Nitrile imines, 1,3-dipolar cycloaddition

Dipolar cycloaddition reactions with azides, imines, and nitrile oxides afford synthetic routes to nitrogen-containing heterocycles (25—30). 

A second category of silene reactions involves interactions with tt-bonded reagents which may include homonuclear species such as 1,3-dienes, alkynes, alkenes, and azo compounds as well as heteronuclear reagents such as carbonyl compounds, imines, and nitriles. Four modes of reaction have been observed nominal [2 + 2] cycloaddition (thermally forbidden on the basis of orbital symmetry considerations), [2 + 4] cycloadditions accompanied in some cases by the products of apparent ene reactions (both thermally allowed), and some cases of (allowed) 1,3-dipolar cycloadditions. 

From the 1,3-dipolar cycloaddition of nitrile oxides to azomethines (imines) 291... 

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). 

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. 

Some features are characteristic of reactions of nitrile oxides with 2,4,6-cyclo-hep tatrien-l-imines (8-azaheptafulvenes). 1,3-Dipolar cycloaddition to the C=N double bond of N-aryl-2,4,6-cycloheptatrien-l-imines 142 (R = Ar), affording... 

N-benzyladamantyl-2-imines, and 2-methyleneadamantanes were studied (352, 353). In particular, X-ray single-crystal analysis confirmed the configuration of the oxathiazoline 185, resulting from the favored attack of nitrile oxide on the 5-fluoroadamantane-2-thione. 2-Silyl-substituted oxathiazole 186 was synthesized by the 1,3-dipolar cycloaddition reaction of phenyl triphenylsilyl thioketone with 4-chlorobenzonitrile oxide (354). 

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... 

P. Caramella and P. Griinanger, Nitrile Oxides and Imines in 1,3-Dipolar Cycloaddition Chemistry, A. Padwa, ed., Wiley, New York, 1984, pp. 291-393. 

The chiral acrylate 164 was used in a 1,3-dipolar cycloaddition with a nitrile imine. Bis(trityl)nitrile imine was found to undergo a diastereoselective 1,3-dipolar cycloaddition with (f )-a-(acyloxy)-p,p-dimethyl-y-butyrolactone 164 to give the 2-pyrazoline product with a de of 50% (Scheme 12.51) (275). 

Karlsson and Hogberg (291,292) applied the thiocarbonyl ylide 175 in a diastereoselective 1,3-dipolar cycloaddition with 165. The thiocarbonyl yhde was generated in situ by an elimination reaction. The reaction with 165 gave 176 (R = Bu, BnO, Ph) with selectivities of up to 64—80% de. Furthermore, the cycloaddition of a chiral galactose-derived nitrile imine with 165 has been reported (104). 

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

TABLE 7.48. OXAZOLONE SPIROPYRAZOLINES FROM 1,3-DIPOLAR CYCLOADDITION REACTION OF UNSATURATED 5(4//)-OXAZOLONES WITH NITRILE IMINES ... 

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). 

Cyclobut[f]thiophene is a poor dipolarophile and requires prolonged reaction times to produce the 1,3-dipolar cycloaddition product 84 on reaction with diazomethane (Equation 44) <1999J(P1)605>. Reactions with nitrile imines or azomethine imines fail to provide cycloadducts. 

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