Synthesis of Pyrrole via Formal Cycloaddition of Allyl Ketone and Amine under Metal-Free Conditions.

A new metal-free synthesis of pyrrole from allyl ketone and amine has been established. The reaction proceeds via an thiolative activation of the C-C double bond with dimethyl(methylthio)sulfonium trifluoromethanesulfonate, followed by a nucleophilic ring-opening addition of primary amine to the generated episulfonium intermediate, and then an internal condensation and aromatization. This mild procedure provides a novel strategy to the construction of substituted pyrroles through a formal [4 + 1] cycloaddition reaction.

Iron-catalyzed domino decarboxylation-oxidation of α,ß-unsaturated carboxylic acids enabled aldehyde C-H methylation.

A practical and general iron-catalyzed domino decarboxylation-oxidation of α,ß-unsaturated carboxylic acids enabling aldehyde C-H methylation for the synthesis of methyl ketones has been developed. This mild, operationally simple method uses ambient air as the sole oxidant and tolerates sensitive functional groups for the late-stage functionalization of complex natural-product-derived and polyfunctionalized molecules.

Iron-mediated deuterium addition cascade cyano insertion/cyclization of N-arylacrylamides to access deuterium-labelled phenanthridines.

Deuterated molecules feature important biological activities and pharmacokinetic properties for the design of pharmaceuticals. Radical cyclization cascades involving the deuteration of alkenes to form heterocyclic compounds have rarely been reported. Herein, a deuterium addition cascade cyano insertion/cyclization of N-arylacrylamides to synthesize deuterated phenanthridines is described. Cheap Fe(NO3)3·9H2O enables the generation of a deuterium radical from NaBD4in situ. These reactions proceed under mild conditions in a short time and a variety of functional groups are well tolerated.

Bio-inspired iron-catalyzed oxidation of alkylarenes enables late-stage oxidation of complex methylarenes to arylaldehydes.

It is a long-standing challenge to achieve efficient and highly selective aerobic oxidation of methylarenes to benzaldehydes, owing to overoxidation problem stemming from the oxidizability of benzaldehyde far higher than the toluene under usual aerobic conditions. Herein we report a bio-inspired iron-catalyzed polymethylhydrosiloxane-promoted aerobic oxidation of methylarenes to benzaldehydes with high yields and selectivities. Notably, this method can tolerate oxidation-labile and reactive boronic acid group, which is normally required to be transformed immediately after its introduction, and represents a significant advance in the area of the chemistry of organoboronic acids, including the ability to incorporate both aldehyde and ketone functionalities into unprotected arylboronic acids, a class that can be difficult to access by current means. The robustness of this protocol is demonstrated on the late-stage oxidation of complex bioactive molecules, including dehydroabietic acid, Gemfibrozil, Tocopherol nicotinate, a complex polyol structure, and structurally complex arylboronic acids.

Iron-catalyzed oxidative C-C(vinyl) σ-bond cleavage of allylarenes to aryl aldehydes at room temperature with ambient air.

A general and selective iron-catalyzed allylic C-C(vinyl) σ-bond cleavage of allylarenes without the assistance of heteroatoms to give aryl aldehydes is reported. The unstrained carbon-carbon single bond cleavage reaction uses ambient air as the sole oxidant, proceeds efficiently at room temperature, and allows for exceptional functional-group tolerance, which addresses the long-standing challenges of current C-C bond cleavage/functionalization. Notably, the method enables rapid late-stage oxidation of complex bioactive molecules and can be used to expedite syntheses of natural products (vanillin and glucovanillin) from readily available chemical feedstocks.

Visible light-induced C3-sulfonamidation of imidazopyridines with sulfamides.

A visible light-induced regioselective sulfonamidation of imidazo[1,2-a]pyridines was developed using sulfamides as the nitrogen sources and aqueous NaClO solution as the oxidant under mild conditions. With the imidazo[1,2-a]pyridines bearing various substituents, the reaction proceeded smoothly to furnish the C3-sulfonamidation products in moderate to good yields. The method was also suitable for the sulfonamidation of some other imidazoheterocycles.

