Imaging follow-up strategy after endovascular treatment of Intracranial aneurysms: A literature review and guideline recommendations.

OBJECTIVE: Endovascular coil embolization is the primary treatment modality for intracranial aneurysms. However, its long-term durability remains of concern, with a considerable proportion of cases requiring aneurysm reopening and retreatment. Therefore, establishing optimal follow-up imaging protocols is necessary to ensure a durable occlusion. This study aimed to develop guidelines for follow-up imaging strategies after endovascular treatment of intracranial aneurysms. METHODS: A committee comprising members of the Korean Neuroendovascular Society and other relevant societies was formed. A literature review and analyses of the major published guidelines were conducted to gather evidence. A panel of 40 experts convened to achieve a consensus on the recommendations using the modified Delphi method. RESULTS: The panel members reached the following consensus: 1. Schedule the initial follow-up imaging within 3-6 months of treatment. 2. Noninvasive imaging modalities, such as three-dimensional time-of-flight magnetic resonance angiography (MRA) or contrast-enhanced MRA, are alternatives to digital subtraction angiography (DSA) during the first follow-up. 3. Schedule mid-term follow-up imaging at 1, 2, 4, and 6 years after the initial treatment. 4. If noninvasive imaging reveals unstable changes in the treated aneurysms, DSA should be considered. 5. Consider late-term follow-up imaging every 3-5 years for lifelong monitoring of patients with unstable changes or at high risk of recurrence. CONCLUSIONS: The guidelines aim to provide physicians with the information to make informed decisions and provide patients with high-quality care. However, owing to a lack of specific recommendations and scientific data, these guidelines are based on expert consensus and should be considered in conjunction with individual patient characteristics and circumstances.

Feasibility of Prompt Lumbar Drainage in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Numerous studies have shown that continuous lumbar drainage (LD) reduces spontaneous subarachnoid hemorrhage (SAH)-related complications, decreasing the incidence of cerebral vasospasm, delayed cerebral ischemia , and hydrocephalus in patients treated with coiling or clipping, but performing LD before securing the aneurysm is still controversial. Our hospital has been implementing prompt LD for several years, and we present the results in this paper. METHODS: Between January 2014 and December 2020, a total of 438 patients with SAH were included in this retrospective study. The indication for prompt LD was aneurysmal SAH of modified Fisher grade III or higher without dense intraventricular hemorrhage with obstructive hydrocephalus requiring extraventricular drainage or large intracranial hemorrhage requiring immediate decompression. Prompt LD was performed for 229 patients with SAH, and the control group included 209 patients. We compared in-hospital mortality and vasospasm or hydrocephalus occurrence and procedure-related complications between the two groups. RESULTS: The in-hospital mortality rate was 7.4% for patients with prompt LD and 14.4% for patients without LD, and the difference was significant (P = 0.019). Vasospasm occurred in 10% of patients with prompt LD and 16.7% of controls (P = 0.039). Hydrocephalus requiring extraventricular drainage occurred in 10.9% of the LD group and 28.7% of the control group (P < 0.001). Rebleeding occurrence was 3.1% in the prompt LD group and 5.7% in the non-LD group (P = 0.168). Cerebrospinal fluid infection occurred in 0.4% of the prompt LD group and 1.4% of controls(P = 0.272). CONCLUSIONS: Prompt LD is a feasible option for treating patients with selective aneurysmal SAH.

Preliminary Study on Natural Killer Cell Activity for Interferon-Gamma Production after Gamma Knife Radiosurgery for Brain Tumors.

OBJECTIVE: High-dose radiation is well known to induce and modulate the immune system. This study was performed to evaluate the correlation between clinical outcomes and changes in natural killer cell activity (NKA) after Gamma Knife Radiosurgery (GKS) in patients with brain cancer. METHODS: We performed an open-label, prospective, cross-sectional study of 38 patients who were treated with GKS for brain tumors, including metastatic and benign brain tumors. All of the patients underwent GKS, and blood samples were collected before and after GKS. NKA was measured using an enzyme-linked immunosorbent assay kit, to measure interferon-gamma (IFNγ) secreted by ex vivo-stimulated NK cells from whole blood. We explored the correlations between NK cell-produced IFNγ (NKA-IFNγ) levels and clinical parameters of patients who were treated with GKS for brain tumors. RESULTS: NKA-IFNγ levels were decreased in metastatic brain tumor patients compared to those with benign brain tumors (p<0.0001). All the patients who used steroid treatment to reduce brain swelling after GKS had an NKA-IFNγ level of zero except one patient. High NKA-IFNγ levels were not associated with a rapid decrease in brain metastasis and did not increase after GKS. CONCLUSION: The activity of NK cells in metastatic brain tumors decreased more than that in benign brain tumors after GKS.

