Ongoing EEG artifact correction using blind source separation.

OBJECTIVE: Analysis of the electroencephalogram (EEG) for epileptic spike and seizure detection or brain-computer interfaces can be severely hampered by the presence of artifacts. The aim of this study is to describe and evaluate a fast automatic algorithm for ongoing correction of artifacts in continuous EEG recordings, which can be applied offline and online. METHODS: The automatic algorithm for ongoing correction of artifacts is based on fast blind source separation. It uses a sliding window technique with overlapping epochs and features in the spatial, temporal and frequency domain to detect and correct ocular, cardiac, muscle and powerline artifacts. RESULTS: The approach was validated in an independent evaluation study on publicly available continuous EEG data with 2035 marked artifacts. Validation confirmed that 88% of the artifacts could be removed successfully (ocular: 81%, cardiac: 84%, muscle: 98%, powerline: 100%). It outperformed state-of-the-art algorithms both in terms of artifact reduction rates and computation time. CONCLUSIONS: Fast ongoing artifact correction successfully removed a good proportion of artifacts, while preserving most of the EEG signals. SIGNIFICANCE: The presented algorithm may be useful for ongoing correction of artifacts, e.g., in online systems for epileptic spike and seizure detection or brain-computer interfaces.

An Iridium/Aluminum Cooperative Strategy for the ß-C(sp3 )-H Borylation of Saturated Cyclic Amines.

Despite the widespread success in the functionalization of C(sp2 )-H bonds, the deliberate functionalization of C(sp3 )-H bonds in a highly site- and stereoselective manner remains a longstanding challenge. Herein, we report an iridium/aluminum cooperative catalytic system that enables the ß-selective C-H borylation of saturated cyclic amines and lactams. Furthermore, we have accomplished an enantioselective variant using binaphthol-derived chiral aluminum catalysts to forge C-B bonds with high levels of stereocontrol. Computational studies suggest that the formation of a Lewis pair with the substrates is crucial to lower the energy of the transition state for the rate-determining reductive elimination step.

The Kumada-Tamao-Corriu Coupling Reaction Catalyzed by Rhodium-Aluminum Bimetallic Complexes.

Rhodium-aluminum bimetallic complexes catalyze the Kumada-Tamao-Corriu (KTC) cross-coupling reaction using arylmagnesium compounds that are generated from the corresponding aryl fluorides or chlorides in situ by these catalysts. This method allows the challenging KTC coupling reaction to be carried out using aryl fluorides as nucleophiles, which affords various biaryls.

Cross-Coupling Reactions of Nitroarenes.

Cross-coupling reactions are powerful synthetic tools to construct diverse chemical bonds often found in, for example, advanced materials and pharmaceuticals. Since their discovery, haloarenes have habitually been used as electrophilic coupling partners both in academic and industrial contexts. However, concerning the efficiency and the often-negative environmental impact of haloarene-based cross-coupling processes, more readily available, inexpensive, and environmentally friendly electrophiles have been explored.Nitroarenes, for example, are obtained from the facile nitration of aromatic compounds and, thus, represent one of the most easy-to-access feedstock electrophiles. Furthermore, their electron-deficient arene core can be functionalized easily and site-selectively through a wide variety of reactions. Yet, despite these advantages and even though the direct transformation of the NO2 group would be an attractive option in cross-coupling chemistry, it has so far remained difficult to convert nitroarenes via a cleavage of the Ar-NO2 bond given the inherent reactivity (or the lack thereof) of the nitro group. Such denitrative conversion has been performed by a conventional sequence of reduction, diazotization, and Sandmeyer reactions, which severely lacks efficiency and generality.This Account summarizes our recent research progress on cross-coupling reactions that employ nitroarenes as electrophiles. First, we developed the Suzuki-Miyaura coupling of nitroarenes using a palladium/BrettPhos catalyst. This reaction proceeds via an (at the time) unprecedented oxidative addition of the Ar-NO2 bond, which was supported by experimental results and theoretical calculations. A widely accepted catalytic cycle for Pd-catalyzed cross-couplings has since been extended to include nitroarenes as electrophiles, which significantly increases substrate generality. Second, this denitrative coupling protocol was applied to various bond-forming reactions, namely, Buchwald-Hartwig amination, etherification, and hydrogenation reactions. Such diversification has enhanced the utility of nitroarenes as cross-coupling partners. To develop each reaction, it was necessary to modify the reaction conditions as required to overcome the obstacles deriving from nitro functionality including transmetalation and side reactions, as well as oxidative addition. Third, we designed a new Pd/NHC catalyst that exhibits higher activity than Pd/BrettPhos. The improved performance of Pd/NHC system was supported by its strong electron-donicity and structural robustness, and it allows the reduction of the catalyst loading significantly, thus increasing the efficacy and practicality of this method.The field of nitroarene-based cross-coupling has just started to flourish. In addition to our original work, several research groups have already adopted Pd/BrettPhos or Pd/NHC catalysts to develop new denitrative functionalizations. The utility of nitroarenes in the context of organic synthesis should be now revisited.

