The arimetamycin A glycan governs the compound’s cytotoxicity (IC 50 ). To study this branched, deoxy-amino disaccharide, we designed and synthesized a modified acyl donor that underwent glycosylation with three anthracycline aglycones: steffimycinone, daunorubicinone, and doxorubicinone. The result of the approach was a synthesis of arimetamycin A and two novel hybrid anthracyclines. Each molecule exhibited enhanced cytotoxicity in comparison to the parent anthracyclines, steffimycin B, daunorubicin, and doxorubicin. An orienting mechanistic evaluation revealed that the daunorubicin hybrid inhibits the ability of human topoisomerase IIα to relax negatively and positively supercoiled DNA.

Despite broad interest in metal carbene complexes, there remain few examples of catalytic transformations of ethers that proceed via alkoxycarbene intermediates generated by α,α-dehydrogenation. We demonstrate that both neutral and cationic alkoxycarbene derivatives are accessible via ether dehydrogenation at a PNP­(iPr)4 pincer-supported iridium complex (PNP­(iPr)4 = 2,6-bis­((diisopropylphosphino)­methyl)­pyridine). Both cationic and neutral alkoxycarbene complexes undergo group transfer imination with azides, with the cationic derivative serving as a more efficient catalyst for cyclopentyl ether imination. Mechanistic studies support an iridium­(I)­dinitrogen complex as the resting state in the dark and a role for light-promoted N2 dissociation. Isoamyl nitrite and phenyl ethyl ketene are also found to engage with the cationic alkoxycarbene complex in formal alkoxide and O atom transfer reactions, respectively. In the former case an isolable dialkoxyalkyliridium complex is obtained, representing only the second example of a structurally characterized dialkoxyalkyl complex of a transition metal.

Methyl tert-butyl ether is found to undergo C–O bond cleavage in the formation of an iridium­(III) methallyl at a cationic bis­(phosphine) iridium complex. An exploration of this transformation has revealed a cyclometalated complex which was previously postulated to form reversibly in the first example of alkane dehydrogenation by a homogeneous transition-metal complex. The competence of this cyclometalated species in alkane dehydrogenation is demonstrated in a stoichiometric example, giving an isolable olefin dihydride. Detection and assignment of this elusive species confirms a previous hypothesis that reversible intramolecular phosphine cyclometalation can precede intermolecular alkane dehydrogenation.

The intermolecular oxidative addition of unactivated C­(sp3)-Si bonds is reported for a family of organosilanes at a cationic pincer-supported iridium complex. To our knowledge, no examples of oxidative addition to give analogous unsupported (alkyl)metal silyl complexes have been previously reported. The generality of this transformation is excellent, with successful examples demonstrated for tetraorganosilanes, mono- and poly alkoxysilanes, and two siloxysilanes. Oxidative addition is found to be completely reversible, with the product of reductive elimination being subject to trapping by triethylsilane. The successful isolation of these metal silyl complexes has allowed for an in-depth kinetic analysis of C­(sp3)-Si reductive elimination, a process with strong implications in both catalytic C–H silylation and olefin hydrosilylation. The apparent order of reactivity is SiMe3 > SiMe2(CF3) > SiMe2OSiMe3 > SiMe2OSiMe2OSiMe3 > SiMe2(OMe) > SiMe2(OEt) > SiMe­(OMe)2. A DFT analysis of the oxidative addition products shows that the thermodynamic stability of the (alkyl)metal silyl complexes span a range of ca. 10 kcal·mol–1, which relate closely with the experimentally determined rates of C­(sp3)-Si reductive elimination and trapping, though a clear kinetic distinction exists between methoxy- and siloxysilyl complexes.

No abstract