Outcomes of Mechanical Thrombectomy in Patients with Large Diffusion-Weighted Imaging Lesions.

OBJECTIVE: Despite many advancements in endovascular treatment, the benefits of mechanical thrombectomy (MT) in patients with large infarctions remain uncertain due to hemorrhagic complications. Therefore, we aimed to investigate the efficacy and safety of recanalization via MT within 6 hours after stroke in patients with large cerebral infarction volumes (>70 mL). METHODS: We retrospectively reviewed the medical data of 30 patients with large lesions on initial diffusion-weighted imaging (>70 mL) who underwent MT at our institution within 6 hours after stroke onset. Baseline data, recanalization rate, and 3-month clinical outcomes were analyzed. Successful recanalization was defined as a modified treatment in cerebral ischemia score of 2b or 3. RESULTS: The recanalization rate was 63.3%, and symptomatic intracerebral hemorrhage occurred in six patients (20%). The proportion of patients with modified Rankin Scale (mRS) scores of 0-3 was significantly higher in the recanalization group than in the non-recanalization group (47.4% vs. 9.1%, p=0.049). The mortality rate was higher in the non-recanalization group, this difference was not significant (15.8% vs. 36.4%, p=0.372). In the analysis of 3-month clinical outcomes, only successful recanalization was significantly associated with mRS scores of 0-3 (90% vs. 50%, p=0.049). The odds ratio of recanalization for favorable outcomes (mRS 0-3) was 9.00 (95% confidence interval, 0.95-84.90; p=0.055). CONCLUSION: Despite the risk of symptomatic intracerebral hemorrhage, successful recanalization via MT 6 hours after stroke may improve clinical outcomes in patients with large vessel occlusion.

Mechanical thrombectomy for acute ischemic stroke with occlusion of the M2 segment of the middle cerebral artery: A literature review.

Thanks to new generation devices, mechanical thrombectomy (MT) has substantially evolved and become the standard treatment for patients with acute occlusion of the internal carotid artery or proximal middle cerebral artery (MCA) (M1 segment). However, the role and benefit of MT in patients with distal MCA (M2 segment) occlusion remain unclear. Therefore, there is a need for further studies. To evaluate the efficacy and safety of MT for M2 occlusion, this article reviews the natural course of M2 occlusion, the evidence regarding MT for M2 segment occlusion, clinical outcomes of MT for M2 occlusion, and treatment outcomes according to device type.

Modified Suturing Techniques in Carotid Endarterectomy for Reducing the Cerebral Ischemic Time.

OBJECTIVE: Carotid endarterectomy (CEA) is an effective surgical procedure for treating symptomatic or asymptomatic patients with carotid stenosis. Many neurosurgeons use a shunt to reduce perioperative ischemic complications. However, the use of shunting is still controversial, and the shunt procedure can cause several complications. In our institution, we used two types of modified arteriotomy suture techniques instead of using a shunt. METHODS: In technique 1, to prevent ischemic complications, we sutured a third of the arteriotomy site from both ends after removing the plaque. Afterward, the unsutured middle third was isolated from the arterial lumen by placing a curved Satinsky clamp. And then, we opened all the clamped carotid arteries before finishing the suture. In technique 2, we sutured the arteriotomy site at the common carotid artery (CCA). We then placed a curved Satinsky clamp crossing from the sutured site to the carotid bifurcation, isolating the unsutured site at the internal carotid artery (ICA). After placing the Satinsky clamp, the CCA and external carotid artery (ECA) were opened to allow blood flow from CCA to ECA. By opening the ECA, ECA collateral flow via ECA-ICA anastomoses could help to reduce cerebral ischemia. RESULTS: The modified suture methods can reduce the cerebral ischemia directly (technique 1) or via using collaterals (technique 2). The modified arteriotomy suture techniques are simple, safe, and applicable to almost all cases of CEA. CONCLUSION: Two modified arteriotomy suture techniques could reduce perioperative ischemic complications by reducing the cerebral ischemic time.

Clinical warning signs of life-threatening hematochezia in neurosurgical patients with long-term bed rest: Three cases report.

