Dual cobalt – copper light-driven catalytic reduction of aldehydes and aromatic ketones in aqueous media

We present an efficient, general, fast, and robust light-driven methodology based on earth-abundant elements to reduce aryl ketones, and both aryl and aliphatic aldehydes (up to 1400 TON). The catalytic system consists of a robust and well-defined aminopyridyl cobalt complex active for photocatalytic water reduction and the [Cu(bathocuproine)(Xantphos)](PF6) photoredox catalyst. The dual cobalt–copper system uses visible light as the driving-force and H2O and an electron donor (Et3N or iPr2EtN) as the hydride source. The catalytic system operates in aqueous mixtures (80–60% water) with high selectivity towards the reduction of organic substrates (>2000) vs. water reduction, and tolerates O2. High selectivity towards the hydrogenation of aryl ketones is observed in the presence of terminal olefins, aliphatic ketones, and alkynes. Remarkably, the catalytic system also shows unique selectivity for the reduction of acetophenone in the presence of aliphatic aldehydes. The catalytic system provides a simple and convenient method to obtain α,β-deuterated alcohols. Both the observed reactivity and the DFT modelling support a common cobalt hydride intermediate. The DFT modelled energy profile for the [Co–H] nucleophilic attack to acetophenone and water rationalises the competence of [CoII–H] to reduce acetophenone in the presence of water. Mechanistic studies suggest alternative mechanisms depending on the redox potential of the substrate. These results show the potential of the water reduction catalyst [Co(OTf)(Py2Tstacn)](OTf) (1), (Py2Tstacn = 1,4-di(picolyl)-7-(p-toluenesulfonyl)-1,4,7-triazacyclononane, OTf = trifluoromethanesulfonate anion) to develop light-driven selective organic transformations and fine solar chemicals

Elementary Steps of Iron Catalysis: Exploring the Links between Iron Alkyl and Iron Olefin Complexes for their Relevance in C—H Activation and C—C Bond Formation

The alkylation of complexes 2 and 7 with Grignard reagents containing β-hydrogen atoms is a process of considerable relevance for the understanding of C–H activation as well as C–C bond formation mediated by low-valent iron species. Specifically, reaction of 2 with EtMgBr under an ethylene atmosphere affords the bis-ethylene complex 1 which is an active precatalyst for prototype [2+2+2] cycloaddition reactions and a valuable probe for mechanistic studies. This aspect is illustrated by its conversion into the bis-alkyne complex 6 as an unprecedented representation of a cycloaddition catalyst loaded with two substrates molecules. On the other hand, alkylation of 2 with 1 equivalent of cyclohexylmagnesium bromide furnished the unique iron alkyl species 11 with a 14-electron count, which has no less than four β-H atoms but is nevertheless stable at low temperature against β-hydride elimination. In contrast, the exhaustive alkylation of 1 with cyclohexylmagnesium bromide triggers two consecutive C–H activation reactions mediated by a single iron center. The resulting complex has a diene dihydride character in solution (15), whereas its structure in the solid state is more consistent with an η3-allyl iron hydride rendition featuring an additional agostic interaction (14). Finally, the preparation of the cyclopentadienyl iron complex 25 illustrates how an iron-mediated C–H activation cascade can be coaxed to induce a stereoselective C—C bond formation. The structures of all relevant new iron complexes in the solid state are presented

Mechanistic Elucidation of the Arylation of Non-Spectator N-Heterocyclic Carbenes at Copper Using a Combined Experimental and Computational Approach

CuI(NHC)Br complexes (NHC = N-heterocyclic carbene) undergo a direct reaction with iodobenzene to give 2-arylated benzimidazolium products. The nature of the N-substituent on the NHC ligand influences the reactivity of the CuI(NHC)Br complex toward arylation. N-Benzyl or N-phenyl substituents facilitate arylation, whereas N-mesityl substituents hinder arylation. Density functional theory calculations show that an oxidative addition/reductive elimination pathway involving CuIII species is energetically feasible. A less hindered CuI(NHC)Br complex with N-benzyl groups is susceptible to oxidation reactions to give 1,3-dibenzylbenzimidazolium cations containing a CuIBr anion (various polymorphs). The results described herein are of relevance to C–H functionalization of (benz)azoles