C2-Selective silylation of pyridines by a rhodium-aluminum complex.

We have developed a C2-selective mono-silylation of a variety of pyridines using a Rh-Al complex. Both the site- and mono-selectivity are controlled via the pyridine coordination to the Lewis-acidic Al center prior to the activation of the pyridine C(2)-H bond at the proximal Rh center. A reaction mechanism is proposed based on several mechanistic studies, including the isolation of a (2-pyridyl)silylrhodium intermediate.

Selective C-O Bond Reduction and Borylation of Aryl Ethers Catalyzed by a Rhodium-Aluminum Heterobimetallic Complex.

We report the catalytic reduction of a C-O bond and the borylation by a rhodium complex bearing an X-type PAlP pincer ligand. We have revealed the reaction mechanism based on the characterization of the reaction intermediate and deuterium-labeling experiments. Notably, this novel catalytic system shows steric-hindrance-dependent chemoselectivity that is distinct from conventional Ni-based catalysts and suggests a new strategy for selective C-O bond activation by heterobimetallic catalysis.

Merging Pd0 /PdII Redox and PdII /PdII Non-redox Catalytic Cycles for the Allylarylation of Electron-Deficient Alkenes.

An allylarylation of electron-deficient alkenes with aryl boronates and allylic carbonates has been developed. This method allows access to a wide variety of carbon skeletons from readily available starting materials. Mechanistic studies indicate that this reaction is enabled by a cooperative catalysis based on merging Pd0 /PdII redox and PdII /PdII non-redox catalytic cycles.

Metal-mediated C-CN Bond Activation in Organic Synthesis.

Nitriles are ubiquitous versatile building blocks in organic synthesis. Common reactions of nitriles include the transformation of cyano groups into carbonyl and amine moieties. The functionalization of nitriles can also be accomplished at the alpha-position of alkanenitriles and at the ortho-position of cyanoarenes. On the other hand, the C-CN bond of nitriles has rarely been recognized as a valuable reaction site due to its thermodynamic robustness. Although it has been known for a long time in organometallic chemistry that C-CN bonds can be cleaved by transition-metal complexes, this elemental reaction had not been used in catalytic synthetic transformations of nitriles until two decades ago. This review surveys the progress of metal-catalyzed reactions of nitriles via C-CN bond activation. After introducing several different modes to activate C-CN bonds by various transition metals, catalytic reactions are categorized mainly into two parts: (i) reactions with CN as a leaving group and (ii) reactions with nitriles as a source of CN groups. Cross-coupling-type transformations with a cyano leaving group, cyanation reactions using nitriles as a nontoxic cyano source, and novel synthetic reactions such as carbocyanation are highlighted together with useful demonstrations of their utility in organic synthesis.

Coordination Flexibility of the Rh(PXP) Complex to NH3, CO, and C2H4 (PXP = Diphosphine-Based Pincer Ligand; X = B, Al, and Ga): Theoretical Insight.