RATIONALE: Patients with long term bed rest in intensive care unit after neurosurgery could experience splanchnic hypoperfusion. These patients have several other medical conditions that exacerbate splanchnic hypoperfusion during treatment and the splanchnic hypoperfusion could result in "stress-induced intestinal necrosis", which could cause massive hematochezia. We report here the experience of life-threatening hematochezia in 3 patients who underwent brain surgery in our institution. PATIENTS CONCERNS: One female patient (72-year-old) and 2 male patients (58- and 35-year-old) were admitted to our institution because of traumatic intracerebral hemorrhage, subarachnoid hemorrhage due to a ruptured anterior communicating artery, and subarachnoid hemorrhage with unknown cause respectively. All patients underwent emergency brain surgery for diagnosis and treatment. After surgery, they all experienced long-term bed rest in intensive care unit. Hematochezia occurred on postoperative day 15, 17, and 49, respectively. DIAGNOSES: All of the patients were assessed by abdomen/pelvis computed tomography and underwent a colonoscopy. INTERVENTIONS: The female patient underwent embolization through pelvic arteriography and epinephrine injection through colonoscopy, but a total colectomy and ileostomy was performed due to refractory hematochezia. 58-year-old male patient had a laparoscopic ileostomy for the bowel rest. The other patient underwent nil per os and conservative treatment for 2 weeks. OUTCOMES: The female patient was discharged without further treatment plan, 58-year-old male patient survived after laparoscopic ileostomy, while the other patient survived after 2 weeks of nil per os. LESSON: Abdominal symptoms, such as hematochezia, should be actively managed in neurosurgical patients who are undergoing long-term bed rest in an intensive care unit under physiologically stressful medical conditions.

Wedge Resection of the Falx to Clip a Distal Anterior Cerebral Artery Aneurysm.

BACKGROUND: The unilateral anterior interhemispheric approach has been widely used for distal anterior cerebral artery (DACA) aneurysms. However, there are some drawbacks of this approach because of the narrow operative field, including possible brain traction injury, bridging vein injury, and inadequate exposure of the aneurysm. Here, we report a case of a DACA aneurysm covered by the falx that could not be totally exposed with the unilateral interhemispheric approach. We successfully obtained a wide view with wedge resection of the falx, avoiding excessive brain traction and division of the superior sagittal sinus. CASE DESCRIPTION: A 76-year-old woman with a 6-mm unruptured DACA aneurysm underwent a unilateral craniotomy with the anterior interhemispheric approach. In the operative field, the aneurysm was found at the midline, just below the falx. The aneurysm was covered by the falx and could not be completely exposed with the usual brain retraction. Therefore, we performed wedge resection of the falx, thus obtaining sufficient surgical field and totally exposing the aneurysm. We were then able to apply the clip successfully. Postoperative brain computed tomography angiography showed no remnant aneurysm sac or complications of falx resection or brain retraction, such as bleeding or vessel injury. CONCLUSIONS: When an aneurysm is located just below the falx and is exposed inadequately, performing wedge resection of the falx can expose the aneurysms adequately for application of the clip.

Vasa Vasorum Densities in Human Carotid Atherosclerosis Is Associated with Plaque Development and Vulnerability.

OBJECTIVE: The extensive vasa vasorum network functions as a conduit for the entry of inflammatory cells or factors that promote the progression of angiogenesis and plaque formation. Therefore, we investigated the correlation between the carotid vasa vasorum activities and carotid plaque vulnerability using indocyanine green video angiography (ICG-VA) during carotid endarterectomy (CEA). METHODS: Sixty-nine patients who underwent CEA were enrolled prospectively from September 2015 to December 2017. During CEA, a bolus of ICG was injected intravenously before and after resecting the atheroma. Additionally, we performed immunohistochemistry using CD68 (a surface marker of macrophages), CD117 (a surface marker of mast cells), and CD4 and CD8 (surface markers of T-cells) antibodies to analyze the resected plaque specimens. RESULTS: The density of active vasa vasorum was observed in all patients using ICG-VA. The vasa vasorum externa (VVE) and interna (VVI) were seen in 11 (16%) and 57 patients (82.6%), respectively. Macroscopically, the VVE-type patterns were strongly associated with preoperative angiographic instability (81.8%, p=0.005) and carotid plaque vulnerability (90.9%, p=0.017). In contrast, the VVI-type patterns were weakly associated with angiographic instability (31.6%) and plaque vulnerability (49.1%). CD68-stained macrophages and CD117-stained mast cells were observed more frequently in unstable plaques than in stable plaques (p<0.0001, p=0.002, respectively). CONCLUSION: The early appearance of VVE, along with the presence of many microvessel channels that provided nutrients to the developing and expanding atheroma during ICG-VA, was strongly associated with unstable carotid plaques. The degree of infiltration of macrophages and mast cells is possibly related to the formation of unstable plaques.

