Metal-mediated coupling between one or two isonitrile ligands in cis-[MCl 2 (CtNR) 2 ] [M = Pd, Pt; R = 2,6-Me 2 C 6 H 3 (Xyl), Bu t , cyclohexyl (Cy)] and N-phenylbenzamidine, HNdC(Ph)NHPh, proceeds with different regioselectivity upon varying R group. When the aromatic isonitrile is used (R = Xyl), N-phenylbenzamidine is coordinated to a metal by the HNdC moiety, and the nucleophilic attack proceeds via the NHPh center of the benzamidine giving [MCl{C(N(Ph)C(Ph)dNH)d NXyl}(CtNXyl)]. For R = Bu t , HNdC(Ph)NHPh is coordinated to a metal by the NHPh center, and the addition occurs via the HNdC center of the nucleophile to afford [MCl{C(NC(Ph)dNPh)d NBu t }(CtNBu t )]. With R = Cy, a mixture of two products that are derived from the addition of N-phenylbenzamidine by two nucleophilic centers was detected. The substituent R dependent reactivity was explored using theoretical (DFT) methods and interpreted as a result of the steric repulsions in one of the regioisomers of the addition products, when R = Cy and Bu t . All prepared species were fully characterized by elemental analyzes (C, H, N), high resolution ESI þ -MS, IR, 1D

An efficient strategy for the synthesis of asymmetrically substituted enediynes fused to benzothiophene, benzofuran, and indole was developed. The proposed approach is based on the electrophilic cyclization of diacetylenes and Sonogashira coupling. Thus, iodocyclization of readily available ortho-functionalized (buta-1,3-diynyl)arenes was used as a direct way for the synthesis of 2-ethynyl-3-iodoheteroindenes. These substrates and their modified derivatives were easily converted by Sonogashira coupling with acetylenes to a variety of asymmetrically substituted acyclic enediynes fused to heterocycles. The tolerance of the developed methodology to a variety of functional groups is a great advantage in the synthesis of macrocyclic enediyne systems fused to a heterocyclic core. Synthesis of indole-fused 12-membered macrocyclic dienediyne was achieved using ring-closing metathesis as a key step.

The Nicholas‐type macrocyclization has been used for the first time for the synthesis of 10‐ and 11‐membered oxaenediynes fused to a benzothiophene. The acyclic starting materials were easily synthesized by electrophilic cyclization of o‐(buta‐1,3‐diynyl)thioanisoles followed by a Sonogashira coupling of the resulting 2‐ethynyl‐3‐iodobenzothiophenes with functionalized alkynes. A high reactivity of the 10‐membered oxacycles in the Bergman cyclization was predicted by DFT calculations and confirmed by differential scanning calorimetry. The ability of enediynes to induce single‐strand PM2 DNA scissions was also found.

Reactions of [H 2 Os 3 (CO) 10 ] with the substituted diynes R-C 5), and {µ-η 1 :η 1 -CH 3 CCdC-C(H)dC(H)-NPh} (6), which have been characterized by single-crystal X-ray diffraction analyses as well as by various spectroscopic methods. In clusters 4-6, the starting diynes 1-3 have been rearranged to form substituted pyrrolyl rings which bridge two osmium atoms in η 1 :η 2 -(4, 5) or η 1 :η 1 -(6) coordination modes depending on the nature of substituents in 1-3. A possible reaction pathway for the diyne cyclization reactions that yield 4-6 involves initial transfer of a hydride onto a coordinated diyne followed by a series of 1,3-shifts and subsequent nucleophilic attack of the nitrogen on the third carbon atom of the diyne system to afford the five-membered pyrrolyl ring. Cluster 6 and its previously characterized furanyl analogue [HOs 3 (CO) 10 {µ-η 1 :η 1 -(OCH-CHCC)-C-CH 3 )}] (7) undergo facile thermal transformation accompanied by the loss of a CO ligand to give the clusters [HOs 3 (CO) 9 {µ 3 ,η 3 -CH 3 CCdC-C(H)dC(H)-NPh}] (8) and [HOs 3 (CO) 9 {µ 3 ,η 3 -(OCHdCHCdCCCH 3 )}] (9). In both 8 and 9, single-crystal X-ray analysis revealed the presence of pentagonal pyramid cluster cores containing three osmium and three carbon atoms.

