Imino ketenimines

Monocyclic imino-ketenimines, in which the reactive functionalities are linked by an allylic or vinylic tether connecting the imino and ketenimino nitrogen atoms, undergo a formal intramolecular [2+2] cycloaddition to yield fused tricyclic 2-iminoazetidines, namely, azeto[l,2-a][l,3]thiazolo[4,5-rf] [pyrimidines 10 <02EJO4222>, and azeto[l,2-... 

The chiral imino ketenimine 47 is similarly converted to a single intramolecular cycloadduct 48 with a yn-relative configuration between two adjacent stereo centers... 

Azeto[l,2]imidazoles 56 are also obtained in low yields by a formal intramolecular [2+2] cycloaddition reaction of the imino ketenimines 55/ ... 

Ketenimines are usually prepared from carboxyHc acid derivatives such as amides and imino chlorides via elimination and from nitriles via alkylation with alkyl haHdes under strong basic conditions (21,64). 

Flash vacuum pyrolysis (FVP) of the 3-(iV-(pyrimidin-2-yl)imino-l-morpholino)propanoate 179 led to pyrimido-pytimidines 182 and 184, as a result of competition between thermal loss of ethanol or morpholine. The ketenimine 181, being unable to undergo cyclization, underwent [l,3]-ethoxy migration to form 183, leading to 184 (Scheme 28). The ratio of the products was studied on variation of the temperature (400, 530, and 600 °C) and the nature of the amino substiuent (NR1R2 = morpholino, pyrrolidino, N(Me)Ph ) <2004AJC577>. 

Ketenimines have been observed to participate in imino-ene reactions.32 Conversion of 34 into 35 could be controlled by ortho-substitution on the aryl rings (Scheme 4). For example, if Ar = 2,6-(CH3)2-C6H3, only 35 was obtained in 70% yield and none of the [2 + 2]-cycloadduct 36 was observed. 

The addition of cis-azobenzenes to ketenimines gives 3-imino-l,2-diazetidines which cleave to give carbodiimides and imines upon thermolysis (Scheme 4) (67JHC155, 72JHC555, 74JHC409). l,2-Diphenyl-l,2-diazetidin-3-one has similarly been reported to fragment to isocyanate and imine (56AG71). 

The intermediacy of a 4-imino- 1,2-oxathietane 2-oxide from the addition of sulfur dioxide to ketenimines was inferred from the trapping with methanol. The final isolated product in absence of methanol, l,2-thiazetidin-3-one 1-oxide, was established by X-ray (Scheme 42) (81CC350). 

Both carbodiimides and ketenimines are reported to add to N-sulfinylsulf amides to give 3-imino- and 3-alkylidene-l,2,4-thiadiazetidine 1-oxides, (Scheme 135) (73BCJ2156, 75BCJ3259). The adducts were identified from both IR and NMR spectra and from hydrolysis products. 

Diazetidinones are prepared by the thermal [2 + 2] cycloaddition of ketene with diazo compounds (Scheme 3) (83HC(42)443). Use of ketenimines instead of ketene furnished imino derivatives (67JHC155). 

Upon prolonged irradiation in the presence of an excess ketone, the monoadducts are converted into 1,5- and l,6-dioxaspiro[3.3]heptanes (e.g., 80a,b) [53]. The regioisomeric 2- and 3-imino-oxetanes could be prepared by photolysis of ketenimines in the presence of aliphatic or aromatic ketones [72]. 

Annelatlon reactions. The ketenimine 1 acts chemically as a vinyl phosphonate activated by the cumulated imino group and is useful as an annelation reagent for the synthesis of heterocyclic compounds. As such it condenses with the sodium salt of salicylaldehyde (2) to afford the benzopyrane in 3 in 52% yield. Similarly, the pyrrolizine 5 is available from the sodium salt of 2-formylpyrrole in 51% yield. ... 

Pd(PPh3>4]- or (PhO)3P/[Ni(COD)2]-catalyzed [3 + 2] cycloadditions of methylenecyclopropanes with ketenimines (66) lead selectively to pyrroles (67 equation 26), (68) and (69 (equation 27), or a-methylene-A -pynolines (70 equation 28) depending on the sutetituents of the imino group and the methylenecyclopropanes. Diphenylketene-N-methylimine reacts with (26) to give l-methylimino-3-methyl-5,5-diphenylcyclopent-2-ene in 38% yield. ... 