Paintable and writable electrodes using black conductive ink on traditional Korean paper (Hanji).

We demonstrate black conductive ink (BCI) that is writable and paintable on traditional handmade Korean paper (Hanji) for application as a high performing electrode. By optimal mixing of Ag nanowire (Ag NW) suspension and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)(PEDOT:PSS) solution in standard charcoal-based blank ink, we synthesized BCI suitable for writing and painting on Hanji with a normal paintbrush. Due to the shear stress induced by the paintbrush bristles, the Ag NW and PEDOT:PSS mixture was uniformly coated on the porous cellulose structure of Hanji and showed a low sheet resistance of 11.7 Ohm per square even after repeated brush strokes. Moreover, the brush-painted electrodes on Hanji showed a constant resistance during tests of inner/outer bending and folding due to the outstanding flexibility of the Ag NW and PEDOT:PSS mixture that filled the porous cellulose structure of Hanji. Therefore, the pictures drawn in the BCI on Hanji exhibited a level of flexibility and conductivity sufficiently high to enable the BCI to function as an effective electrode even when the paper substrate is wrinkled or crumpled. The successful operation of the paintable interconnector and heater on Hanji indicates the high potential of the brush-painted electrodes that can be used in various social and cultural fields, including fine art, fashion, interior design, architecture, and heating industry.

Contralateral Brain Atrophy in Conservatively Treated Primary Intracerebral Hemorrhage.

BACKGROUND: In patients with intracerebral hemorrhage (ICH), brain volume loss can occur in the hemisphere ipsilateral to the hematoma. However, contralateral hemispheric volume change after ICH is not well known. The present study aimed to investigate contralateral brain volume changes in patients with ICH who had not undergone surgery. METHODS: Of the 2213 patients with ICH admitted to our hospital between January 2010 and December 2017, 46 patients without surgical intervention were included in the present study. We measured contralateral hemispheric brain volume in the axial images of brain computed tomography at the time of ICH onset and after 12 months. We analyzed the relationship between various factors and volume changes in the contralateral hemisphere. RESULTS: The mean change percentage between the initial and follow-up contralateral parenchyma volume was 96.84%. The average volume decreased by 3.16% (P = 0.001). Univariate and multivariate logistic regression models revealed no significant factors associated with contralateral brain volume loss. Kruskal-Wallis test and Mann-Whitney U test showed no statistical significance (P = 0.824, P = 0.122) between ICH volume groups. CONCLUSIONS: Contralateral parenchymal volumes were significantly decreased at follow-up brain computed tomography scanning; these changes may provide important clinical information on the remote effect of focal lesion and symptoms in the course of ICH treatment. However, further investigation is required to determine the mechanisms underlying these volume changes.

Preoperative Considerations in Occipital Artery-high-riding Posterior Inferior Cerebellar Artery Bypass: A Report of Two Cases and a Literature Review.

Nonsaccular vertebral artery aneurysms involving the posterior inferior cerebellar artery (PICA) are rare. Treatment is considered a significant challenge because of their angiographic and anatomical features, especially in high-riding PICA. Therefore, meticulous preoperative angiographic and anatomical evaluation is necessary. Moreover, consideration of the distance between the cerebellar skull base and caudal loop of the PICA is important. We present two cases of occipital artery-high-riding PICA bypass and discuss important preoperative technical considerations.

Bifrontal Interhemispheric Approach Involving Cutting the Superior Sagittal Sinus for Distal Anterior Cerebral Artery Aneurysms.

