N-Heterocyclic carbene/palladium synergistic catalysis in organic synthesis.

The cooperation of two distinct catalytic cycles to activate different reactive centers leading to a chemical transformation has been classified as synergistic catalysis. The synergistic combination of NHC with palladium catalysis has emerged as a powerful strategy in the last few years. Merging the ability of NHCs to inverse the polarity of a functional group with the unique reactivity of palladium enables transformations that cannot be accomplished by either of these catalysts alone. Despite the associated challenges, such as quenching of catalysts, reactivity mismatch etc., significant development has been achieved in the field of NHC/Pd synergistic catalysis. The recent incorporation of photoredox catalysis with NHC/Pd synergistic catalysis has further advanced this area. This review highlights the developments made in the area of NHC/Pd synergistic catalysis.

Pd/Brønsted acid catalysed intramolecular N-allylation of indoles and pyrroles with alkynes for the synthesis of N-fused heterocycles.

We, herein, report a Pd(0) and Brønsted acid-catalyzed redox-neutral intramolecular N-allylation of indoles and pyrroles with alkynes for the synthesis of biologically important imidazolidinone-fused N-heterocycles. The allylation is completely atom-economical and is applicable to a wide range of substrates. The methodology eliminates the use of a leaving group or an oxidizing agent, often employed for the allylation of nucleophiles. To the best of our knowledge, N-allylation of indoles and pyrroles with alkynes has not been reported to date.

Synthesis of tricyclic oxazinoindolones via Pd-catalyzed intramolecular addition of carboxylic acids to alkynes.

A completely atom-economical synthesis of the oxazinoindolone core via the Pd-catalyzed intramolecular addition of carboxylic acids to alkynes has been developed. Oxazinoindolones have been known to have varied biological activities. The reaction proceeds via 6-exo-dig cyclization and affords the products in high yields (55-93%). The developed method demonstrates the applicability of a Pd(0) complex in combination with a substrate-tethered acid for the 1,2-addition of carboxylic acids to alkynes.

Cognitive effects of unilateral thalamotomy for tremor: a meta-analysis.

Tremor is a debilitating symptom that can lead to functional impairment. Pharmacotherapy is often successful, but up to 50% of patients are resistant to medications or cannot tolerate side effects. Thalamotomy to the ventral intermediate nucleus of the thalamus is a surgical intervention for refractory tremor. Thalamotomy surgeries include radiofrequency and incisionless procedures, such as Gamma Knife radiosurgery and magnetic resonance-guided focused ultrasound. Cognitive changes following thalamotomy have been inconsistently reported across studies. We performed a meta-analysis to summarize the impact of unilateral thalamotomy to the ventral intermediate nucleus of the thalamus across multiple cognitive domains. We searched MEDLINE, Embase Classic, Embase and EBM Reviews for relevant studies. Neuropsychological tests were categorized into seven cognitive domains: global cognition, verbal memory, non-verbal memory, executive function, phonemic fluency, semantic fluency and visuospatial processing. We calculated standardized mean differences as Hedges' g and 95% confidence intervals of the change between pre- and postoperative cognitive scores. Pooling of standardized mean differences across studies was performed using random-effects models. Risk of bias across studies and quality of evidence for each cognitive domain were assessed with the National Institute of Health quality assessment tool and the GRADEpro Guideline Development Tool, respectively. Of the 1251 records reviewed, eight studies met inclusion criteria. We included 193 patients with essential tremor, Parkinson's disease, or multiple sclerosis in the meta-analysis. There was a small significant decline in phonemic fluency [standardized mean difference = -0.29, 95% confidence interval: (-0.52, -0.05), P = 0.017] and a trend towards a decline in semantic fluency [standardized mean difference = -0.19, 95% confidence interval: (-0.40, 0.01), P = 0.056]. No postoperative changes were observed in the other cognitive domains (P values >0.14). In secondary analyses, we restricted the analyses to studies using magnetic resonance-guided focused ultrasound given its growing popularity and more precise targeting. In those analyses, there was no evidence of cognitive decline across any domain (P values >0.37). In terms of risk of bias, five studies were rated as 'good' and three studies were rated as 'fair'. According to GRADEpro guidelines, the certainty of the effect for all cognitive domains was low. This study provides evidence that unilateral thalamotomy to the ventral intermediate nucleus of the thalamus is relatively safe from a cognitive standpoint, however, there may be a small decline in verbal fluency. Magnetic resonance-guided focused ultrasound might have a more favourable postoperative cognitive profile compared with other thalamotomy techniques.

Catalytic enantioselective cross dehydrogenative coupling of sp3 C-H of heterocycles.

C-C bond formation in heterocycles via the direct coupling of C-H bonds, under oxidative conditions, classified as cross dehydrogenative coupling (CDC), is without doubt one of the most atom efficient methods for the functionalization of these molecules. The most common is the coupling at the position alpha to the heteroatom, owing to the stabilization of forming carbocation by the heteroatom. The corresponding asymmetric versions, except for a few isolated reports, have been rather evasive for several years. Optically active heterocycles with the chiral center alpha to the heteroatom are widely present in natural products and pharmaceuticals, thus making them an attractive synthetic target. Persistent efforts towards the asymmetric CDC of heterocycles since the beginning of this decade have led to several developments in this challenging area. Particularly, in the last few years, considerable progress has been witnessed in this field. This review summarizes the progress made in the area of asymmetric cross dehydrogenative coupling of heterocycles in recent years. The review covers the catalytic asymmetric CDC of sp3 C-H bonds of the heterocycles with various coupling partners and illustrates the different catalytic systems employed.