Immobilization of palladium­(II) acyclic diaminocarbene (Pd­(II)-ADC) complexes on a resin support surface has been easily performed by metal-mediated addition of amino groups of benzhydrylamine-polystyrene to the coordinated isocyanide ligand of cis-PdCl2(CNR)2 (R = t-Bu, Cy). The investigation of the benzhydrylamine reaction with palladium-coordinated isocyanides in solution has revealed that, depending on the reaction conditions, two carbene-type complexes can be obtained as a result of the addition to the CN triple bond, as well as a third complex which is formed via substitution of the isocyanide ligand by benzhydrylamine. Nucleophilic addition of an amino group to the isocyanide ligand has led to a cis-acyclic diaminocarbene complex or a cationic diaminocarbene complex with trans configuration and an intramolecular hydrogen-bonded chloride anion (the nature of this noncovalent interaction was analyzed by DFT calculations, including AIM analysis). The unsupported and resin-supported palladium catalysts have demonstrated high catalytic activity in both Sonogashira and Suzuki–Miyaura cross-coupling. The supported catalyst can be recovered and repeatedly reused without a significant loss in efficiency. The degree of the palladium binding with polystyrene, the oxidation state, and the palladium leaching level were investigated by XPS and XRF analyses.

Cu-catalyzed 1,3-dipolar cycloaddition of iododiacetylenes with organic azides using iodotris­(tri­phenyl­phos­phine)­copper­(I) as a catalyst was found to be an efficient one-step synthetic route to 5-iodo-4-ethynyltriazoles. The reaction is tolerant to various functional groups in both butadiyne and azide moieties. The synthetic application of 5-iodo-4-ethynyl triazoles obtained was also evaluated: the Sonogashira coupling with alkynes resulted in unsymmetrically substituted triazole-fused enediyne systems, while the Suzuki reaction yielded the corresponding 5-aryl-4-ethynyl triazoles.

To find promising analogues of naturally occurring enediyne antibiotics with a sufficient reactivity in the Bergman cyclization and moderately stable under isolation and storage, a scale of relative enediynes reactivity was created on the basis of calculated free activation energies for the Bergman cyclization within 12 known and new benozothiophene, benzene, and cinnoline annulated 9- and 10-membered enediynes. To verify the predicted reactivity/stability balance, three new carbocyclic enediynes fused to a benzothiophene core bearing 3,4,5-trimethoxybenzene, fluoroisopropyl, and isopropenyl substituents were synthesized using the Nicholas-type macrocyclization. It was confirmed that annulation of a 3,4,5-trimethoxybenzene moiety to a 10-membered enediyne macrocycle imparts high reactivity to an enediyne while also conferring instability under ambient temperature. Fluoroisopropyl-substituted 10-membered enediyne from the opposite end of the scale was found to be stable while moderately reactive in the Bergman cyclization. Along with the experimentally confirmed moderate reactivity (DSC kinetic studies), (fluoroisopropyl)enediyne showed a significant DNA damaging activity in plasmid cleavage assays comparable with the known anticancer drug Zeocin.

A short and efficient synthesis of cinnoline-fused cyclic enediyne is reported. Richter cyclization of o-(1,3-butadiynyl)phenyltriazene produced 3-alkynyl-4-bromocinnoline. The Sonogashira coupling of the latter with 5-hexyn-1-ol was employed for the introduction of a second acetylenic moiety. The crucial cyclization step was achieved under Nozaki-Hiyama-Kishi conditions. Cinnoline-fused 10-membered ring enediyne is more reactive than corresponding carbocyclic analog and produces good yield of the Bergman cyclization product upon mild heating. This enediyne induces single-strand dDNA scissions upon incubation at 40 °C.