Diversity Oriented Synthesis of Polycyclic Heterocycles through the Condensation of 2-Amino[1,2,4]triazolo[1,5-a]pyrimidines with 1,3-Diketones.

The acid-catalyzed condensation between 2-aminosubstituted [1,2,4]triazolo[1,5-a]pyrimidines and their analogues with various saturation of the pyrimidine ring and 1,3-diketones or 1,1,3,3-tetramethoxypropane was evaluated as a new approach for the synthesis of diversely substituted polycyclic derivatives of triazolopyrimidine. The reaction of 4,5,6,7-tetrahydro- or aromatic aminotriazolopyrimidines results in selective formation of the corresponding [1,2,4]triazolo[1,5-a:4,3-a']dipyrimidin-5-ium salts, and the condensation of substrates containing the 4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine fragment is accompanied by a cascade rearrangement with unusual recyclization of the dihydropyrimidine ring to yield partially hydrogenated [1,2,4]triazolo[1,5-a:4,3-a']dipyrimidin-5-ium or pyrimido[1',2':1,5][1,2,4]triazolo[3,4-b]quinazolin-5-ium salts. The proposed methodology exhibits a wide scope, providing rapid access to polycondensed derivatives of the [1,2,4]triazolo[1,5-a]pyrimidine scaffold. DFT calculations of the Gibbs free energies of possible isomers were performed to rationalize the experimentally observed reactivity and selectivity.

Revealing the unusual role of bases in activation/deactivation of catalytic systems: O-NHC coupling in M/NHC catalysis.

Numerous reactions are catalyzed by complexes of metals (M) with N-heterocyclic carbene (NHC) ligands, typically in the presence of oxygen bases, which significantly shape the performance. It is generally accepted that bases are required for either substrate activation (exemplified by transmetallation in the Suzuki cross-coupling), or HX capture (e.g. in a variety of C-C and C-heteroatom couplings, the Heck reaction, C-H functionalization, heterocyclizations, etc.). This study gives insights into the behavior of M(ii)/NHC (M = Pd, Pt, Ni) complexes in solution under the action of bases conventionally engaged in catalysis (KOH, NaOH, t-BuOK, Cs2CO3, K2CO3, etc.). A previously unaddressed transformation of M(ii)/NHC complexes under conditions of typical base-mediated M/NHC catalyzed reactions is disclosed. Pd(ii) and Pt(ii) complexes widely used in catalysis react with the bases to give M(0) species and 2(5)-oxo-substituted azoles via an O-NHC coupling mechanism. Ni(NHC)2X2 complexes hydrolyze in the presence of aqueous potassium hydroxide, and undergo the same O-NHC coupling to give azolones and metallic nickel under the action of t-BuOK under anhydrous conditions. The study reveals a new role of NHC ligands as intramolecular reducing agents for the transformation of M(ii) into "ligandless" M(0) species. This demonstrates that the disclosed base-mediated O-NHC coupling reaction is integrated into the catalytic M/NHC systems and can define the mechanism of catalysis (molecular M/NHC vs. "NHC-free" cocktail-type catalysis). A proposed mechanism of the revealed transformation includes NHC-OR reductive elimination, as implied by a series of mechanistic studies including 18O labeling experiments.