Midterm outcomes of intracranial aneurysms with bleb formation with densely coiling of the aneurismal neck or entire aneurysm.

To evaluate whether the efficacy and safety of embolization of the aneurysmal neck were better than those of embolization of the entire aneurysm. Previous studies found that embolization of the aneurysmal neck can be used for treating ruptured intracranial aneurysm with bleb formation.In all, 163 patients with ruptured aneurysms with bleb formation who underwent endovascular embolization at the Shanghai Municipal Jing'an District Central Hospital from January 2014 to August 2015 were divided into the embolization of aneurysmal neck group (neck group; 87 cases) and embolization of entire aneurysm group (aneurysm group; 76 cases). A retrospective analysis of clinical data, follow-up Glasgow Outcome Scale (GOS) score, and occurrence of complications was performed. The impacts of different embolisms on the prognosis were compared.The median follow-up time in the neck and aneurysm groups was 17 months (9.62) and 16.5 months (9.54), respectively (P = .799). No differences were found in recurrence, postoperative GOS score, and GOS score at the last follow-up between the 2 groups. The numbers of coils and surgical complications in the neck group were smaller than those in the aneurysm group (P < .001 and P < .030, respectively). After adjusting for age and sex, the embolization method was found to be an independent predictor for surgery-related complications (odds ratio 2.419, 95% confidence interval 1.111-5.269, P = .026).The numbers of coils and surgery-related complications were smaller when embolizing the aneurysmal neck than the entire aneurysm, showing potential advantages of embolization of the aneurysmal neck.

A novel pyrazole-containing indolizine derivative suppresses NF-κB activation and protects against TNBS-induced colitis via a PPAR-γ-dependent pathway.

The nuclear factor-κB (NF-κB)-mediated activation of macrophages plays a key role in mucosal immune responses in Crohn's disease (CD). Moreover, increasing evidence shows that the activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) exerts satisfactory anti-inflammatory effects in experimental colitis models, mostly by suppressing NF-κB-mediated macrophage activation. Therefore, exploring therapeutic strategies to activate PPAR-γ and inhibit the NF-κB pathway in colonic macrophages holds great promise for the treatment of CD. In this study, five novel pyrazole-containing indolizine derivatives (B1, B2, B3, B4 and B5) were successfully synthesized and characterized, and their anti-inflammatory activities for CD treatment were also investigated. Among the five compounds, compound B4 effectively decreased the NF-κB-mediated production of the pro-inflammatory cytokine TNF-α in LPS-stimulated peritoneal macrophages. Moreover, compound B4 significantly ameliorated 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis symptoms, including body weight loss, colonic pathological damage and inflammatory cell infiltration. The results of western blotting and luciferase reporter assays indicated that compound B4 activated PPAR-γ and subsequently suppressed NF-κB activation. Conversely, the addition of the PPAR-γ antagonist GW9662 abrogated the anti-inflammatory effects of compound B4 both in vitro and in vivo. In summary, compound B4 activated the PPAR-γ pathway to inhibit downstream NF-κB signaling, which alleviated experimental colitis. Thus, this compound may serve as a potential therapeutic agent for patients with CD.

Regioselective Fluorination of Imidazo[1,2-a]pyridines with Selectfluor in Aqueous Condition.

A regioselective synthesis of 3-fluorinated imidazo[1,2-a]pyridines using 1-chloromethyl-4-fluoro-1,4-diazoniabi cyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor) as the fluorinating reagent in aqueous condition is described. In the presence of DMAP, the reaction mainly gave monofluorinated product via electrophilic fluorinated process in moderate to good yields.

Endovascular management of giant middle cerebral artery aneurysms.

