Effects of Ionic Liquids on the Thermodynamics of Hydrogen Activation by Frustrated Lewis Pairs: A Density Functional Theory Study**

Nowadays, hydrogen activation by frustrated Lewis pairs (FLPs) and their applications are one of the emerging research topics in the field of catalysis. Previous studies have shown that the thermodynamics of this reaction is determined by electronic structures of FLPs and solvents. Herein, we investigated systems consisting of typical FLPs and ionic liquids (ILs), which are well known by their large number of types and excellent solvent effects. The density functional theory (DFT) calculations were performed to study the thermodynamics for H₂ activation by both inter- and intra-molecular FLPs, as well as the individual components. The results show that the computed overall Gibbs free energies in ILs are more negative than that computed in toluene. Through the thermodynamics partitioning, we find that ILs favor the H−H cleavage elemental step over the elemental steps of proton attachment, hydride attachment and zwitterionic stabilization. Moreover, the results show that these effects are strongly dependent on the type of FLPs, where intra-molecular FLPs are more affected compared to the inter-molecular FLPs.     

Molecularly engineering polymeric membranes for H2/CO2 separation at 100–300 °C

Over the last two decades, polymers with superior H₂/CO₂ separation properties at 100–300 °C have gathered significant interest for H₂ purification and CO₂ capture. This timely review presents various strategies adopted to molecularly engineer polymers for this application. We first elucidate the Robeson's upper bound at elevated temperatures for H₂/CO₂ separation and the advantages of high-temperature operation (such as improved solubility selectivity and absence of CO₂ plasticization), compared with conventional membrane gas separations at ~35 °C. Second, we describe commercially relevant membranes for the separation and highlight materials with free volumes tuned to discriminate H₂ and CO₂, including functional polymers (such as polybenzimidazole) and engineered polymers by cross-linking, blending, thermal treatment, thermal rearrangement, and carbonization. Third, we succinctly discuss mixed matrix materials containing size-sieving or H₂-sorptive nanofillers with attractive H₂/CO₂ separation properties.     

Gapmer Antisense Oligonucleotides Containing 2′,3′-Dideoxy-2′-fluoro-3′-C-hydroxymethyl-β-d-lyxofuranosyl Nucleotides Display Site-Specific RNase H Cleavage and Induce Gene Silencing

Off-target effects remain a significant challenge in the therapeutic use of gapmer antisense oligonucleotides (AONs). Over the years various modifications have been synthesized and incorporated into AONs, however, precise control of RNase H-induced cleavage and target sequence selectivity has yet to be realized. Herein, the synthesis of the uracil and cytosine derivatives of a novel class of 2′-deoxy-2′-fluoro-3′-C-hydroxymethyl-β-d -lyxo-configured nucleotides has been accomplished and the target molecules have been incorporated into AONs. Experiments on exonuclease degradation showed improved nucleolytic stability relative to the unmodified control. Upon the introduction of one or two of the novel 2′-fluoro-3′-C-hydroxymethyl nucleotides as modifications in the gap region of a gapmer AON was associated with efficient RNase H-mediated cleavage of the RNA strand of the corresponding AON:RNA duplex. Notably, a tailored single cleavage event could be engineered depending on the positioning of a single modification. The effect of single mismatched base pairs was scanned along the full gap region demonstrating that the modification enables a remarkable specificity of RNase H cleavage. A cell-based model system was used to demonstrate the potential of gapmer AONs containing the novel modification to mediate gene silencing.     

Transition-Metal-Free Multiple Functionalization of Piperidines to 4-Substituted and 3,4-Disubstituted 2-Piperidinones

Remote and multiple functionalization of piperidines without the use of transition-metal catalysts and elaborate directing groups is one of the major challenges in organic synthesis. Herein is reported an unprecedented two-step protocol that enables the multiple functionalization of piperidines to either 4-substituted or trans-3,4-disubstituted 2-piperidones. First, by exploiting the duality of TEMPO reactivity, which under oxidative and thermal conditions fluctuates between cationic and persistent-radical form, a novel multiple C(sp³)-H oxidation of piperidines to α,β-unsaturated 2-piperidones was developed. Second, the intrinsic low reactivity of the unsaturated piperidones toward conjugated Grignard additions was overcome by using trimethylsilyl chloride (TMSCl) as Lewis acid. Subsequently, conjugated Grignard addition/electrophilic trapping protocol provided substituted 2-piperidone intermediates, some of which were then transformed into pharmaceutical alkaloids.     

