Hexahydro‐2‐oxo‐1,4‐diazocin‐6‐carboxylic acid constitutes a conformationally rigid, crown‐shaped scaffold. An orthogonally protected (Boc at N‐4 and methyl ester at 6‐CO2H) representative was prepared by ring expansion of a 3‐pyrrolidone‐derived 1,4‐diketone with MeNH2. After deprotection, this building block was further diversified by reductive aminations and amidations and by sulfonamide and urea formation. Furthermore, the 6‐CO2H function was transformed into a 6‐NHCbz group in one step by carboxamide degradation in the presence of BnOH. An example of a cyclic tripeptoidic structure was synthesized by amidation with N‐Boc‐β‐alanine and glycine methyl ester. Structural features of the eight‐membered heterocycle were established by single‐crystal X‐ray structure analysis of a 4‐bromoaniline derivative.

The reaction of Mo(II)acetate, concentrated triflic acid and the alkaline metal triflates A(CF(3)SO(3)) (A = Na, Rb, Cs) in sealed glass ampoules at 110 °C yielded red single crystals of A[Mo(2)(CF(3)SO(3))(5)]·2CF(3)SO(3)H (A = Na: triclinic, P-1, Z = 4, a = 13.714(1) Å, b = 14.339(1) Å, c = 21.340(2) Å, α = 81.78(1)°, β = 75.21(1)°, γ = 62.65(1)°; A = Rb/Cs: monoclinic, P2(1)/m, Z = 2, a = 11.561(1)/11.584(1) Å, b = 14.817(1)/14.9472(8) Å, c = 11.6208(1)/11.744(1) Å, β = 112.38(1)/113.48(1)°). The crystal structures contain dumbbell shaped [Mo(2)] moieties surrounded by three chelating and four monodentate triflate anions leading to an opening of the typical paddlewheel fragment at one of its edges. The monodentate triflate anions are connected to further [Mo(2)] dumbbells leading to infinite anionic chains according to (∞)(1)[Mo(2)(CF(3)SO(3))(3/1)(CF(3)SO(3))(4/2)](-). The charge balance is achieved by the alkaline metal ions that are additionally coordinated by triflic acid molecules. Theoretical investigations were preformed on the open paddlewheel fragment and are in good agreement with the experimental findings. According to DTA/TG measurements and the XRD investigations the decomposition of the compounds occurs in multiple steps and leads to MoO(2) and A(2)MoO(4).

Regioisomeric [c]annulated pyridazines were prepared from arylhydrazines and carbocyclic or heterocyclic β‐oxo esters with an α‐phenacetyl moiety. With AcOH/EtOH, the hydrazones were preferentially formed at the endocyclic ketone, which are further cyclized with trifluoroacetic acid (TFA)/CH2Cl2 to give 2,4a‐dihydropyridazines. Use of TFA/CH2Cl2 led hydrazones at the exocyclic benzoyl group, which reacted further to give 1,4‐dihydro‐4aH‐pyridazines. In this investigation, examples of the rare or unknown heterocyclic systems furo[3,4‐c]‐, thiopyrano[4,3‐c]‐ and pyrido[4,3‐c]pyridazine were prepared.

A ring enlargement reaction with methylamine gave new pyrido[2,3‐c]‐, pyrido[3,4‐c]‐ and pyrido[3,2‐c]azocanone derivatives from cyclic β‐oxo esters with a cyclopentapyridine skeleton and a 1,4‐diketone moiety. The starting materials for this ring transformation were either prepared from halogenopyridine carboxylates by Heck reaction and subsequent hydrogenation, or (halogenomethyl)pyridine carboxylates were submitted to SN reaction with diethyl malonate. Both routes were completed by Dieckmann condensation to build the cyclic β‐oxo ester structure and alkylation with phenacylbromide to install the 1,4‐diketone motif.

Three regioisomeric thieno[c]azocine derivatives were prepared in six steps from bromothiophene carboxylic acids. The reaction sequence started with an esterification with isopropyl alcohol. The resulting esters were submitted to a Heck reaction with tert-butyl acrylate followed by catalytic hydrogenation. Subsequent Dieckmann condensation gave cyclopentathiophenes with a cyclic β-oxo ester motif, which were α-alkylated with phenacyl bromide to furnish 1,4-diketones. The latter were converted in the key step, a bismuth-catalyzed ring transformation with methylamine, yielding the racemic eightmembered ring lactams, that is, tetrahydrothieno[2,3-c]-, [3,2-c]-, and -[3,4-c]azocine derivatives in overall yields of 25%, 16% and 12%, respectively.Some years ago, a new, elegant, and relatively simple route to prepare unsaturated 2-azocanone derivatives 1 (1,2,3,4,5,6-hexahydroazocin-2-ones, Figure 1) was discovered. 2 The reaction proceeded by a bismuth-catalyzed ringtransformation of five-membered ring oxo esters 4 containing a 1,4-diketone moiety 3 and primary amines R 1 NH 2 . Since these products 1 exist in a folded conformation, they represent an attractive molecular scaffold for combinatorial chemistry. In our continuing efforts to identify sophisticated structural motifs as a basis for combinatorial library synthesis in drug discovery, we are interested in such nonplanar and easily accessible scaffolds that provide several points of diversification. Such three-dimensional scaffolds open additional opportunities for adapting the shape of drug molecules to the requirements of binding sites on biological targets. Therefore, we have already explored scaffolds 1 as the basis of library synthesis. 4 Two points of diversity in structures 1 are the residues R 1 at N-1 and R 2 at C-8 originating from diketones 4 and primary amines, respectively. As an additional site for further diversifying functionalization (R 3 ) the carboxylate moiety at C-6 was selected, which could be converted with another amine R 3 NH 2 to carboxamides after saponification. As an extension of molecular diversity of the scaffold heterocyclic oxo esters were considered as starting materials, which resulted in thiazocane (X = S) 5 and diazocane (X = NR 4 ) 6 scaffolds 2 and 3. We have furthermore accessed benzo[c]-and pyrido[c]-annulated azocanes when starting with indane 7 and azaindane derivatives. 8 Compound 5 represents one of three regioisomeric pyrido[c]azocane motifs prepared by us. Figure 1 Some azocanones 1-3 and 5, precursor compound 4, and the antipsychotic drug olanzapine (6) N N R 2 R 1 O CONHR 3 5 X N R 2 R 1 O CONHR 3