The recently synthesized rhodium-aluminum bimetallic complex Rh(PAlP) 1 (PAlP = pincer-type diphosphino-aluminyl ligand Al{[N(C6H4)]2NMe}[CH2P(iPr)2]2) containing a unique Rh-Al direct bond exhibits coordination flexibility because Rh and Al can play the role of coordination site for the substrate. DFT calculations of NH3, CO, and C2H4 adducts with 1 show that the Rh atom is favorable for all these substrate but the Al atom is as favorable as the Rh atom for NH3 and unfavorable for CO and C2H4. NH3 and CO prefer the coordination at the Rh-axial (Ax) site to the Rh-equatorial (Eq) site, but C2H4 prefers coordination at the Rh-Eq site to the Rh-Ax site. Consequently, two CO and C2H4 molecules coordinate with 1 at the Rh-Ax and Rh-Eq sites to afford trigonal bipyramidal complexes Rh(PAlP)(CO)2 and Rh(PAlP)(C2H4)2, which is consistent with the experimental observation of Rh(PAlP)(CO)2. Energy decomposition analysis reveals that an electrostatic term plays an important role for NH3 coordination with the Al atom of 1, because Al has a significantly large positive charge and NH3 has a much negatively charged N atom and exhibits a considerably negative electrostatic potential at the Al position. In B and Ga analogues Rh(PBP) 2 and Rh(PGaP) 3, B and Ga atoms are not good for CO and C2H4 like the Al atom in 1. NH3 adducts with 2 and 3 at the B and Ga sites are less stable than those adducts at the Rh-Ax site unlike the NH3 adduct with 1 at the Al site. This difference in the NH3 adduct between Rh(PAlP) and others (Rh(PBP) and Rh(PGaP)) arises from much less positive charges of B and Ga and a smaller atomic size of B than that of Al. These results indicate that the significantly large electropositive nature and appropriate atomic size of Al are responsible for the characteristic coordination flexibility of Rh(PAlP).

Magnesiation of Aryl Fluorides Catalyzed by a Rhodium-Aluminum Complex.

We report the magnesiation of aryl fluorides catalyzed by an Al-Rh heterobimetallic complex. We show that the complex is highly reactive to cleave the C-F bonds across the polarized Al-Rh bond under mild conditions. The reaction allows the use of an easy-to-handle magnesium powder to generate a range of arylmagnesium reagents from aryl fluorides, which are conventionally inert to such metalation compared with other aryl halides.

Nickel-catalysed anti-Markovnikov hydroarylation of unactivated alkenes with unactivated arenes facilitated by non-covalent interactions.

Anti-Markovnikov additions to alkenes have been a longstanding goal of catalysis, and anti-Markovnikov addition of arenes to alkenes would produce alkylarenes that are distinct from those formed by acid-catalysed processes. Existing hydroarylations are either directed or occur with low reactivity and low regioselectivity for the n-alkylarene. Herein, we report the first undirected hydroarylation of unactivated alkenes with unactivated arenes that occurs with high regioselectivity for the anti-Markovnikov product. The reaction occurs with a nickel catalyst ligated by a highly sterically hindered N-heterocyclic carbene. Catalytically relevant arene- and alkene-bound nickel complexes have been characterized, and the rate-limiting step was shown to be reductive elimination to form the C-C bond. Density functional theory calculations, combined with second-generation absolutely localized molecular orbital energy decomposition analysis, suggest that the difference in activity between catalysts containing large and small carbenes results more from stabilizing intramolecular non-covalent interactions in the secondary coordination sphere than from steric hindrance.

Pd/NHC-catalyzed cross-coupling reactions of nitroarenes.

N-Heterocyclic carbene (NHC) ligands effective for the cross-coupling of nitroarenes were identified. A rational design of the NHC ligand structures enabled significant reduction of catalyst loadings compared with the previous system employing BrettPhos as a phosphine ligand. Experimental and theoretical studies to compare these ligands gave some insights into high activity of the newly developed NHC ligands.

Carboallylation of Electron-Deficient Alkenes with Organoboron Compounds and Allylic Carbonates by Cooperative Palladium/Copper Catalysis.

The aryl- and alkylallylation of electron-deficient alkenes was achieved by cooperative palladium/copper catalysis. The reaction affords various carbon skeletons from readily available alkenes, allylic carbonates, and organoboron compounds, whereby a variety of functional groups such as acetyl, alkoxycarbonyl, bromo, and cyano moieties are tolerated well.

Pd-Catalyzed Denitrative Intramolecular C-H Arylation.

A Pd-catalyzed intramolecular C-H arylation of nitroarenes has been developed. Nitroarenes bearing tethered aryl groups at the ortho-position can be readily prepared in one step from 2-halonitroarenes by a nucleophilic aromatic substitution (SNAr). Under Pd/BrettPhos catalysis, activations of the C-NO2 bond as well as the C-H bond on arenes generated the corresponding biaryl linkage in moderate to excellent yields.

