Direct Synthesis for Benzofuro[3,2-d]pyrimidin-2-Amines via One-Pot Cascade [4 + 2] Annulation/Aromatization between Benzofuran-Derived Azadienes and Carbodiimide Anions.

The chemoselective [4+2] annulation/aromatization reactions between benzofuran-derived azadienes and N-Ts cyanamides are developed, affording a convenient method for synthesizing benzofuro[3,2-d]pyrimidin-2-amines under mild conditions. Herein, N-Ts cyanamides selectively participated in reactions absolutely via carbodiimide anion intermediates and the corresponding cyanamide anion intermediates derived products were not observed. The proposed chemoselective stepwise reaction mechanism was well supported by DFT calculations.

Synthesis of Five-Membered Cyclic Guanidines via Cascade [3 + 2] Cycloaddition of α-Haloamides with Organo-cyanamides.

The convenient preparation of N2-unprotected five-membered cyclic guanidines was achieved through a cascade [3 + 2] cycloaddition between organo-cyanamides and α-haloamides under mild conditions in good to excellent yields (up to 99%). The corresponding cyclic guanidines could be easily transformed into hydantoins via hydrolysis.

Recent advances in 1,4-functional group migration-mediated radical fluoroalkylation of alkenes and alkynes.

Recently, the combination of radical fluoroalkylation of alkenyl or alkynyl moieties and 1,4-functional group migration (1,4-FGM) has emerged as a powerful strategy for the synthesis of fluorine-containing compounds. In this article, some representative reactions of 1,4-FGM-mediated radical fluoroalkylation of N-(arylsulfonyl)acrylamides, tertiary alcohol-containing alkynes, tertiary alcohol-containing alkenes and intermolecular 1,4-FGM-type substrates have been discussed based on the types of substrates.

Copper-catalyzed C-H/N-H cross-coupling reactions for the synthesis of 3-heteroaryl quinoxalin-2(1H)-ones.

An effective copper-catalyzed direct C-H/N-H cross-coupling of quinoxalin-2(1H)-ones with diverse unprotected 2-quinoxalinones and 2-quinolinones has been developed. This protocol provides a convenient route, with broad substrate scope, good functional group tolerance, and high atom economy, to various important quinoxalin-2(1H)-one-containing biheteroaryls, which are privileged structures in many biologically active compounds.

Synthesis of spirobarbiturate-pyrrolidinones via a domino aza-Michael/SN2 cyclization of barbiturate-derived alkenes with N-alkoxy α-haloamides.

A highly efficient domino aza-MIRC (Michael Induced Ring Closure) reaction between barbiturate-derived alkenes and N-alkoxy α-haloamides has been achieved in moderate to excellent yields. This reaction proceeds smoothly under mild conditions via a domino aza-Michael addition/intramolecular SN2 sequence, providing a practical tool in the synthesis of bioactive molecules spirobarbiturate-3-pyrrolidinones.

Asymmetric Synthesis of Chiral Spiroketal Bisphosphine Ligands and Their Application in Enantioselective Olefin Hydrogenation.

A series of chiral spiroketal bisphosphine ligands containing 1,1'-spirobi(3 H,3' H)isobenzofuran backbones was accessed through asymmetric synthesis and subsequently tested in enantioselective Rh-catalyzed hydrogenation of α-dehydroamino acid esters. The ligand providing the highest enantioselectivity (up to 99.5%) was obtained in seven steps in an overall 38% yield. The synthesis could be performed on a gram scale, and no kinetic resolution of enantiomers is required. Overall, the developed ligand provides an easily accessible alternative to SDP ligands as well as other chiral bisphosphine ligands.

Organocatalytic Aza-Michael/Michael Cyclization Cascade Reaction: Enantioselective Synthesis of Spiro-oxindole Piperidin-2-one Derivatives.

A simple, direct, and highly enantioselective synthesis of spiro-oxindole piperidin-2-one derivatives was achieved through an aza-Michael/Michael cyclization cascade sequence using a squaramide catalyst. The desired products were obtained in excellent yields (up to 99%) and good to high stereoselectivities (up to >20:1 dr and up to 99% ee) under mild conditions.

Synthesis of Sulfamate-Fused 2-Aminopyrroles via an Isocyanide-Based Three Component [1+2+2] Annulation.

An efficient preparation of sulfamate-fused 2-aminopyrroles was achieved through an isocyanide-based three-component [1+2+2] annulation of isocyanides, dialkyl acetylenedicarboxylates, and sulfamate-derived cyclic imines in good to excellent yields (up to 99 %). This reaction proceeds smoothly without any activation or modification of substances under neutral and metal-free conditions. The reaction could also be conveniently performed on a gram scale.

Asymmetric Organocatalytic [4 + 1] Annulations: Enantioselective Construction of Multifunctionalized Spirocyclopentane Oxindoles Bearing α,α-Disubstituted α-Amino-ß-keto Esters.

