The Electrolytic Reduction of Bicyclic α-Aminoketones. A New Method for the Synthesis of Medium Rings¹ Containing Nitrogen^2,3

Peripheral synthesis of secondary medium-ring nitrogen heterocycles

“…At the time this project was initiated the preparation of secondary medium-ring azacycles was limited to two general methods: the ring expansion of cycloalkanones,10 and the electrolysis of ß-keto-1-azabicycloalkanes. 11 Although both of these syntheses are somewhat limited in scope by the availability of starting materials or the reaction conditions, a potentially general route has been described12 more re-cently which nicely complements those to be discussed in this paper.…”

“…Because of difficulties with transannular ringclosure during the hydrolytic removal of the carbamate group from an unsaturated medium-ring compound (vide infra), a method based on the known25 reaction of amides with lithium reagents was utilized. The desired S-ethylideneazacyclononane (11) was by far the major portion (93%) of the product of 5 and methyllithium, presumably26 because the secondary amine was tied up as a lithium salt of the carbinolamine intermediate until work-up and hence resistant to cyclization. The structure of 11 was proven by its spectral properties, the analysis of its styphnate, and its conversion to" the known6 N-methyl derivative 4 50%, which is highly competitive with methods12 leading to secondary medium-ring azacycles without the potentially useful transannular unsaturation.…”

Synthesis of 4-.beta.-D-ribofuranosyl-as-triazin-3(4H)-one 1-oxide a potential uridine antagonist

“…2.5-Dihydro-4-(2,3,5-tri-0-benzoyl-/3-D-ribofuranosyl)-os-triazin-3(4íf)-one (11).-Into a suspension of 6 (0.800 g, 1.435 mmol) and 5% Pd-on-charcoal catalyst (0.080 g) in CHCL (200 ml) was bubbled H2 for 90 min. The catalyst was then removed by filtration, and the clear solution was concentrated to dryness.…”

“…The first use of both proton and carbon-13 nmr to establish the glycosylation site has been reported by our laboratories in the case of l-/3-D-ribofuranosyl-l,2,4triazoles. 11 The assignment was based on the use of the previously reported a and ß substitution shifts (11) G. P. Kreishman, J. T. Witkowski, R. K. Robins, and . P. Schweizer, J. Amer.…”

“…The ease of reduction of the triazine ring of the nucleosides 6 and 8 to yield 2,5-dihydro-4-(2,3,5-tri-0benzoyl-/3-D-ribofuranosyl)-as-triazin-3(4//)-onc (11) and the analogous deblocked nucleoside 12 is of interest, since the reduction of the structurally related 6-azauridine is much more difficult.17•18 Attempts to prepare 3-hydroxy-as-triazine (13)10 by hydrogenation of 3-benzyloxy-as-triazine (14) furnished only the reduced product 2,5-dihydro-as-triazin-3(4A)one (15), the parent heterocycle of nucleosides 11 and 12 (Scheme II).…”