaddition of nitrile oxides to the imine groups in 2,4-dimethyl-3//-l,5-benzodiazepines to afford bis[l,2,4-oxadiazolo[l,5]benzodiazepine] adducts has been reported by Baouid and co-workers stereochemical features were confirmed by single crystal X-ray crystallography on one of the adducts <04SC3565>. 

Sol 2. (b) It is an example of a widely used masked-aldol reaction. 1,3-Dipolar cycloaddition of nitrile oxides with an alkene (or alkyne) gives a cyclic product, isoxazoline (or isoxazole). These cyclic compounds are readily cleaved by reduction of the N—O bond and subsequent hydrolysis of the resulting imine to give aldol-type p-hydroxycarbonyl (or Claisen-type P-dicarbonyl) products. 

Dipolar cycloaddition of azomethine imine or nitrile imine-type dipoles with alkenes or alkynes yields nitrogen heterocycles containing two nitrogen atoms in the ring. MeOPEG resin was applied in the solid-phase synthesis of pyrazolines (Scheme 11.13). Resin-bound... 

Traceless cleavage of products from the resin can be achieved through an elimination reaction. Aromatization of the product can be the driving force for the elimination. Piperazine resin-bound enamine reacted regioselectively in a 1,3-dipolar cycloaddition with nitrile imines generated in situ (Scheme 11.16). Elimination of the piperazine linker with highly diluted trifluoroacetic acid gave diverse 1,4-diarylpyrazoles in a traceless manner. 

Asymmetric 1,3-dipolar cycloadditions of nitrile oxides, nitrones, and azomethine imines were developed by the design of a novel chiral system possessing two- or three-metal centers utilizing tartaric acid ester as a chiral auxiliary. The strategy was applied to asymmetric hetero Diels-Alder reaction of... 

Some new spirothiadiazolepyrazolo[l, 4-e/][1,5] benzodiazepines have been reported by Rakilo et al. They are prepared by a regioselective 1,3-dipolar cycloaddition of a nitrile imine with pyrazolo[l,5,4-e/][ 1,5]benzodiazepine-thione <00H(53)571>. 

I.3.4.2. Intermolecular Cycloaddition at C=X or X=Y Bonds Cycloaddition reactions of nitrile oxides to double bonds containing heteroatoms are well documented. In particular, there are several reviews concerning problems both of general (289) and individual aspects. They cover reactions of nitrile oxides with cumulene structures (290), stereo- and regiocontrol of 1,3-dipolar cycloadditions of imines and nitrile oxides by metal ions (291), cycloaddition reactions of o-benzoquinones (292, 293) and aromatic seleno aldehydes as dipolarophiles in reactions with nitrile oxides (294). 

A series of pyrazolino[60]fullerenes has been prepared in one-pot reactions by 1,3-dipolar cycloaddition of the corresponding nitrile imines [306-311]. In all cases... 

The 1,3-dipolar cycloaddition of pyridine N -unsubstituted N-imines with activated dipolarophiles such as acetylenic esters,58,120,182,184 ketones,185 and nitriles,186 ethyl acetoacetate,154,159 acetylacetone (Section IV.A.6.),154 /J-haloacrylates,54,159 and nitriles138 provides particularly facile entries to many pyrazolo[l,5-a]pyridines and triazolo[l,5-a]pyridines (Eq. 28). 

The synthetic approach used to prepare isoindazolylpyrazolino[60]fullerenes 50a-c (Scheme 21.18), in 21-27% isolated yield [56], relies on 1,3-dipolar cycloaddition of the isoindazolyl nitrile imines under the action of microwave irradiation. The nitrile imines can be generated in situ from the corresponding isoindazole hy-drazones (49a-c), which in turn are synthesized from the respective aldehydes [57] (47a-c). 

The asymmetric 1,3-dipolar cycloaddition of C,A(-cyclic azomethine imines with unsaturated nitriles yielded chiral cyanopyrazolidines in good to excellent yields and... 

SCHEME 6 1,3-dipolar cycloaddition of in situ-generated nitrile imines and aryne [26]. 

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