Different modes of acid-catalyzed cyclization of 4-(γ-oxoalkyl)semicarbazide hydrazones: 7-membered versus 14-membered cyclic semicarbazones formation

A General Stereoselective Approach to 1,2,4-Triazepane-3-thiones/ones via Reduction or Reductive Alkylation of 2,4,5,6-Tetrahydro-3H-1,2,4-triazepine-3-thiones/ones

“…Readily available 2,4,5,6-tetrahydro-3H-1,2,4-triazepine-3-thiones/ones 3a-k [18,19,42] served as starting material for the present investigation. Among a large variety of reductants which could be used for C=N double bond reduction [45][46][47][48][49][50] we chose sodium cyanoborohydride [51][52][53][54][55].…”

“…The 1 H NMR spectra of 4a-k in DMSO-d6 show a long-range coupling between the (thio)amide N(2)H and N(4)H protons ( 4 J = 2.0-2.5 Hz) that indicates their one-plane W-shaped arrangement. Similar long-range couplings are characteristic of N-unsubstituted (thio)ureide-containing heterocycles, e.g., 2,3,4,5-tetrahydroand 2,3-dihydro-1H-1,3-diazepin-2-ones [57][58][59][60][61], hexahydro-and 1,2,3,4-tetrahydropyrimidine-2thiones/ones [57][58][59][60][61][62][63][64][65][66][67][68], 2,4,5,6-tetrahydro-3H-1,2,4-triazepine-3-thiones/ones [18,19,42]. Two alternative procedures were developed for preparation of 1-alkyl-substituted 1,2,4-triazepane-3-thiones/ones.…”

“…The reported syntheses of 1,2,4-triazepin-3-ones/thiones include the reaction of β-isocyanato and β-isothiocyanato ketones with hydrazines [16][17][18][19][20][21][22][23][24], condensation of semicarbazides and thiosemicarbazides with various 1,3-dicarbonyl compounds or their derivatives [10,[25][26][27][28][29][30][31][32][33], reaction of arylidene ketones with N2H4•2HNCS [34], addition of semicarbazides and thiosemicarbazides to α,β-unsaturated carbonyl compounds or their synthetic equivalents [35][36][37][38][39], reaction of γ-hydrazinosubstituted amines with phosgene equivalents [8,[13][14][15]40], and intramolecular cyclization of 4-(γ-oxoalkyl)semicarbazides and 4-(γ-oxoalkyl)thiosemicarbazides or their derivatives [17,22,41,42]. Generally, these methods give access to 1,2,4-triazepin-2-ones/thiones with one or two double bonds in the 7-membered ring.…”

“…We rationalized that these compounds could be prepared by reductive transformations of 2,4,5,6-tetrahydro-3H-1,2,4-triazepin-2-ones/thiones. Previously, we developed effective syntheses of the latter based on acid-catalyzed cyclization of 4-(3-aryl-3-oxopropyl)(thio)semicarbazides and their hydrazones [18,42] or base-promoted ring expansion of 3-amino-4-hydroxyhexahydropyrimidine-2-thiones [19].…”

Asymmetric Organocatalysis Revisited: Taming Hydrindanes with Jørgensen–Hayashi Catalyst

“…Such deacetylation under basic conditions has been reported for several acetylacetone derivatives. [40][41][42][43] Due to the failure of the base-mediated cyclizations, we focused on the corresponding acid-catalyzed aldol condensation. Indeed, treatment of aldehyde 10a with 0.1 equivalent of TsOH in toluene under reflux for 3 hours gave 9a in 5% yield ( Table 3, entry 3).…”