Vinyl isocyanates, Curtius rearrangement

Heteroaromatic vinyl isocyanates have been used as a source of bicyclic pyridones. In the preparation of the l-methylpyrazolo[4,3-c]pyridone 153 the isocyanate 152b, obtained by Curtius rearrangement of the corresponding acid azide 152a, was heated at 220°C in diphenyl ether to furnish the product in good yield.143,144 Several 2-alkyl derivatives were also prepared.144... 

Alkyl-, vinyl-, and aryl-substituted acyl azides undergo thermal 1,2-carbon-to-nitrogen migration with extrusion of dinitrogen — the Curtius rearrangement — producing isocyantes. Reaction of the isocyanate products with nucleophiles, often in situ, provides carbamates, ureas, and other A-acyl derivatives. Alternatively, hydrolysis of the isocyanates leads to primary amines. 

Ene-carbamates 499 can be prepared via a Curtius rearrangement of a hydrolyzed MBH adduct 498 followed by the reaction of intermediate vinyl isocyanates with an alcohol (methanol or f-butanol). In addition, different acyloin (a-hydroxyketones) 500 have been obtained in good overall yields based on a Curtius rearrangement in the presence of water. These methodologies have been demonstrated in the synthesis of some bioactive compounds (501and 502) (Scheme 3.219). 

Activation of the carboxylic acid as the acyl chloride permits direct reaction with azide anion to form the acyl azide substrates for Curtius rearrangement. Sodium azide is commonly used, and the reaction has been used on the process chemistry scale for the synthesis of benzyl-A-vinyl carbamate. Acryloyl chloride was combined with sodium azide in a biphasic system with phase-transfer catalysis (PTC), providing acyl azide 25. Upon heating, Curtius rearrangement provided vinyl isocyanate, which was distilled directly into benzyl alcohol containing phenothiazine (27) to inhibit polymerization of 26 and triethylamine to catalyze addition of the alcohol to the isocyanate. The vinyl carbamate product 28 was isolated by crystallization. As the autiior clearly pointed out, preparation and reaction of acyl azides, particularly on large scales, require appropriate safety precautions. 

These azides undergo Curtius rearrangement to vinyl isocyanates, which are prone to polymerization. Where polymerization does not interfere, hydrolysis of the vinyl isocyanate provides aldehydes or ketones via the enamine. Bomylene carbonyl azide (47) yielded epicamphor (48) via the Curtius rearrangement-hydrolysis sequence. ... 

The Curtius rearrangement of acyl azides preserves double bond geometry. The vinyl isocyanate can be trapped by nucleophiles rather than hydrolyzed. Examples capitalizing on the Shioiri and Weinstock procedures are diseussed in the Variations and Improvements Section (see 60, 62, and 90). 

Another vinyl isocyanate was involved in the Curtius-mediated synthesis of fiiranyl heterocycle 63. The acyl azide precursor was obtained from (Z)-alkenyl carboxylic acid 62 using the Weinstock conditions. Upon Curtius rearrangement, the pendant fliran cyclized onto the resulting (Z)-vinyl isocyanate. 

An improved method that can be easily scaled-up has been developed for the preparation of benzyl-N-vinyl carbamate 810 (Z-vinylamine), a valuable synthetic intermediate in the synthesis of p-lactam antibiotics [589]. In this method, vinyl isocyanate 809, formed by the Curtius rearrangement of acryloyl azide 808, is codistilled with a solvent such as toluene into benzyl alcohol containing a catalyst and an inhibitor. The product thus obtained can be purified by crystallization, thereby avoiding purification by high-vacuum distillation or chromatography. Potential safety issues associated with the process are important [590, 591]. 

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