Alexey V. Lesiv

Chemistry of N,N-Bis(silyloxy)enamines, Part 5†

Aliphatic nitro compounds can be considered as good precursors of a wide variety of α-azolyl-substituted oximes. The double silylation of convenient aliphatic nitro compounds and the subsequent N,C-coupling of the resulting N,N-bis(silyloxy)enamines 3 with N-silylated azoles 4 lead to the formation of the silylated α-azolyl-substituted oximes 6, which can be smoothly desilylated to give the target α-azolyl-substituted oximes 5. The mechanism of the key step of this process – N,C-coupling – includes the generation of corresponding conjugated nitrosoalkenes 7 (Schemes 4 and 5). The contribution of the chain mechanism in the overall process is considered as well. The studies of the scope and limitations of this reaction, as well as the optimization of its conditions were accomplished. The configuration of the CN bond in oximes was established by NMR.

Unusual Intramolecular Cyclization of Tris(β-oximinoalkyl)amines. The First Synthesis of 1,4,6,10-Tetraazaadamantanes

An unusual intramolecular cyclization of tris(beta-oximinoalkyl)amines 1 into 4,6,10-trihydroxy-1,4,6,10-tetraazaadamantanes 2 was discovered. Compounds 2 are related to a previously unknown type of heteroadamantanes that contain the cage isomeric to urotropin. A simple three-step synthesis of tetraazaadamantanes 2 and their N-substituted derivatives 3 and 4 from ammonia and aliphatic nitro compounds via the intermediacy of available tris-oximes 1 was developed.

Syntheses based on α-azidooximes: I. Reduction of α-azidooximes

Convenient procedures were developed for selective and exhaustive reduction of α-azido-oximes that were easily prepared from aliphatic nitro compounds. Nitroalkanes were shown to be convenient precursors of β-functionalized amines (1,2-diamines, iminophosphonates, β azidohydroxyl-amines, α-aminooximes).

Syntheses based on α-azidooximes: II. Preparation of 6,7-dihydrotriazolopyrazinones from aliphatic nitro compounds

Abstractα-Azidooximes readily obtained from aliphatic nitro compounds were cleanly converted into previously unknown 6,7-dihydro[1,2,3]triazolo[1,5-a]pyrazin-4(5H)-ones via [3+2]-cycloaddition to dimethyl acetylenedicarboxylate and reduction of the oximino group in forming intermediates.

Stereoselective Synthesis ofUnnatural β-Amino Acids from Nitroethane via 5,6-Dihydro-4H-1,2-oxazin-3-ylacetates

The reduction of easily available methyl 5,6-dihydro-4H-1,2-oxazin-3-ylacetates provides an efficient route to different diastereomerically pure unnatural β-amino acids. A two-step protocol including reduction of the C=N bond of the initial oxazine with sodium cyanoborohydride during the first step and hydrogenation of the N-O bond during the second step produced the target β-amino acid esters with higher stereoselectivity than obtained with conventional catalytic hydrogenation.

Synthesis of Substituted 5-(3-Hydroxypropyl)pyrrolidin-2-onesand Pyrrolizidinones from Nitroethane via C3 Functionalized 5,6-Dihydro-4H-1,2-oxazines: A Novel Approach to SomeAnalogues of the Antidepressant Rolipram

Easily accessible [(5,6-dihydro-4H-1,2-oxazin-3-yl)methyl]malonates 1 were converted into substituted 5-(3-hydroxypropyl)pyrrolidin-2-ones 2 and pyrrolizidinones 3, which are versatile products and intermediates for organic and bioorganic chemistry. The synthetic sequence suggested includes stereoselective two-step reduction of an oximino fragment, followed by intramolecular cyclization involving one of the CO 2 Me groups and decarboxylation in the last stage. The efficiency of this strategy was demonstrated by the stereoselective synthesis of pyrrolizidinone rac-4, a highly efficient analogue of antidepressant Rolipram, from nitroethane.