Gallium Hydride-Catalyzed Selective Hydroboration of Unsaturated Organic Substrates.

The first examples of tetrasubstituted conjugated bis-guanidinate (CBG) supported monomeric and thermally stable gallium dihalides [LGaX2], (X=Cl (Ga-Cl), I (Ga-I)) and dihydride (Ga-H) [LGaH2] (where L={(ArHN)(ArN)-C=N-C=(NAr)(NHAr)}; Ar=2,6-Et2-C6H3) compounds are reported. The reaction of in situ generated LLi with 1.0 equiv. GaX3 (X=Cl, I) afforded compounds Ga-Cl and Ga-I. The reaction between Ga-Cl and Li[HBEt3] in benzene yielded the dihydride compound Ga-H. All reported compounds (Ga-Cl, Ga-I, and Ga-H) were characterized by NMR, HRMS, and single-crystal X-ray diffraction studies. Ga-H was probed for the hydroboration of carbodiimides (CDI), isocyanates, and isothiocyanates with HBpin. Compound Ga-H was also found effective for the catalytic hydroboration of imines, nitriles, alkynes, esters, and formates, affording the corresponding products in quantitative yields. Stoichiometric reactions with a CDI were performed to establish the catalytic cycle.

Comparison of Two Zinc Hydride Precatalysts for Selective Dehydrogenative Borylation of Terminal Alkynes: A Detailed Mechanistic Study.

The conjugated bis-guanidinate-stabilized zinc hydride complex (I)-precatalyzed chemoselective dehydroborylation of a wide array of terminal alkynes with excellent yields is reported. Further, precatalyst I is compared with a newly synthesized DiethylNacNac zinc hydride precatalyst (III) for selective dehydroborylation of terminal alkynes, and it is discovered that precatalyst I is more active than III. We have studied intra- and intermolecular chemoselective dehydroborylation of terminal alkynes over other reducible functionalities such as alkene, ester, isocyanide, nitro, and heterocycles. The highly efficient precatalyst I shows a turnover number of 48.5 and turnover frequency of up to 60.5 h-1 in the dehydroborylation of 1-ethynyl-4-fluorobenzene (1i). A plausible mechanism for selective dehydrogenative borylation of alkynes has been proposed based on active catalyst isolation and a series of stoichiometric reactions.

Aluminium-Catalyzed Selective Hydroboration of Esters and Epoxides to Alcohols: C-O Bond Activation.

In this work, the molecular aluminium dihydride complex bearing an N, N'-chelated conjugated bis-guanidinate (CBG) ligand is used as a catalyst for reducing a wide range of aryl and alkyl esters with good tolerance of alkene (C=C), alkyne (C≡C), halides (Cl, Br, I and F), nitrile (C≡N), and nitro (NO2 ) functionalities. Further, we investigated the catalytic application of aluminium dihydride in the C-O bond cleavage of alkyl and aryl epoxides into corresponding branched Markovnikov ring-opening products. In addition, the chemoselective intermolecular reduction of esters over other reducible functional groups, such as amides and alkenes, has been established. Intermediates are isolated and characterized by NMR and HRMS studies, which confirm the probable catalytic cycles for the hydroboration of esters and epoxides.

Intermediates, Isolation and Mechanistic Insights into Zinc Hydride-Catalyzed 1,2-Regioselective Hydrofunctionalization of N-Heteroarenes.