BACKGROUND: This article reported the experience of endovascular treatment in giant middle cerebral artery (MCA) aneurysms with parent artery occlusion or stent-assisted coiling. MATERIAL AND METHODS: Eleven consecutive patients with giant MCA aneurysms were included. The aneurysms predominantly involved the M1 segment in two cases, bifurcation in four cases, and M2 in five cases. Four M2 fusiform aneurysms were treated with parent artery sacrifice after balloon occlusion test. The seven unruptured aneurysms and one ruptured one were treated with stent-assisted coiling. The post-operation and long-term follow-up angiographic and clinical outcomes were analyzed. RESULTS: Endovascular coiling was performed successfully in all 11 cases. All four M2 fusiform cases using parent artery occlusion strategy achieved complete occlusion of aneurysms. In the seven cases with stent-assisted coiling, four were completely occluded, two were partially occluded and one remained small residue. Mild perioperative complications occurred in six patients. The follow-up angiography taken at a mean of 13.5 months of eight patients showed that seven aneurysms remained stable or improved and one M1 aneurysms relapsed and needed further treatment. CONCLUSION: Stent-assisted coiling or parent artery occlusion of selected giant MCA aneurysms is an option to consider.

Gold(I)-catalyzed diazo cross-coupling: a selective and ligand-controlled denitrogenation/cyclization cascade.

An unprecedented gold-catalyzed ligand-controlled cross-coupling of diazo compounds by sequential selective denitrogenation and cyclization affords N-substituted pyrazoles in a position-switchable mode. This novel transformation features selective decomposition of one diazo moiety and simultaneous preservation of the other one from two substrates. Notably, the choice of the ancillary ligand to the gold complex plays a pivotal role on the chemo- and regioselectivity of the reactions.

Endovascular coil embolization of aneurysm neck for the treatment of ruptured intracranial aneurysm with bleb formation.

BACKGROUND: Ruptured intracranial aneurysm (ICA) with bleb formation (RICABF) is a special type of ruptured ICA. However, the exact role and effectiveness of endovascular coil embolization (ECE) in RICABF is unknown. We aimed to investigate the effectiveness and safety of ECE of aneurysm neck for RICABF treatment. MATERIAL AND METHODS: We retrospectively assessed consecutive patients who were hospitalized in our endovascular intervention center between October 2004 and May 2012. Overall, 86 patients underwent ECE of aneurysm neck for 86 RICABF. Treatments outcomes included secondary rupture/bleeding rate, aneurysm neck embolization rate, residual/recurrent aneurysm, intraoperative incidents, and post-embolization complications, as well as improvements in the Glasgow outcome scale (extended) (GOS-E). RESULTS: Complete occlusion was achieved in 72 aneurysms (72/86, 83.7%), while 12 aneurysms (12/86, 14.0%) had a residual neck, and 2 aneurysms (2/86, 2.3%) had a residual aneurysm. The postoperative GOS-E was 3 in 3 patients (3.5%), 4 in 10 patients (11.6%), and 5 in 73 patients (84.9%). Follow-up angiography was performed in all patients (mean 9.0 months, interquartile range of 9.0). Recurrence was found in 3 patients (3/86, 3.5%). No aneurysm rupture or bleeding was reported. CONCLUSIONS: Our mid-term follow-up study showed that ECE of aneurysm neck was an effective and safe treatment modality for RICABF. The long-term effectiveness and safety of this interventional radiology technique need to be investigated in prospective and comparative studies.

(3,5-Dimethyl-1H-pyrazol-1-yl){3-[(3,5-dimethyl-1H-pyrazol-1-yl)carbon-yl]-5-methyl-indolizin-1-yl}methanone.

There are two independent mol-ecules in the asymmetric unit of the title compound, C21H21N5O2. In each mol-ecule, the indolizine ring system is essentially planar, with r.m.s. deviations of 0.030 and 0.028 Å. The dihedral angles between the indolizine ring system and the pyrazole rings are 54.7 (3) and 8.6 (3)° in one mol-ecule and 54.4 (3) and 6.6 (3)° in the other. In the crystal, weak C-H⋯O and C-H⋯N hydrogen bonds link mol-ecules, forming a two-dimensional network parallel to (100).