The highly enantioselective preparation of spirooxindoles bearing α,α-disubstituted α-amino-ß-keto esters was achieved through [4 + 1] annulation of oxindoles and α-imine-ß-oxo-γ,δ-unsaturated esters under mild conditions in good yields (up to 82%) and stereoselectivities (up to >20:1 dr, 96% ee). The reaction is amenable to gram scale synthesis using catalyst loading as low as 1 mol %. The corresponding chiral α,α-disubstituted α-amino-ß-keto esters could be easily transformed into cyclopenta[ b]indole derivatives without erosion of enantiopurity.

Asymmetric Total Syntheses of (-)-α-Lycorane, (-)-Zephyranthine, and Formal Synthesis of (+)-Clivonine.

An asymmetric route to (-)-α-lycorane and (-)-zephyranthine, and a formal total synthesis of (+)-clivonine were achieved. A pivotal intermediate, which serves as a potent precursor for the divergent syntheses of these natural products, was accessed by a diastereoselective Pd-catalyzed cinnamylation of an N-tert-butanesulfinyl imine.

Reconstructive endovascular treatment of vertebral artery dissecting aneurysms with the Low-profile Visualized Intraluminal Support (LVIS) device.

INTRODUCTION: The Low-profile Visualized Intraluminal Support (LVIS) device is a new generation of self-expanding braided stent recently introduced in China for stent assisted coiling of intracranial aneurysms. The aim of our study is to evaluate the feasibility, safety, and efficacy of the LVIS device in reconstructive treatment of vertebral artery dissecting aneurysms (VADAs). METHODS: We retrospectively reviewed the neurointerventional database of our institution from June 2014 to May 2016. Patients who underwent endovascular treatment of VADAs with LVIS stents were included in this study. Clinical presentation, aneurysmal characteristics, technical feasibility, procedural complications, and angiographic and clinical follow-up results were evaluated. RESULTS: 38 patients with VADAs who underwent treatment with LVIS stent were identified, including 3 ruptured VADAs. All VADAs were successfully treated with reconstructive techniques including the stent-assisted coiling (n = 34) and stenting only (n = 4). Post-procedural complications developed in 3 patients (7.9%) including two small brainstem infarctions and one delayed thromboembolic event. Complications resulted in one case of minor permanent morbidity (2.6%). There was no procedure-related mortality. The follow-up angiogram was available in 30 patients at an average of 8.3 months (range, 2 to 30 months), which revealed complete occlusion in 23 patients (76.7%), residual neck in five patients (16.7%), and residual sac in two patients (6.7%). The follow-up of 25 aneurysms with incomplete immediate occlusion revealed 22 aneurysms (88%) with improvement in the Raymond class. One aneurysm (3.3%) showed recanalization and required retreatment. Clinical followed-up at 5-28 months (mean 14.1 months) was achieved in 36 patients because two patients died of pancreatic cancer and basal ganglia hemorrhage, respectively. No new neurologic deterioration or aneurysm (re)bleeding was observed. CONCLUSIONS: Our preliminary experience with reconstruction of VADAs with the LVIS device demonstrates that this treatment approach is feasible with good short-term angiographic and clinical outcomes. Long-term and larger cohort studies are necessary to determine long-term outcomes of this therapy.

Endovascular Treatment of 48 Early Branch Aneurysms of the Middle Cerebral Artery.

OBJECTIVE: To evaluate the feasibility of endovascular treatment (EVT) for early branch aneurysms (EBAs) of the middle cerebral artery (MCA). METHODS: We reviewed 211 MCA aneurysms that received EVT between January 2012 and December 2014. The EBAs were identified according to their special patterns on cerebral angiography. The angiographic features, clinical outcomes, and angiographic results were investigated. RESULTS: Forty-eight EBAs (22.7%) in 47 patients were identified among the MCA aneurysms. The treatments were successful in all EBAs, including coiling in 23 aneurysms, balloon-assisted coiling in 4, and stent-assisted coiling in 21. Immediate angiograms showed complete occlusion in 15 aneurysms, residual neck in 18, and residual aneurysm in 15. A procedure-related complication occurred in 1 patient (2.1%) who experienced rebleeding during treatment, and no neurologic function was insulted. Thirty-nine patients underwent angiographic follow-up (mean, 8.2 months), which showed 36 aneurysms were not aggravated, 3 had minor recanalization, and none showed major recanalization. The clinical follow-up (mean, 22.8 months) of all patients demonstrated no neurologic deterioration or rebleeding; however, 1 patient died of unexplained cerebral hemorrhage. CONCLUSIONS: Preliminary experience demonstrates that EVT for EBAs is feasible and safe. Direct comparison of clipping and coiling is warranted.

Copper-catalyzed asymmetric hydroboration of α-dehydroamino acid derivatives: facile synthesis of chiral ß-hydroxy-α-amino acids.

The Cu-catalyzed asymmetric conjugate hydroboration reaction of ß-substituted α-dehydroamino acid derivatives has been established, affording enantioenriched syn- and anti-ß-boronate-α-amino acid derivatives with excellent combined yields (83-99%, dr ≈ 1:1) and excellent enantioselectivities (92-98% ee). The hydroboration products were expediently converted into valuable ß-hydroxy-α-amino acid derivatives, which were widely used in the preparation of chiral drugs and bioactive molecules.