Nitrile imines, cycloaddition with

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). ... 

Highly functionalized tetraaryl-4,5-dihydro-l,2,4-triazoles 118a-y have been prepared on a soluble polymer support (PEG4000) from the cycloaddition of diarylimines with a nitrile imine, prepared in situ from the arylhydra-zone 119. The triazole products are highly fluorescent and several have reasonable fluorescence quantum yields (Scheme 8 and Table 19) <2005S3535>. 

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>. 

Less frequently applied are [3 + 2] and [2 + 2] cycloadditions of oxygen-substituted allenes [102-104], Battioni et al. described only a limited number of [3 + 2] cycloadditions of phenyloxy- and methoxyallene with diphenyldiazomethane (157) and the nitrile imine derived from diphenylhydrazonoyl chloride (159) (Scheme 8.40) [102], Both 1,3-dipoles exclusively attack the terminal C=C bond, furnishing cycloadducts 158 and 160. Padwa et al. reported [3 + 2] cycloadditions of methoxyallene 145 with two nitrones which afforded isoxazolidines in low yield [103]. 

Dihydrodiazepines have been shown to undergo regioselective cycloaddition reactions with nitrile oxides or nitrile imines (88MI1 89JHC1619). 

Thus in the N-silyl substituted series, 17 and 18, which rearrange thermally to the corresponding diazo compounds, the stability increases through the series R=Me, Ph, i-Pr. As discussed below, these compound undergo the usual cycloaddition and electrocyclization reactions of nitrile imines and are not simply overstabilized curiosities. The usefulness in synthesis of those with P—C bonds is probably limited since these bonds are not easily broken, but products derived from those with C—Si and C—B bonds (e.g., 21 and 22) should be capable of further... 

Variously substituted nitrile imines are easily available and react readily with a wide range of double and triple bonds. Intermolecular cycloaddition is therefore an area of major interest, and a large proportion of the papers on the use of nitrile ylides in synthesis is concerned with the exploitation of this reaction. Space limitation means, regrettably, that work leading to results that were predictable on the basis of known chemistry (19) has generally not been included. 

Extensive studies on diastereoselectivity in the reactions of 1,3-dipoles such as nitrile oxides and nitrones have been carried out over the last 10 years. In contrast, very little work was done on the reactions of nitrile imines with chiral alkenes until the end of the 1990s and very few enantiomerically pure nitrile imines were generated. The greatest degree of selectivity so far has been achieved in cycloadditions to the Fischer chromium carbene complexes (201) to give, initially, the pyrazohne complexes 202 and 203 (111,112). These products proved to be rather unstable and were oxidized in situ with pyridine N-oxide to give predominantly the (4R,5S) product 204 in moderate yield (35-73%). 

Cycloadditions have been carried out to 37/-indoles (222, 223) (125,126), N-arylmaleimides (224) (127,128), l,2), -azaphospholes (225) (129), 5(47/)-oxazo-lones (226) (130), and 4,5-dihydrooxazoles (230) (131). The primary cycloadducts from the reaction of oxazolones (e.g., 226 with diaryl nitrile imines), derived from tetrazoles in refluxing anisole, do not survive. They appear to lose carbon dioxide and undergo a dimerization-fragmentation sequence to give the triazole 228 and the diarylethene 229 as the isolated products (130). In cases where the two aryl substituents on the oxazole are not the same, then, due to tautomerism, isomeric mixtures of products are obtained. 

Trifluoroacetylacetonitrile (396) can also react with nitrile imines 395 via two reaction paths depending on their structure. Those with an electron donating N substituent reacted via cycloaddition to the enolic double bond to give 397 while... 

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. 

---