Tosyl isocyanate 3+2 cycloaddition reactions

When acrylonitrile or ethyl acrylate was used as the dipolarophile, the azomethine adducts (134) and (135) were formed no thiocarbonyl ylide addition products were isolable in refluxing toluene or xylene, although the isoindoles (136a) and (136b) derived from them were isolated. In contrast to the reactions with fumaronitrile or AT-phenylmaleimide, the azomethine adducts (134) and (135) were still present at higher reaction temperatures — almost 50% in toluene and 4-5% in xylene. Under the same reaction conditions other electron-deficient dipolarophiles like dimethyl fumarate, norbornene, dimethyl maleate, phenyl isocyanate, phenyl isothiocyanate, benzoyl isothiocyanate, p-tosyl isocyanate and diphenylcyclopropenone failed to undergo cycloaddition to thienopyrrole (13), presumably due to steric interactions (77HC(30)317). 

Ketenes react with imines via [2+2]-cycloaddition to produce P-lactams.278 An example is the reaction of the acid chloride of phenylacetic acid with Proton Sponge to give ketene 340, which reacted with the tosyl imine shown and a quinuclidine catalyst to give a 65% yield of P-lactam 341, in 96% ee.229 A-Substituted isocyanates also undergo thermal [2+2]-cycloaddition reactions with alkenes, generating P-lactams.280... 

The reaction between tri-O-acetyl-D-glucal 7 and chlorosulfonyl isocyanate has been studied in the past, but neither formation of a cycloadduct nor of a rearranged product has been observed. Isocyanate acted only as acid catalyst causing decomposition of sugar material. On the other hand, [2+2]cycloaddition of active isocyanates to dihydro-2H-pyran and to its derivatives has been widely investigated, under a variety of conditions. The reaction of tosyl isocyanate with dihydro-2H-pyran 1 at low temperature (0 ) led to the formation of bicyclic p-lactam 2. Elevation of the cyclization temperature resulted in the rearrangement of the four-membered ring to the open-chain amide 3 (Scheme 4). 

The reversibility and thermodynamic control of product formation found for the high-pressure reaction between glycals and tosyl isocyanate indicated that the [2+2]cycloaddition of isocyanates to glycals could occur at atmospheric pressure under specific reaction conditions including an excess of isocyanate, as well as proper selection of solvent and substrates. Acyl isocyanates are generally less reactive in [2+2]cycloaddition reactions than sulfonyl isocyanates, except for trichloro- and trifluoroacetyl isocyanate 10,12 addition, acyl isocyanates are problematic because of the competitive formation of [4+2]cycloadducts, which are usually thermodynamically preferred over the [2+2]cycloadducts. 

High pressure also promotes the [2+2] cycloaddition reactions of enol ethers with isocyanates derived from amino acids The reaction of tri-O-acetyl-o-glucal with tosyl isocyanate proceeds similarly under high pressure, but at atmospheric pressure the cycloadducts revert to the starting materials... 

The reaction of 2-phenylimino-l,3-thiazine 119 with tosyl isocyanate proceeds via a [2+2] cycloaddition across the the C=N bond to give 2-(p-toluenesulfonyl)imino-l,... 

Likewise, imidoyl ketenimines 153 react as 1-aza-1,3-dienes in [4-1-2] cycloaddition reactions with phenyl isocyanate to give the cycloadducts 154 (62-67 % yields) or with tosyl isothiocyanate to give the cycloadducts 155 (62-69 % yields) . ... 

In 2014, it was shown that cross-conjugated 1-azatrienes ([3]-l-azadendralenes) 81 could also participate in the DTHDA cycloaddition (Scheme 2.13) [23]. The 1-azatrienes 81 prepared in situ from aldehydes 80 and amines underwent the initial HDA reaction with tosyl isocyanate to afford the mono-adduct 82 in high yields. The second DA reactions with TCNE and Ph-MI proceeded smoothly at rt or 113 C to produce bis-adducts 83 and 84, respectively, in good yields with high diastereo-ic-facial selectivity for both 83 and 84 and with endo selectivity for 84. 

A successful method for preparing 1,3-thiazetidines is the cycloaddition of carbodiimides with isocyanates. The cycloadduct 151 was derived by the interaction of carbodiimide 152 and tosyl isothiocyanate . Reaction of 152 with methyl or phenyl isothiocyanate preferentially leads to iminotriazine-thiones. Cycloaddition between aryl isothiocyanates and dicyclohexylcar-bodiimide produced 153. ... 

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