Autoimmune encephalitis: A costly condition.

OBJECTIVE: To assess the inpatient hospitalization burden and costs of patients with autoimmune encephalitis (AE) at a tertiary care institution. METHODS: Adult inpatients with AE were identified retrospectively from July 1, 2005, to June 30, 2015. Demographic and clinical data were collected and analyzed. Billing data were compared to those of patients with herpes simplex encephalitis (HSE). Charges were adjusted for inflation. RESULTS: Of 244 admissions for encephalitis reviewed, 63 patients met criteria for probable or definite AE. Thirty-one (49%) patients were antibody positive, and 27 (43%) were admitted to the intensive care unit (ICU). Median hospital charges per patient with AE were more than $70,000; median length of stay (LOS) was 15 days; and in-hospital mortality was 6%. Patients admitted to the ICU had substantially higher median hospital charges (ICU $173,000 per admission vs non-ICU $50,000 per admission, p < 0.001). LOS was strongly associated with charges and was driven by delay in diagnosis of AE, prolonged treatment courses, and lack of response to therapy. Compared with HSE, median hospital charges per patient with AE were nearly 4 times higher, median AE LOS was 3 times higher, and total charges over the study period were nearly twice as high. CONCLUSIONS: Patients with AE used more inpatient health care resources per patient during a 10-year period than patients with HSE at our institution. ICU-admitted patients with AE were responsible for a substantially higher financial burden than non-ICU-admitted patients with AE. Our data underscore the need for the development of novel diagnostic and therapeutic modalities to improve patient outcomes and to decrease hospital burden in AE.

Catalytic asymmetric three-component synthesis of homoallylic amines.

It takes three to make things go right: The first direct asymmetric three-component reaction of aldehydes, carbamates, and allyltrimethylsilane leading to enantioenriched homoallylic amines has been developed using a new chiral disulfonimide catalyst. The method employs readily available, inexpensive, and nontoxic starting materials and is applicable to both aromatic and aliphatic aldehydes.

Supplemental maxillomandibular fixation with miniplate osteosynthesis-required or not?

AIM: To compare outcomes of open reduction and internal fixation of mandible fractures followed by either immediate mobilization or 5 days of maxillomandibular fixation. MATERIAL AND METHODS: We analyzed our use of supplemental maxillomandibular fixation with miniplate osteosynthesis during a 2.5-year period in 118 patients with 180 mandible fractures. A retrospective, matched pairing of identical fractures fixated with identical plating schemes was carried out. Thirty-five pairs of patients undergoing monocortical plating were identified. Patients in group 1 were treated with supplemental maxillomandibular fixation after surgery, whereas patients in group 2 (immediate release group) were treated without postoperative maxillomandibular fixation. RESULTS: The total rate of complications was 17% with supplemental maxillomandibular fixation and 14% without supplemental maxillomandibular fixation (p > 0.05). No statistically significant outcome advantage could be attributed to the use of maxillomandibular fixation. CONCLUSION: The current retrospective study shows no significant differences in treating isolated mandible fractures with open reduction and internal fixation and immediate release versus open reduction and internal fixation with 5-7 days of MMF.

Synthesis of chiral organocatalysts derived from aziridines: application in asymmetric aldol reaction.

We report the synthesis of a new series of highly efficient chiral organocatalysts derived via the regio- and stereoselective ring opening of chiral aziridines with azide anions. The catalysts have proved to be very efficient for a direct asymmetric aldol reaction, both with cyclic as well as acyclic ketones in brine with 2 mol % of catalyst loading, and afforded the products in excellent yields (up to 99%) and enantioselectivities (up to >99%). The chiral aldol adduct obtained has further been converted to a chiral azetidine ring via a convenient pathway.

Studies on the reaction of aziridines with nitriles and carbonyls: synthesis of imidazolines and oxazolidines.

Reaction of N-tosylaziridines with nitriles and carbonyls to produce imidazolines and oxazolidines has been studied in the presence of a variety of Lewis acids. The reaction is efficient with 1 equiv of BF3.Et2O or Et3OBF4 in CH2Cl2. However, it is catalytic with metal triflates that give the best results for cycloaddition of N-tosylaziridine with nitriles under solvent free conditions. The same reaction with carbonyls proceeds best in CH2Cl2 in the presence of molecular sieves. Among various triflates, Zn(OTf)2 has been found to be the best. The cleavage of the N-Ts bond of the cyclized products has been studied in order to make it more versatile in synthesis. The mechanistic aspect of the reaction has been studied by using chiral aziridines as substrates. These formal [3+2] cycloaddition reactions of aziridines with nitriles and carbonyls proceed in a Ritter fashion.