BACKGROUND: The unilateral interhemispheric approach for distal anterior cerebral artery aneurysms presents several risks, such as postoperative venous infarction due to occasional sacrifice of parasagittal bridging vein and postoperative frontal lobe damage due to retraction force. To overcome these risks, we used a bifrontal craniotomy with straight dural incision and cutting of the superior sagittal sinus. METHODS: We retrospectively reviewed 61 patients (42 unruptured and 19 ruptured A2 and A3 aneurysms) who under aneurysm clipping through bifrontal interhemispheric approach between March 2007 and December 2017. There were 35 A2 aneurysms and 27 A3 aneurysms, and mean size of aneurysms was 5.45 mm. The modified bifrontal interhemispheric approach involved 3 steps: bifrontal craniotomy of centrobasal portion of the frontal bone, ligation and division of anterior one third of the superior sagittal sinus, and approaching the aneurysm via the interhemispheric space. All patients underwent computed tomography on postoperative days 3 and 7 for evaluation of brain retraction damage or venous infarction. RESULTS: Among patients with ruptured aneurysms, 79% had a favorable outcome (Glasgow Outcome Scale score 4 or 5) 6 months after primary subarachnoid hemorrhage; all patients with unruptured aneurysms had favorable outcomes. Surgical outcome was strongly related to preoperative neurologic Hunt and Hess grade. Three patients had poor outcomes due to poor Hunt and Hess grade on admission (grade 3 in 2 patients, grade 4 in 1 patient). Follow-up CT showed that venous infarction did not occur in any of the patients. CONCLUSIONS: Modified bifrontal interhemispheric approach may be a safe and effective method for treating A2 and A3 aneurysms with relatively good clinical outcome and no surgery-related complications.

High-performance thin H:SiON OLED encapsulation layer deposited by PECVD at low temperature.

Highly moisture permeation resistive and transparent single layer thin films for the encapsulation of hydrogenated silicon oxynitrides (H:SiON) were deposited by plasma-enhanced chemical vapor deposition (PECVD) using silane (SiH4), nitrous oxide (N2O), ammonia (NH3), and hydrogen (H2) at 100 °C for applications to a top-emission organic light-emitting diode (TEOLED). Addition of H2 into the PECVD process of SiON film deposition afforded the hydrogenated SiON film, which showed not only improved optical properties such as transmittance and reflectance but also better barrier property to water permeation than PECVD SiON and even SiN x . The H:SiON film with thickness of only 80 nm exhibited water vapor transmission rate (WVTR) lower than 5 × 10-5 g per m2 per day in the test conditions of 38 °C and 100% humidity, where this WVTR is the measurement limit of the MOCON equipment. An additional coating of UV curable polymer enabled the H:SiON films to be flexible and to have very stable barrier property lower than 5 × 10-5 g per m2 per day even after a number of 10k times bending tests at a curvature radius of 1R. The mild H:SiON film process improved the electrical properties of top-emission OLEDs without generating any dark spots. Furthermore, single H:SiON films having high water vapor barrier could maintain the original illumination features of TEOLED longer than 720 hours. These excellent properties of the H:SiON thin films originated from the structural changes of the SiON material by the introduction of hydrogen.

Diagnostic Value of Thrombus Size on T2(*)-weighted Gradient Echo Imaging in Acute Middle Cerebral Artery Occlusion.

OBJECTIVE: The T2(*)-weighted gradient echo image susceptibility vessel sign (GRE SVS) is a well-known indicator of intraluminal thrombi in acute cerebral infarction. The purpose of this study was to evaluate the relationships between thrombus size on GRE SVS and recanalization after intravenous administration of tissue plasminogen activator (IV-tPA). MATERIALS AND METHODS: Fifty five patients with GRE SVSs on the M1 were enrolled. Examination of magnetic resonance image (MRI), including diffusion weighted imaging and MR angiography, was performed within 20 minutes of admission. Thrombus size on GRE was calculated using the Picture Archiving and Communication System upon initial MRI. Recanalization was assessed with follow-up MRI or transfemoral cerebral angiography within 24 hours of treatment. RESULTS: The patient group consisted of 37 males and 18 females with an average age of 63.74 ± 10.28 years (range: 43 - 77 years). The median NIHSS score was 13. Fifteen of these patients achieved recanalization (27.3%). The average thrombus cross-sectional area in the recanalization group was 38.54 ± 20.27 mm(2), and the corresponding size of the non-recanalization group was 53.38 ± 24.77 mm(2) (p = 0.043). In the receiver operator characteristic curve for thrombus cross-sectional area in relation to recanalization, the cut-off point was 47.28 mm(2). The sensitivity at this cut-off point was 73.3%, the specificity was 60%, and the area under the curve was 0.687. CONCLUSION: Thrombus size on GRE is a simple diagnostic tool that can be easily measured, and thrombus size on GRE SVS was found to be associated with recanalization after IV-tPA.

Oculomotor nerve schwannoma: a case report.

Schwannomas account for about 8% of intracranial tumors and 90% are vestibular schwannomas. Oculomotor schwannoma without neurofibromatosis is extremely rare. A 41-year-old female presented with complaints of blurred vision, and the neurologic examination revealed afferent pupillary defect and decreased visual acuity of the left side. Brain magnetic resonance image showed an extra axial mass in the left superior orbital fissure. The patient underwent major surgery via the fronto-temporal approach. The tumor originated from the oculomotor nerve and was subtotally removed under microscopic surgery. The pathological findings confirmed the tumor as a schwannoma. After surgery, ptosis and medial gaze limitation of the left eye was detected, but the symptoms improved gradually.