1-[(3,5-Dimethyl-1H-pyrazol-1-yl)carbon-yl]-5-methyl-indolizine-3-carbo-nitrile.

In the title mol-ecule, C16H14N4O, the indolizine ring system is essentially planar, with a maximum deviation of 0.013 (3) Å, and forms a dihedral angle of 7.52 (12)° with the pyrazole ring. In the crystal, weak C-H⋯O hydrogen bonds and π-π stacking inter-actions, with a centroid-centroid distance of 3.6378 (16) Å, link mol-ecules along [001].

Ethyl 3-benzoyl-indolizine-1-carboxyl-ate.

The title compound, C(18)H(15)NO(3), consists of an indolizine ring system and an aromatic ring. The two ring systems are not coplanar, the dihedral angle between the two being 54.26 (7)°. In the crystal, inversion dimers are formed by weak C-H⋯O interactions. These dimeric groups are further extended to form a regular two-dimensional structure by additional weak C-H⋯O inter-actions.

Diethyl indolizine-1,3-dicarboxyl-ate.

The title compound, C(14)H(15)NO(4), was prepared by a 1,3-dipolar cyclo-addition from N-(eth-oxy-carbonyl-methy)pyridinium bromide and ethyl acrylate. The -CO(2) side chains form dihedral angles of 0.2 (3) and 2.4 (3)° with respect to the ring system. In the crystal, two neighbouring mol-ecules form a dimer through weak C-H⋯O interactions. The dimers form a three-dimensional structure via further weak C-H⋯O inter-actions.

(9H-Carbazol-9-ylmeth-yl)diethyl-amine.

The asymmetric unit of the title compound, C(17)H(20)N(2), contains two mol-ecules, whose bond lengths and angles differ only slightly. In the crystal, neighbouring mol-ecules form pillar structures via edge-to-face π-π stacking inter-actions [edge-to-face distances = 3.538 (3) and 3.496 (3)Å].

Dimethyl 9-benzyl-3-cyano-9H-pyrrolo[1,2-a]benzimidazole-1,2-dicarboxyl-ate.

The title compound, C(22)H(17)N(3)O(4), was prepared through 1,3-dipolar cyclo-addition: the dihedral angle between the benzimidazole and benzene rings is 80.93 (6)°. The crystal structure is stabilized by weak π-π inter-actions between the planar pyrrolobenzimidazole rings (r.m.s. deviation = 0.0293 Å) of neighbouring mol-ecules, forming chains along the c axis. The perpendicular distance is 3.47 (2) Šand the centroid-centroid distances are in the range of 3.590 (3)-3.944 (3) Å.

(Pyridine-2,6-diyldimethyl-ene)bis-(diphenyl-methanol).

In the title compound, C(33)H(29)NO(2), the central pyridyl ring makes dihedral angles of 42.71 (16), 44.78 (16), 85.47 (12) and 76.74 (12)° with the four phenyl rings. There are two intra-molecular O-H⋯N hydrogen bonds. In the crystal structure, mol-ecules are linked into a chain running along the b axis by a weak C-H⋯π inter-action.

2-(6-Methyl-2-pyrid-yl)-1,1-diphenyl-ethanol.

The title compound, C(20)H(19)NO, was prepared from 2,6-lutidine and benzophenone. There are two symmetry-independent mol-ecules in the asymmetric unit. Each mol-ecule is involved in one intra-molecular O-H⋯N hydrogen bond. In the crystal structure, helical chains are formed along the b axis by weak π-π inter-actions between neighbouring mol-ecules [centroid-centroid distances between the pyridyl rings of the two independent mol-ecules = 4.041 (3) and 4.051 (3) Å].