Characterization of Rh-Al Bond in Rh(PAlP) (PAlP = Pincer-type Diphosphino-Aluminyl Ligand) in Comparison with Rh(L)(PMe3)2 (L = AlMe2, Al(NMe2)2, BR2, SiR3, CH3, Cl, or OCH3): Theoretical Insight.

The unique Rh-Al bond in recently synthesized Rh(PAlP) 1 {PAlP = pincer-type diphosphino-aluminyl ligand Al[NCH2(P iPr2)]2(C6H4)2NMe} was investigated using the DFT method. Complex 1 has four doubly occupied nonbonding d orbitals on the Rh atom and one Rh d orbital largely participating in the Rh-Al bond which exhibits considerably large bonding overlap between Rh and Al atoms like in a covalent bond. Interestingly, Rhδ--Alδ+ polarization is observed in the bonding MO of 1, which is reverse to Rhδ+-Eδ- (E = coordinating atom) polarization found in a usual coordinate bond. This unusual polarization arises from the presence of the Al valence orbital at significantly higher energy than the Rh valence orbital energy. Characteristic features of 1 are further unveiled by comparing 1 with similar Rh complexes RhL(PMe3)2 (2 for L = AlMe2, 3 for L = Al(NMe2)2, 4 for L = BMe2, 5 for L = SiMe3, 6 for L = SiH3, 7 for L = CH3, 8 for L = OMe, and 9 for L = Cl). As expected, 7, 8, and 9 exhibit usual Rhδ+-Eδ- polarization (E = coordinating atom) in the Rh-E bonding MO. On the other hand, the reverse Rhδ--Eδ+ polarization is observed in the Rh-E bonding MOs of 2-5 like in 1, while the Rh-Si bond is polarized little in 6. These results are clearly understood in terms of the valence orbital energy of the ligand. Because the LUMO of 1 mainly consists of the Rh 4dσ, 5s, and 5p orbitals and the Al 3s and 3p orbitals, both Rh and Al atoms play the role of coordinating site for a substrate bearing a lone pair orbital. For instance, NH3 and pyridine coordinate to both Al and Rh atoms with considerably large binding energy. PAlP exhibits significantly strong trans influence, which is as strong as that of SiMe3 but moderately weaker than that of BMe2. The trans influence of these ligands is mainly determined by the valence orbital energy of the ligand and the covalent bond radius of the coordinating E atom.

meta-Selective C-H Borylation of Benzamides and Pyridines by an Iridium-Lewis Acid Bifunctional Catalyst.

We report herein the iridium-catalyzed meta-selective C-H borylation of benzamides by using a newly designed 2,2'-bipyridine (bpy) ligand bearing an alkylaluminum biphenoxide moiety. We also demonstrate the iridium-catalyzed C3-selective C-H borylation of pyridine with a 1,10-phenanthroline (Phen) ligand bearing an alkylborane moiety. It is proposed that the Lewis acid-base interaction between the Lewis acid moiety and the aminocarbonyl group or the sp2-hybridized nitrogen atom accelerates the reaction and controls the site-selectivity.

Carboallylation of electron-deficient alkenes by palladium/copper catalysis.

A method for the carboallylation of electron-deficient alkenes with tetraorganosilicon reagents and allylic carbonates based on Pd/Cu catalysis has been developed. This method affords a wide range of structurally diverse carbon skeletons from readily available starting materials, and tolerates various functional groups.

Rhodium Complexes Bearing PAlP Pincer Ligands.

We report rhodium complexes bearing PAlP pincer ligands with an X-type aluminyl moiety. IR spectroscopy and single-crystal X-ray diffraction analysis of a carbonyl complex exhibit the considerable σ-donating ability of the aluminyl ligand, whose Lewis acidity is confirmed through coordination of pyridine to the aluminum center. The X-type PAlP-Rh complexes catalyze C2-selective monoalkylation of pyridine with alkenes.

Reductive Denitration of Nitroarenes.

The Pd-catalyzed reductive denitration of nitroarenes has been achieved via a direct cleavage of the C-NO2 bonds. The catalytic conditions reported exhibit a broad substrate scope and good functional-group compatibility. Notably, the use of inexpensive propan-2-ol as a mild reductant suppresses the competitive formation of anilines, which are normally formed by other conventional reductions. Mechanistic studies have revealed that alcohols serve as efficient hydride donors in this reaction, possibly through ß-hydride elimination from palladium alkoxides.