Activation of H-H, HO-H, C(sp2)-H, C(sp3)-H, and RO-H bonds by transition-metal frustrated lewis pairs based onon M/N (M = Rh, Ir) couples

Reaction of the dimers (Cp*MCl)2(µ-Cl)2] (Cp* = 5-C5Me5) with Ph2PCH2CH2NC(NH(p-Tolyl))2 (H2L) in the presence of NaSbF6 affords the chlorido complexes Cp*MCl(¿2N, P-H2L)]SbF6] (M = Rh, 1; Ir, 2). Upon treatment with aqueous NaOH, solutions of 1 and 2 yield the corresponding complexes Cp*M(¿3N, N', P-HL)]SbF6] (M = Rh, 3; Ir, 4) in which the ligand HL presents a fac ¿3N, N', P coordination mode. Treatment of THF solutions of complexes 3 and 4 with hydrogen gas, at room temperature, results in the formation of the metal hydrido-complexes Cp*MH(¿2N, P-H2L)]SbF6] (M = Rh, 5; Ir, 6) in which the N(p-Tolyl) group has been protonated. Complexes 3 and 4 react with deuterated water in a reversible fashion resulting in the gradual deuteration of the Cp* group. Heating at 383 K THF/H2O solutions of the complexes 3 and 4 affords the orthometalated complexes Cp*M(¿3C, N, P-H2L-H)]SbF6] M = Rh, 7; Ir, 8, H2L-H = Ph2PCH2CH2NC(NH(p-Tolyl))(NH(4-C6H3Me))], respectively. At 333 K, complexes 3 and 4 react in THF with methanol, primary alcohols, or 2-propanol giving the metal-hydrido complexes 5 and 6, respectively. The reaction involves the acceptorless dehydrogenation of the alcohols at a relatively low temperature, without the assistance of an external base. The new complexes have been characterized by the usual analytical and spectroscopic methods including the X-ray diffraction determination of the crystal structures of complexes 1-5, 7, and 8. Notably, the chlorido complexes 1 and 2 crystallize both as enantiopure conglomerates and as racemates. Reaction mechanisms are proposed based on stoichiometric reactions, nuclear magnetic resonance studies, and X-ray crystallography as well as density functional theory calculations. © 2022 The Authors. Published by American Chemical Society

Synthesis and Characterization of Zwitterionic Metallates and Molecular Clusters

This thesis reports the synthesis and characterization of novel zwitterionic metallates of Rh and Pd with the ligand EtNHC(S)PPh2=NPPh2C(S)NEt (HEtSNS). This ligand is an amphoteric zwitterion, which forms the H2EtSNS+ cation upon protonation and the EtSNS- dianion–cation upon deprotonation. Determination of absolute pKa in CH2Cl2 by a spectrophotometric titration and kinetic/thermodynamic studies of the oxidative addition of methyl iodide to the zwitterionic metallate complex [Rh(CO)EtSNS] and its derivatives obtained by protonation: [Rh(CO)EtSNS]·HA and [Rh(CO)EtSNS]·2HA, where A = PF6, OTf, NO3 by 1H NMR spectroscopy are discussed. The reaction of the zwitterionic ligand with [Ru3(CO)12] affords an unprecedented methideylamide –N(Et)CH(R)– μ3-bridging moiety. Finally, enchainment cooperativity effects in neutrally charged bimetallic Nickel (II) phenoxyiminato polymerization catalysts and enhanced selectivity for polar comonomer are reported

Studies on Oximidine II - Total Synthesis by an Unprecedented Reductive Coupling

The benzolactone enamide natural products are identified by three structural characteristics: a salicylate arene, a 12- or 15-membered macrolactone, and an enamide side chain. These natural products exert their biological activity by inhibiting the vacuolar-(H+)-ATPase (V-ATPase) enzyme. The benzolactone enamide oximidine II has been synthesized twice previously with only moderate yields realized for the key macrocyclization step. Following a previous Georg group strategy, we envisioned performing the ring-closure using a Castro-Stephens reaction. While optimizing this copper-mediated macrocyclization, we discovered an unprecedented copper-mediated reductive coupling reaction. The enamide side chain of these natural products is postulated to be critical for biological activity. To probe the importance of this acid-sensitive moiety, we synthesized an allylic amide homolog of oximidine II and tested both oximidine II and this analog in melanoma cancer cells. The bacterial enzyme UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) catalyzes the first committed step of cell wall biosynthesis. Using highthroughput screening, 5 scaffolds were identified with MurA inhibitory activity. Analog development of the pyrrole-benzoic acid scaffold failed to generate compounds with improved potency. We then turned to structure-based drug design to investigate new MurA inhibitors. Using computer-modeling software, low molecular weight molecules were docked into various MurA crystal structures. Evaluation of these docking studies revealed 4 small molecules as potential leads for further optimization. Dioxins are environmental pollutants that cause a range of biological effects in a dose-dependent manner. The exact mechanism of action for dioxins is not fully understood. 2,3,7,8-Tetrachlorophenothiazine (TCPT) was designed to probe potential mechanisms of action and biological effects of dioxin analogs. Utilization of Buchwald-Hartwig coupling methodology produced TCPT in 37% yield. Preliminary biological testing of TCPT has shown favorable pharmacokinetic properties