Ligand Exchange on and Allylic C−H Activation by Iron(0) Fragments: π‑Complexes, Allyliron Species, and Metallacycles

The complexes [(dippp)Fe(C2H4)2] (2) and [CpFe(C2H4)2][Li·(tmeda)] (5) both contain a formally zerovalent iron center but exhibit markedly different catalytic properties. Whereas 5 is able to induce a broad range of cycloisomerization and cycloaddition reactions, 2 is so far basically limited to cyclotrimerizations of alkynes and nitriles. Investigations into the behaviors of both complex vis-à-vis unsaturated substrates provided insights into the likely origins of this distinct behavior. Thus, ordinary terminal or internal alkenes were found not to replace the ligated ethylene units in 2, whereas the stronger π-acceptor ligands 1,5-cyclooctadiene, 2- norbornene, and tolane afforded the corresponding π-complexes 8, 9, 10, and 13. A cyclopropene derivative engaged in oxidative cyclization with formation of the corresponding metallacycle 12. Allyl-9-BBN or alkenyl-9-BBN derivatives succumbed to allylic C−H activation with formation of the unorthodox allyliron complexes 25 and 27 featuring a bridging hydride ligand between the iron and the boron atoms. Along the same line, 1,3-dienes bind well to 2 but undergo spontaneous activation if allylic C−H bonds are present; the resulting hydride is transferred to a residual ethylene ligand, as manifest in the formation of the cyclopentadienyl ethyl complex 22. The same elementary steps surface in a remarkable reaction cascade comprising two consecutive C−H activation reactions and a stereoselective C−C bond formation, which ultimately provides the substituted cyclohexadienyl complexes 20 and 23. In contrast, the heterobimetallic complex 5 neither induces allylic C−H activation nor binds 1,3-butadiene under conditions where it proved catalytically active. The targeted butadiene complex 34 had to be made by an indirect route and is distinguished by a noteworthy "flyover" constitution. Therefore, we conclude that the known cycloaddition and cycloisomerization reactions catalyzed by 5 do not commence at a 1,3-diene motif but require an enyne entity as starter unit

Two Exceptional Homoleptic Iron(IV) Tetraalkyl Complexes

The formation of the high-valent iron complex [Fe(cyclohexyl)₄] from Fe^II under reducing conditions is best explained by disproportionation of a transient organoiron intermediate which is driven by dispersive forces between the cyclohexyl ligands and the formation of short and strong Fe−C bonds. The (meta)stability of this diamagnetic complex (S=0) is striking if one considers that it has empty d-orbitals at its disposal and contains, at the same time, no less than twenty H-atoms available for either α- or β-hydride elimination

Obstructive Sleep Apnea Monocytes Exhibit High Levels of Vascular Endothelial Growth Factor Secretion, Augmenting Tumor Progression

Obstructive sleep apnea (OSA) is a syndrome characterized by repeated pauses in breathing induced by a partial or complete collapse of the upper airways during sleep. Intermittent hypoxia (IH), a hallmark characteristic of OSA, has been proposed to be a major determinant of cancer development, and patients with OSA are at a higher risk of tumors. Both OSA and healthy monocytes have been found to show enhanced HIF1α expression under IH. Moreover, these cells under IH polarize toward a tumor-promoting phenotype in a HIF1α-dependent manner and influence tumor growth via vascular endothelial growth factor (VEGF). Monocytes from patients with OSA increased the tumor-induced microenvironment and exhibited an impaired cytotoxicity in a 3D tumor in vitro model as a result of the increased HIF1α secretion. Adequate oxygen restoration both in vivo (under continuous positive airway pressure treatment, CPAP) and in vitro leads the monocytes to revert the tumor-promoting phenotype, demonstrating the plasticity of the innate immune system and the oxygen recovery relevance in this context