A number of 2-iminothietanes have been prepared from ketenimines and thio-benzophenone ° or thioxanthone. Addition of carbon oxysulfide or carbon disulfide to the phosphonium ylide of a ketenimine 312 gives an imino- 3-dithiolactone as previously noted.Arylsulfonylisothiocyanates undergo cycloaddition at 50°C to vinyl ethers to give 2-iminosulfonylthietanes in 50-76% yields.A ( 2g -I- 2 ) process involving zwitterions was suggested on the basis of the observed stereochemistry. 

Bis(imino) thietanes, 343, 344, are prepared by reaction of isonitriles with iminothiiranes or of ketenimines with p-tolylsulfonyl isothiocyanate. Reaction of phosphonium ketimine ylides, for example, 312, and related compounds with isothiocyanates also gives bis(imino) thietanes, for example, 345. " Treatment of arylsulfonyl isothiocyanates with trimethylacetoisonitrile yields tris(imino)-thietanes, for example, 341. ... 

Ai7lmethylene-3-phenyl-2-isoxazolin-5-ones 36 I eact with A-phenacylpyridinium bromide in the presence of triethylamine to give stable betaines 37 <97LA441>. Flash-vacuum pyrolysis of the isoxazolinone 38 results in the ketenimine 39, together with the bis(imino)propadiene 40 <96MI1318>. 

The synthesis of imino-penam and -cephem derivatives has also been investigated using the [2 + 2] cycloaddition of ketenimines to Schiff bases as the key-step [24]. N-(aryl) and N-(alkyl)ketenimines are not electrophilic enough to react with Schiff bases. On the other hand, iV-(tosyl)ketenimines 25 were susceptible to nucleophilic attack by imines (Scheme 9). They were readily generated in situ from the corresponding sulphimides 23. The a-bromo-iminium bromide intermediates 24 reacted with Schiff bases and triethylamine to give JV-(tosyl)azetidin-2-imines 26. 

Ketenimine 446 lagem Ylide 34 imter Bildung der stabilen N-Aiyl-a-imino-alkyliden-triphenylphosphorane 447 an... 

For example, treatment of imino chloride 144 derived from 7p-(2-phenyl-2-bromo) acetamido-3-methyl 3-cephem benzhydryl ester (143) and phosphorus pentachloride, with an excess of methanolic lithium methoxide in THF at -78°C for 20 min, followed by quenching with acetic acid, afforded 7 -phenylketenimino-7a-methoxy- -lactam (146) in 60% yield. This material was reasonably stable to silica gel chromatography and, when treated with trifluoroacetic acid followed by aqueous quenching, quantitatively afforded 7p-phenylacetamido-7a-methoxy-3-methyl-3-cephem-4-carboxylic acid. Similar treatment of imino chlorides (144) or ketenimines (146) with lithium methoxide at -20 C provided iminoethers (147) in good yield. In the case of the imino chloride formed from 7p-dichloroacetamido-7-deacetoxycephalosporanic acid methyl ester, the corresponding iminoether (147) was obtained in 80% yield with lithium methoxide, even at — 78°C. The same imino chloride reacted... 

Imino-l,2-dioxetans, which have been synthesized independently by several groups of workers, are available by reaction of ketenimines and singlet oxygen in one step. The dioxetans may be decomposed by photochemical means to give the expected ketones and isocyanates. 

The [2+2] cycloaddition reaction between ketenimines and aldehydes is also catalyzed by Y+ and Eu+ shift reagents Heating of the respective iminooxetanes in the presence of the same catalysts causes formation of the isomeric -lactams Also, duroquinone reacts photochemically with Ph2C=C=NPh to give the isomeric imino... 

Likewise, the imino(acylimino)ketenimines 51, generated in situ, undergo an intramolecular cycloaddition reaction to give 52. ... 

Across N=N bonds Another pronounced [2+2] cycloaddition reaction of ketenimines is their addition to the N=N bond in cis-azomethines to give the imino-l,2-diazetidines 62 and 63. This reaction is conducted with UV irradiation to convert the unreactive trans-azobenzenes into the reactive cis-cis compounds. Asymmetrically substituted azobenzenes afford mixtures of the two regio isomers. Electron donating substituents on the azobenzenes increase the rate of addition. Some of the [2+2] cycloadducts obtained in the reaction of ketenimines with azo compounds are listed in Table 4.22. 

Table 4.22 Imino-1,2-diazetidines by [2- -2] cycloaddition of cis-azobenzenes to ketenimines...

The [2+2] cycloaddition reaction of isothiocyanates with ketenimines proceeds at room temperature across the C=S bond of the isothiocyanates and the C=C bond of the ketenimines to give 2,4-bis(imino)thietanes. However, only reactive isothiocyanates, such as arenesulfonyl isothiocyanates (48-54 % yield) or phenylcarbonyl isothiocyanate (44 % yield), undergo this reaction... 

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