Heterotopic Ossification after Cervical Arthroplasty with ProDisc-C: Time Course Radiographic Follow-up over 3 years.

OBJECTIVE: Heterotopic ossification (HO) is a well-known complication after total hip replacement. But the occurrence rate by the time-course, clinical effect and risk factors of HO after total cervical disc replacement (TCDR) are not well described. The purpose of this study is to evaluate the occurrence rate by the time-course and risk factors for HO after TCDR with a ProDisc-C. METHODS: Thirty-two patients whom followed up more than one year after the TCDR are enrolled. Radiographic study was done at 12, 24 and 36 months after the TCDR and classified HO with McAfee classification. Segmental range of motion, preoperative existence of spondylosis, type of operation, disc space occupying ratio by artificial disc, surgical level are analyzed to identify the risk factors of HO. The visual analog scale and the neck disability index were evaluated preoperatively and at last follow-up time for clinical parameters. RESULTS: Eighteen patients (56%) showed HO at 12 months, 18 patients (86%) showed HO at 24 months and 6 patients (89%) showed HO at 36 months after the TCDR. Clinical significant HO(Grade 3 and 4) was shown in one patient (3%) at 12 months, 3 patients (14%) at 24 months and 5 patients (56%) at 36 months. Only post-operative follow-up period increases the risk of development clinical significant HO. All patients showed improvement of clinical parameters (p<0.005). CONCLUSION: Incidence of HO is getting higher as time course progress. However, there are no relation between clinical outcome and radiologic change of ROM and the grade of HO.

Fast triggers for a proton injector at PEFP.

A fast timing system has been developed to control transistor transistor logic (TTL) trigger signals which are used to extract the pulsed proton beam from an ion source with the precision of less than submicro seconds. The system has been designed to set a delay and duty of the pulses, respectively, and prohibit the beam pulse by an external interlock signal. The system is based on VME which is composed of VME CPU and fast I/O boards with fan-out modules. The software of the system has been developed by the record/device supports and channel access in the core of the EPICS environments. In the paper, we describe software configurations and hardware drivers.

Rhodium-catalyzed ring-opening reactions of N-boc-azabenzonorbornadienes with amine nucleophiles.

In the presence of a rhodium catalyst (5 mol %) generated in situ from [Rh(cod)Cl](2) and (S,S')-(R,R')-C(2)-ferriphos (4a), the asymmetric ring-opening reaction of azabenzonorbornadienes (1a-m) with various aliphatic and aromatic amines (2a-l) proceeded with high enantioselectivity (up to >99% ee) to give the corresponding 1,2-diamine derivatives 3 in high yields. In the specific case of pyrrolidine as nucleophile, Et(3)NHCl was necessary as an additive for good reactivity and enantioselectivity. Additionally, a practical protocol was developed for the ring-opening of 1a with volatile amines at elevated temperatures and standard pressure, using R(2)NH(2)I and i-Pr(2)NEt. The experimental results showed that the nature of the chiral ligand has the significant impact on the reactivity of the catalyst and the use of excess amount (2.2 eq to Rh) of the chiral ligand plays an important role to improve the enantioselectivity in the present asymmetric reaction.

Asymmetric synthesis of axially chiral biaryls by nickel-catalyzed grignard cross-coupling of dibenzothiophenes.

Catalytic asymmetric Grignard cross-coupling of 1,9-disubstituted dibenzothiophenes (6a-c) and dinaphthothiophene (6d) with aryl- and alkyl-Grignard reagents (7) proceeded with high enantioselectivity (up to 95% ee) in the presence of a nickel catalyst (3-6 mol %) coordinated with 2-diphenylphosphino-1,1'-binaphthyl (H-MOP) or oxazoline-phosphine ligand (i-Pr-phox) in THF to give 2-mercapto-2'-substituted-1,1'-biphenyls (8a-c) and 2-mercapto-2'-substituted-1,1'-binaphthyls (8d) in high yields. The mercapto group in the axially chiral cross-coupling products was converted into several functional groups by way of the methylsulfinyl group. The rate of flipping in dinaphthothiophene was measured by variable-temperature (31)P NMR analysis of methylphenylphosphinyldinaphthothiophene derivative (21).