Nitrile imines, 1,3-dipolar

The characteristics of the 1,3-dipolar cycloaddition mechanism of azides and other 1,3-dipoles (such as diazoalkanes, azo-methine imines, nitrones, nitrile imines, nitrile oxides) have been described in detail by Huisgen.191 19 According to the author, the addition of a 1,3-dipole (a b c) to a dipolarophile (d e) occurs by a concerted mechanism in which the two new a bonds are formed simultaneously although not necessarily at equal rates (32). As a consequence, a stereoselective cis addition is observed. Thus, the addition of p-methoxyphenyl azide to dimethyl fiynarate (33) yields l-(p-methoxyphenyl)-4,5-froiw-dicarbomethoxy-AMriazoline (34),194 and 4-nitrophenyl azide gives exclusively the respective cis-addition products 35 and 36 on addition to irons- and cis-propenyl propyl ether.196... 

The concept of intramolecular 1,3-dipolar cycloaddition reaction has been extended to include azides, azomethine imines, nitrile oxides, nitrile imines and azomethine ylides. Such reactions are summarized in Table 1. 

Bent 1,3-dipolar systems such as ozone, nitrile imines, nitrile oxides, nitrous oxide, and bent allenoid azides are devoid of stereochemical handles at the termini nevertheless they have well-defined molecular faces, and if needed, the HED system can be applied to them as well. 

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

Another 1,7-dipolar cyclization leading to 1,2-benzodiazepines, but with the difference that a C-C bond is formed, is the ring closure of the nitrile imines 15 to give 17 by a [1,5]-sigmatropic shift of hydrogen in the intermediates 16. The nitrile imines are generated from the (2-vinylphenyl)hydrazonoyl chlorides 14."8 120... 

Nitro compounds are versatile precursors for diverse functionalities. Their conversion into carbonyl compounds by the Nef reaction and into amines by reduction are the most widely used processes in organic synthesis using nitro compounds. In addition, dehydration of primary nitro compounds leads to nitrile oxides, a class of reactive 1,3-dipolar reagents. Nitro compounds are also good precursors for various nitrogen derivatives such as nitriles, oximes, hydroxylamines, and imines. These transformations of nitro compounds are well established and are used routinely in organic synthesis. 

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 ... 

---