Synthetic route towards 1,2,3,4-tetrahydroquinoxaline/piperidine combined tricyclic ring system

The synthetic route toward novel tricyclic, nitrogen-containing system is disclosed. Three novel compounds possessing structural features of 1,2,3,4-tetrahydroquinoxaline and decahydropyrido[3,4-b]pyrazine are synthesized starting from readily available precursors in six or seven steps, of which the last three or four steps respectfully are diastereoselective. Key reaction steps include N-acylation, Hofmann rearrangement and ring-closing Buchwald-Hartwig reaction. Compounds trans-8, cis-12 and trans-12 are synthesized in order to prove that this novel, tricyclic system can be functionalized with various groups. Synthetic significance of this heterocyclic system lies in the possibility for the orthogonal functionalization of three different amino groups, allowing fine structural tuning.

Synthesis of unsymmetrical urea from aryl- or pyridyl carboxamides and aminopyridines using PhI(OAc)2 via in situ formation of aryl- or pyridyl isocyanates

A tandem synthesis of unsymmetrical urea (N-aryl-N'-pyridylurea and N,N'-bipyridylurea) from aryl- or pyridyl carboxamides and aminopyridines via Hofmann rearrangement has been developed. In particular, benzamides, picolinamide, nicotinamide, and isonicotinamide generate...

A Straightforward Synthesis of N-Substituted Ureas from Primary Amides

A direct and convenient method for the preparation of N-substituted ureas is achieved by treating primary amides with phenyliodine diacetate (PIDA) in the presence of an ammonia source (NH3 or ammonium carbamate) in MeOH. The use of 2,2,2-trifluoroethanol (TFE) as the solvent increases the electrophilicity of the hypervalent iodine species and allows the synthesis of electron-poor carboxamides. This transformation involves a nucleophilic addition of ammonia on the isocyanate intermediate generated in situ by a Hofmann rearrangement of the starting amide.

Recent Advances in the Hofmann Rearrangement and Its Application to Natural Product Synthesis

: C-N bond formation reactions are the most important transformations in (bio)organic chemistry because of the widespread occurrence of amines in pharmaceuticals, natural products, and biologically active compounds. The Hofmann rearrangement is a well-known method used for the preparation of primary amines from amides. But, the traditional version of the Hofmann rearrangement often gave relatively poor yields due to over-oxidation or due to the poor solubility of some amides in aqueous base, and created an enormous amount of waste products. Developments over the last two decades, in particular, have focused on refining both of these factors affecting the reaction. This review covers both the description of recent advances (2000-2019) in the Hofmann rearrangements and its applications in the synthesis of heterocycles, natural products and complex molecules of biological interest. It is revealed that organo-catalytic systems especially hypervalent iodine-based catalysts have been developed for the green and environmentally friendly conversion of carboxamides to primary amines and carbamates.

Hypervalent iodine reagent-mediated reactions involving rearrangement processes

We summarize the developments of hypervalent iodine reagents-mediated reactions involving [1,2]-migration, Hofmann rearrangement, Beckmann rearrangement, ring contraction/expansion, [3,3]-sigmatropic/iodonium-Claisen rearrangement and some miscellaneous rearrangements.