The conjugated bis-guanidinate-supported zinc hydride [{LZnH}2; L = {(ArHN) (ArN)-C═N-C═(NAr) (NHAr); Ar = 2,6-Et2-C6H3}] (I)-catalyzed highly demanding exclusive 1,2-regioselective hydroboration and hydrosilylation of N-heteroarenes is demonstrated with excellent yields. This protocol is compatible with many pyridines and N-heteroarene derivatives, including electron-donating and -withdrawing substituents. Catalytic intermediates, such as [(LZnH) (4-methylpyridine)] IIA, [(L'ZnH) (4-methylpyridine) IIA', where L' = CH{(CMe) (2,6-Et2C6H3N)}2)], LZn(1,2-DhiQ) (isoquinoline) III, [L'Zn(1,2-DhiQ) (isoquinoline)] III', and LZn(1,2-(3-MeDHQ)) (3-methylquinoline) V, were isolated and thoroughly characterized by NMR, HRMS, and IR analyses. Furthermore, X-ray single-crystal diffraction studies confirmed the molecular structures of compounds IIA', III, and III'. The NMR data proved that the intermediate III or III' reacted with HBpin and gave a selective 1,2-addition hydroborated product. Stoichiometric experiments suggest that V and III independently reacted with silane, yielding selective 1,2-addition of mono- and bis-hydrosilylated products, respectively. Based on the isolation of intermediates and a series of stoichiometric experiments, plausible catalytic cycles were established. Furthermore, the intermolecular chemoselective hydroboration reaction over other reducible functionalities was studied.

Zinc Hydride Catalyzed Chemoselective Hydroboration of Isocyanates: Amide Bond Formation and C=O Bond Cleavage.

Herein, a remarkable conjugated bis-guanidinate (CBG) supported zinc hydride, [{LZnH}2 ; L={(ArHN)(ArN)-C=N-C=(NAr)(NHAr); Ar=2,6-Et2 -C6 H3 }] (I) catalyzed partial reduction of heteroallenes via hydroboration is reported. A large number of aryl and alkyl isocyanates, including electron-donating and withdrawing groups, undergo reduction to obtain selectively N-boryl formamide, bis(boryl) hemiaminal and N-boryl methyl amine products. The compound I effectively catalyzes the chemoselective reduction of various isocyanates, in which the construction of the amide bond occurs. Isocyanates undergo a deoxygenation hydroboration reaction, in which the C=O bond cleaves, leading to N-boryl methyl amines. Several functionalities such as nitro, cyano, halide, and alkene groups are well-tolerated. Furthermore, a series of kinetic, control experiments and structurally characterized intermediates suggest that the zinc hydride species are responsible for all reduction steps and breaking the C=O bond.

Aluminum-Catalyzed Selective Hydroboration of Nitriles and Alkynes: A Multifunctional Catalyst.

The reaction of LH [L = {(ArNH)(ArN)-C=N-C=(NAr)(NHAr)}; Ar =2,6-Et2-C6H3] with a commercially available alane amine adduct (H3Al·NMe2Et) in toluene resulted in the formation of a conjugated bis-guanidinate (CBG)-supported aluminum dihydride complex, i.e., LAlH2 (1), in good yield. The new complex has been thoroughly characterized by multinuclear magnetic resonance, IR, mass, and elemental analyses, including single-crystal structural studies. Further, we have demonstrated the aluminum-catalyzed hydroboration of a variety of nitriles and alkynes. Moreover, aluminum-catalyzed hydroboration is expanded to more challenging substrates such as alkene, pyridine, imine, carbodiimide, and isocyanides. More importantly, we have shown that the aluminum dihydride catalyzed both intra- and intermolecular chemoselective hydroboration of nitriles and alkynes over other reducible functionalities for the first time.

Mono- and Bimetallic Aluminum Alkyl, Alkoxide, Halide and Hydride Complexes of a Bulky Conjugated Bis-Guanidinate(CBG) Ligand and Aluminum Alkyls as Precatalysts for Carbonyl Hydroboration.

Tetra-aryl-substituted symmetrical conjugated bis-guanidine (CBG) ligands such as L1-3 (3H) [L(3H) = {(ArHN)(ArHN)C═N-C═NAr(NHAr)}; Ar = 2,6-Me2-C6H3 (L1(3H)), 2,6-Et2-C6H3 (L2(3H)), and 2,6-iPr2-C6H3 (L3(3H))] have been employed to synthesize a series of four- and six-membered aluminum heterocycles (1-8) for the first time. Generally, aluminum complexes bearing N,N'- chelated guanidinate and ß-diketiminate/dipyrromethene ligand systems form four- and six-membered heterocycles, respectively. However, the conjugated bis-guanidine ligand has the capability of forming both four- and six-membered heterocycles possessing multimetal centers within the same molecule; this is due to the presence of three acidic protons, which can be easily deprotonated (at least two protons) upon treatment with metal reagents. Both mono- and dinuclear aluminum alkyls and mononuclear aluminum alkoxide, halide, and hydride complexes have been structurally characterized. Further, we have demonstrated the potential of mononuclear, six-membered CBG aluminum dialkyls in catalytic hydroboration of a broad range of aldehydes and ketones with pinacolborane (HBpin).