Electrophotocatalytic Undirected C−H Trifluoromethylations of (Het)Arenes

Electrophotochemistry has enabled arene C−H trifluoromethylation with the Langlois reagent CF₃SO₂Na under mild reaction conditions. The merger of electrosynthesis and photoredox catalysis provided a chemical oxidant-free approach for the generation of the CF₃ radical. The electrophotochemistry was carried out in an operationally simple manner, setting the stage for challenging C−H trifluoromethylations of unactivated arenes and heteroarenes. The robust nature of the electrophotochemical manifold was reflected by a wide scope, including electron-rich and electron-deficient benzenes, as well as naturally occurring heteroarenes. Electrophotochemical C−H trifluoromethylation was further achieved in flow with a modular electro-flow-cell equipped with an in-operando monitoring unit for on-line flow-NMR spectroscopy, providing support for the single electron transfer processes.     

Cobalt(II)-Catalyzed [4+2] Annulation of Picolinamides with Alkynes via C−H Bond Activation

A cobalt(II)-catalyzed [4+2] annulation of picolinamides with alkynes via C−H bond activation has been developed. The operationally simple annulation reaction allows for the synthesis of acyl-substituted 1H-benzoquinoline bearing multiple aromatic rings (up to 96 % yield) without co-oxidant or other oxidation factors under mild conditions. Several control experiments were carried out. This practical [4+2] annulation provides an efficient route to access highly functionalized compounds.     

Iridium-Catalyzed Regioselective B(3)-Alkenylation/B(3,6)-Dialkenylation of o-Carboranes by Direct B−H Activation

Iridium-catalyzed formal alkyne hydroboration with cage B−H of o-carborane has been achieved, leading to the controlled synthesis of a series of 3,6-[trans-(AlkCH=CH)]₂-o-carboranes (Alk=alkyl), 3-cis-(ArCH=CH)-o-carboranes (Ar=aryl), and 3-cis-(ArCH=CH)-6-trans-(AlkCH=CH)-o-carboranes in high yields with excellent regio- and very good cis–trans selectivity. The most electron-deficient B(3,6)−H vertices favor oxidative addition on electron-rich metal centers, which is responsible for the regioselectivity. On the other hand, the configuration of the resultant olefinic units is dominated by alkyne substituents. Alkyl groups lead to a trans-configuration whereas bulky aryl substitutions result in cis-configuration.     

RhIII-Catalyzed Double Dehydrogenative Coupling of Free 1-Naphthylamines with α,β-Unsaturated Esters

The Rh^III-catalyzed, consecutive double C−H oxidative coupling of free 1-naphthylamine and α,β-unsaturated esters through C−H/C−H and C−H/N−H bonds is reported. The one step reaction leads to the formation of biologically important alkylidene-1,2-dihydrobenzo[cd]indoles scaffolds. This efficient process is much more synthetically convenient and useful than others because the starting materials, such as 1-naphthylamine derivatives are readily available and the free amine serves as a directing group.     

Rhodium(III)-Catalyzed C−H/N−H Functionalization with Hydrogen Evolution

A rhodium(III)-catalyzed C−H/N−H bond functionalization of benzimidates with α-chloroaldehydes to afford isoquinolin-3-ol derivatives is reported. No external oxidants are needed in this process, and interestingly, evolution of hydrogen gas is observed.     

Cobalt-Catalyzed Intramolecular Hydroacylation Involving Cyclopropane Cleavage

A simple cobalt-diphosphine catalyst has been found to efficiently promote intramolecular cyclization of ortho-cyclopropylvinyl- and cyclopropylidenemethyl-substituted benzaldehydes into benzocyclooctadienone and benzocycloheptadienone derivatives, respectively. This ring-opening hydroacylation likely involves aldehyde C−H oxidative addition, olefin insertion, cyclopropane cleavage by β-carbon elimination, and C−C bond-forming reductive elimination, as was supported by mechanistic experiments and DFT calculations.