Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology , 4, Raja S. C. Mullick Road, Kolkata, West Bengal 700 032, India.
J Org Chem. 2018 Feb 16;83(4):2114-2124. doi: 10.1021/acs.joc.7b03054. Epub 2018 Feb 8.
Cu(II)-catalyzed reaction of α-keto thioesters with trimethylsilyl azide (TMSN) proceeds with the transformation of the thioester group into urea through C-C and C-S bond cleavages, constituting a practical and straightforward synthesis of N-acylureas. When diphenyl phosphoryl azide (DPPA) is used instead as the azide source in an aqueous environment, primary amides are formed via substitution of the thioester group. The reactions are proposed to proceed through Curtius rearrangement of the initially formed α-keto acyl azide to generate an acyl isocyanate intermediate, which reacts further with an additional amount of azide or water and rearranges to afford the corresponding products. To demonstrate the potentiality of the method, one-step syntheses of pivaloylurea and isovaleroylurea, displaying anticonvulsant activities, have been carried out.
Cu(II)催化的α-酮硫代酯与三甲基硅基叠氮化物（TMSN）的反应通过 C-C 和 C-S 键的断裂，将硫酯基团转化为尿素，构成了 N-酰基脲的实用且直接的合成方法。当二苯基磷酰叠氮化物（DPPA）在水相环境中用作叠氮源时，通过硫酯基团的取代反应形成伯酰胺。反应被认为是通过最初形成的α-酮酰基叠氮化物的Curtius 重排进行的，生成酰基异氰酸酯中间体，该中间体与额外量的叠氮化物或水进一步反应并重排得到相应的产物。为了证明该方法的潜力，已经进行了具有抗惊厥活性的特戊酰基脲和异戊酰基脲的一步合成。