Psychosomatic symptoms during South East Asian haze crisis are related to changes in cerebral hemodynamics.

OBJECTIVES: Forest fires in South Asia lead to widespread haze, where many healthy individuals develop psychosomatic symptoms. We investigated the effects of haze exposure on cerebral hemodynamics and new symptoms. We hypothesised that vasoactive substances present in the haze, would lead to vasodilation of cerebral vasculature, thereby altering cerebral hemodynamics, which in turn may account for new psychosomatic symptoms. METHODS: Seventy-four healthy volunteers were recruited, and serial transcranial Doppler (TCD) ultrasonography was performed to record blood flow parameters of bilateral middle cerebral arteries (MCA). The first TCD was performed in an air-conditioned environment. It was repeated outdoors after the participants spent 30-minutes in the haze environment. The prevailing level of pollutant standards index (PSI) was recorded. Appropriate statistical analyses were performed to compare cerebral hemodynamics at baseline and after haze exposure in all participants. Subgroup analyses were then employed to compare the findings between symptomatic and asymptomatic participants. RESULTS: Study participants' median age was 30 years (IQR 26-34), and new psychosomatic symptoms were reported by 35 (47.3%). There was a modest but significant decrease in pulsatility index (PI) and resistivity index (RI) in the left MCA after haze exposure (PI: p = 0.026; RI: p = 0.021). When compared to baseline parameters, haze exposure resulted in significantly lower mean PI (p = 0.001) and RI (p = 0.001) in symptomatic patients, but this difference was not present in asymptomatic patients (PI: p = 0.919; RI: p = 0.970). CONCLUSION: Haze causes significant alterations in cerebral hemodynamics in susceptible individuals, probably responsible for various psychosomatic symptoms. The prognostic implications and health effects of haze require evaluation in a larger study.

Cerebrovascular ultrasonography for selecting patients for stroke intervention.

Currently employed diagnostic ultrasonography provides clinically relevant information about cerebral hemodynamic changes in patients with cerebrovascular ischemia. The information thus obtained is often helpful to the physician for establishing or confirming the diagnosis and prognosis as well as in taking appropriate therapeutic decisions. It is associated with a high temporal resolution and can be performed bedside for rapid diagnosis as well as prolonged monitoring. Transcranial Doppler (TCD) ultrasonography is a non-invasive diagnostic modality that provides physiological information regarding various intracranial hemodynamic alterations in patients with cerebrovascular ischemia. Extended applications of TCD are useful in understanding various pathophysiological mechanisms responsible for the clinical manifestations of cerebrovascular ischemia. Thus, TCD is aptly called as the 'stethoscope' of a stroke neurologist. Cerebrovascular ultrasonography is considered as an essential component of a comprehensive stroke center. We have reviewed various recent patents pertaining to the applications of cerebrovascular ultrasonography employed in the selection of stroke patients for various therapeutic interventions.

Acute ischemic stroke: comparison of low-dose and standard-dose regimes of tissue plasminogen activator.

Intravenous tissue plasminogen activator (IV-TPA), administered within 4.5 h of symptom onset, is the only therapeutic agent approved for achieving arterial recanalization in acute ischemic stroke. Current major guidelines recommend the use of a standard dose (0.9 mg/kg bodyweight; maximum 90 mg) of IV-TPA. However, comparable efficacy of IV-TPA was demonstrated in the observational studies from Japan when a lower dose (0.6 mg/kg bodyweight; maximum 60 mg) was used and later approved by the regulatory authorities. Although limited in numbers, considerable variations in the dose of IV-TPA are noted in recent publications from Asia, with variable results and optimal dose of TPA in Asia remains controversial. The authors present a systemic review of the existing literature and compare the efficacy and safety of standard-versus the low-dose IV-TPA therapy in acute ischemic stroke.