Vinyl isocyanates, reaction with enamines

Vinylic isocyanates react with enamines such as 1-pyrrolidino-l-cyclohexene under mild conditions to form a new pyridinone ring and simultaneous loss of pyrrolidine [3S40]. Reaction of an ynaminone with phenyl isocyanate in refluxing THF gives good yields of 3-acyl-4-dimethylamino-2-quinolinone [2056]. A perchloroynamine behaves similarly [2838]. 

Vinyl isocyanates also undergo a [2+4] cycloaddition reaction with enamines 500 to give the [4+2] cycloadduct 501 in 81 % yield... 

Vinyl ethers undergo many cycloaddition reactions similar to those which take place with enamines. In general, however, these cycloaddition reactions with vinyl ethers take place less readily than those with enamines. These reactions include cycloaddition of vinyl ethers with ketene (200-205), phenyl isocyanate (206), sulfene (207,208), methyl acrylate (209), diethyl acetylenedicarboxylate (210), and diphenylnitrilimine (183). 

Other notable methods involve Hetero Diels-Alder reactions [20,21], and the reaction of vinyl isocyanates with enamines [22,23]. 

The reaction of vinyl isocyanates of type 123 with enamines gives intermediates containing the enaminoamide moiety, which subsequently undergoes an intramolecular cyclization and affords phenanthridine derivatives (84JOC4569). Numerous polyheterocycles were synthesized similarly (89JOC224). 

An interesting variant of the annulation of enamine substrates with acrylic acid derivatives was the thermal reaction of enamines with vinyl isocyanates (eq. 17).31 Treatment of 68 with DPPA produced the intermediate vinyl isocyanate, which underwent cycloaddition with the enamine followed by elimination of the pyrrolidine to give pyridone 70. Pyridone 70 was efficiently converted to the corresponding highly substituted pyridine. 

The more common triazine to pyridine ring transformation is illustrated by the formation of pyridines by reaction of 2,5,6-triethoxycarbonyl-1,2, -triazine with both alkynes and enamines.30,31 The addition of vinyl isocyanate to 1-diethylamino-propyne gives mainly the pyridone (1 ) as a result of initial (2+2) cycloaddition followed by rearrangement the thiopyridone (15) is however formed from the corresponding reaction with vinyl isothiocyanate as a consequence of a (A+2)cycloaddition reaction.32... 

The [2+2] cycloaddition reaction of isocyanates proceeds better with olefins having electron donating groups attached to the double bond system. Examples include vinyl ethers, enamines, ketene acetals, tetraalkoxy- or tetraalkylaminooleflns. The more reactive sulfonyl and carbonyl isocyanates undergo cycloaddition reactions with vinyl ethers especially well. For example, the reaction of vinyl ethers with p-toluenesulfonyl isocyanate affords the [2+2] cycloadducts in a stereospecific reaction... 

The more common triazine to pyridine ring transformation is illustrated by the formation of pyridines by reaction of 2,5,6-triethoxycarbonyl-1, 2,4--triazine with both alkynes and enamines.30,31 addition of vinyl isocyanate to 1-diethylaraino-... 

Aromatic and aliphatic acyl isocyanates participate in a similar range of [4 + 2] cycloadditions although [2 + 2] and simple addition reactions often are observed. The acyl isocyanate substituents may determine or alter the observed course of the reaction, and the substituent effects have been detailed in extensive reviews.7,71 Observed [4 + 2] cycloadditions of acyl isocyanates with selected olefins, p-quinones, allenes, the carbon-carbon double bond of ketenes, electron-rich acetylenes, imines, dianils, ethy-lenediimines, enamines, enol ethers, ketene acetals, carbodiimides, azirines, and vinyl sulfides have been described.7 0 The reaction of aromatic acyl isocyanates with carbodiimides is not a simple, direct [4 + 2] cycloaddition but proceeds by a kinetic [2 + 2] cycloaddition followed by a subsequent rearrangement to provide the observed [4 + 2] cycloadduct [Eq. (40)].97... 

The reactivity of isocyanates in [2+2] cycloaddition reactions is as follows alkyl < aryl < nitroaryl << arenesulfonyl < halosulfonyl. Also, the reactivity of the substrate is determined by the substituents. For example, vinyl ethers and enamines are more reactive than olefins. Often the formation of the [2+2] cycloadducts involves polar linear intermediates, which can be intercepted by the isocyanate or the substrate to form six-membered ring [2+2+2] cycloadducts (see Section 3.3.1.4). Also, diynes react with isocyanates to give six-membered ring [2+2+2] cycloadducts. In the latter reactions catalysts play an important role. From Q, ty-diynes macrocyclic adducts are obtained. 

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