Redox-Neutral and Atom-Economic Route to ß-Carbolines via Gold-Catalyzed [4 + 2] Cycloaddition of Indolylynamides and Cyanamides.

Gold(I)-catalyzed [4 + 2] cycloaddition of indolylynamides and cyanamides (aminonitriles) is an efficient redox-neutral and atom-economic route to diversely substituted 1,3-diamino-ß-carbolines. The protocol operates under mild conditions (Ph3PAuNTf2 5 mol %, DCE, 60 °C) with a good tolerance to functional groups (23 examples and yields up to 98%). The obtained ß-carboline systems represent a versatile synthetic platform with modifiable substituents for successive functionalizations. Control experiments indicate the crucial role of both the nature of reactants and the identity of employed catalysts in the developed cycloaddition.

Gold-Catalyzed Nitrene Transfer from Benzofuroxans to N-Allylynamides: Synthesis of 3-Azabicyclo[3.1.0]hexanes.

The gold-catalyzed reaction between benzofuroxans, functioning as nitrene transfer reagents, and N-allylynamides leads to 3-azabicyclo[3.1.0]hexan-2-imines. This highly selective annulation proceeds smoothly under mild conditions (5 mol % Ph3PAuNTf2, PhCl, 60 °C) and exhibits high functional group tolerance (21 examples, ≤96% yields). The obtained cyclopropanated products represent a useful synthetic platform with an easily modulated substitution pattern as illustrated by their postmodifications. Intramolecular cyclopropanation of gold α-imino carbene intermediates is suggested as a key step of the catalytic cycle.

Hetero-Tetradehydro-Diels-Alder Cycloaddition of Enynamides and Cyanamides: Gold-Catalyzed Generation of Diversely Substituted 2,6-Diaminopyridines.

Gold(I)-catalyzed hetero-tetradehydro-Diels-Alder cycloaddition of enynamides and cyanamides comprises an efficient route to diversely substituted 2,6-diaminopyridines (28 examples; yields up to 99%). The reaction proceeds under very mild conditions (DCM, rt) with high functional group tolerance. The obtained 2,6-diaminopyridines represent a useful synthetic platform with an easily modulated substitution pattern for subsequent functionalizations of both the pyridine core and the N-substituents.

Acid-catalyzed [2 + 2 + 2] cycloaddition of two cyanamides and one ynamide: highly regioselective synthesis of 2,4,6-triaminopyrimidines.

Triflic acid (10 mol%) catalyzes the highly regioselective [2 + 2 + 2] cycloaddition between two cyanamides and one ynamide to grant the 2,4,6-triaminopyrimidine core. The developed synthetic method is effective for the preparation of a family of the diversely substituted heterocyclic products (30 examples; yields up to 94%). The synthesis can be easily scaled up and conducted in gram quantities. As demonstrated by the post-functionalizations involving the amino-substituents, the obtained heterocycles represent a useful platform for the construction of miscellaneous pyrimidine-based frameworks. The performed density functional theory calculations verified a particular role of H+, functioning as an electrophilic activator, in the regioselectivity of the cycloaddition.

Nature of the Nucleophilic Oxygenation Reagent Is Key to Acid-Free Gold-Catalyzed Conversion of Terminal and Internal Alkynes to 1,2-Dicarbonyls.

2,3-Dichloropyridine N-oxide, a novel oxygen transfer reagent, allows the conductance of the gold(I)-catalyzed oxidation of alkynes to 1,2-dicarbonyls in the absence of any acid additives and under mild conditions to furnish the target species, including those derivatized by highly acid-sensitive groups. The developed strategy is effective for a wide range of alkyne substrates such as terminal- and internal alkynes, ynamides, alkynyl ethers/thioethers, and even unsubstituted acetylene (40 examples; yields up to 99%). The oxidation was successfully integrated into the trapping of reactive dicarbonyls by one-pot heterocyclization and into the synthesis of six-membered azaheterocycles. This synthetic acid-free route was also successfully applied for the total synthesis of a natural 1,2-diketone.

The Urology Residency Program in Israel-Results of a Residents Survey and Insights for the Future.

OBJECTIVE: Urology practice has undergone several changes in recent years mainly related to novel technologies introduced. We aimed to get the residents' perspective on the current residency program in Israel and propose changes in it. METHODS: A web-based survey was distributed among urology residents. RESULTS: 61 residents completed the survey out of 95 to whom it was sent (64% compliance). A total of 30% replied that the 9 months of mandatory general surgery rotation contributed to their training, 48% replied it should be shortened/canceled, and 43% replied that the Step A exam (a mandatory written certifying exam) in general surgery was relevant to their training. A total of 37% thought that surgical exposure during the residency was adequate, and 28% considered their training "hands-on." Most non-junior residents (post-graduate year 3 and beyond) reported being able to perform simple procedures such as circumcision and transurethral resections but not complex procedures such as radical and laparoscopic procedures. A total of 41% of non-junior residents practice at a urology clinic. A total of 62% of residents from centers with no robotics replied its absence harmed their training, and 85% replied they would benefit from a robotics rotation. A total of 61% of residents from centers with robotics replied its presence harmed their training, and 72% replied they would benefit from an open surgery rotation. A total of 82% of the residents participated in post-graduate courses, and 81% replied they would engage in a clinical fellowship. CONCLUSION: Given the survey results we propose some changes to be considered in the residency program. These include changes in the general surgery rotation and exam, better surgical training, possible exchange rotations to expose residents to robotic and open surgery (depending on the availability of robotics in their center), greater out-patient urology clinic exposure, and possible changes in the basic science period.

A urologic stethoscope? Urologist performed sonography using a pocket-size ultrasound device in the point-of-care setting.

PURPOSE: Ultrasound is commonly used in urology. Technical advances with reduced size and cost led to diffusion of small ultrasound devices to many clinical settings. Even so, most ultrasound studies are performed by non-urologists. We aimed to evaluate the utility of a pocket-size ultrasound device (Vscan™ GE Healthcare) and the quality of urologist performed study. METHODS: Three consecutive studies were performed: (1) a urologist using the pocket ultrasound, (2) a sonographist using the pocket ultrasound, and (3) a sonographist using a standard ultrasound device. Thirty-six patients were evaluated with a basic urologic ultrasound study. An excepted deviation between studies was preset for numeric parameters and t test performed. Ordinal parameters were analyzed using Cohen's kappa coefficient. RESULTS: Kidney length, renal pelvis length, renal cyst diameter, post-void residual and prostate volume (transabdominal) differences were found to be insignificant when comparing a urologist pocket ultrasound study to a sonographist standard ultrasound study (P = 0.15; P = 0.21; P = 0.81; P = 0.32; P = 0.07, respectively). Hydronpehrosis evaluation (none, mild, moderate and severe) and the presence of ureteral jet signs conferred a high inter-observer agreement when comparing the above studies using the Cohen's kappa coefficient (K = 0.63; K = 0.62, respectively). CONCLUSIONS: Urologist performed pocket ultrasound study is valid in evaluating the upper and lower urinary tract and is practical in many clinical scenarios. The urologic stethoscope is now becoming a reality within reach.