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Transition-metal catalysis has revolutionized the field of organic synthesis by facilitating the construction of complex organic molecules in a highly efficient manner. Although these catalysts are typically based on precious metals, researchers have made great strides in discovering new base metal catalysts over the past decade. This Account describes our efforts in this area and details the development of versatile Ni complexes that catalyze a variety of cycloaddition reactions to afford interesting carbocycles and heterocycles. First, we describe our early work in investigating the efficacy of N-heterocyclic carbene (NHC) ligands in Ni-catalyzed cycloaddition reactions with carbon dioxide and isocyanate. The use of sterically hindered, electron donating NHC ligands in these reactions significantly improved the substrate scope as well as reaction conditions in the syntheses of a variety of pyrones and pyridones. The high reactivity and versatility of these unique Ni(NHC) catalytic systems allowed us to develop unprecedented Ni-catalyzed cycloadditions that were unexplored due to the inefficacy of early Ni catalysts to promote hetero-oxidative coupling steps. We describe the development and mechanistic analysis of Ni/NHC catalysts that couple diynes and nitriles to form pyridines. Kinetic studies and stoichiometric reactions confirmed a hetero-oxidative coupling pathway associated with this Ni-catalyzed cycloaddition. We then describe a series of new substrates for Ni-catalyzed cycloaddition reactions such as vinylcyclopropanes, aldehydes, ketones, tropones, 3-azetidinones, and 3-oxetanones. In reactions with vinycyclopropanes and tropones, DFT calculations reveal noteworthy mechanistic steps such as a C-C σ-bond activation and an 8π-insertion of vinylcyclopropane and tropone, respectively. Similarly, the cycloaddition of 3-azetidinones and 3-oxetanones also requires Ni-catalyzed C-C σ-bond activation to form N- and O-containing heterocycles.

Percutaneous transcatheter closure of ruptured sinus of valsalva aneurysm was attempted in eight patients between January 1995 and March 2003 as an alternative strategy to surgery as this technique at present is an accepted therapeutic modality for various intracardiac defects. The age range was 14-35 years, all were male, seven in symptomatic class III and one in class IV on medical treatment. Two-dimensional and color Doppler echocardiography revealed rupture of an aneurysm of right coronary sinus into right ventricle in five and noncoronary sinus into right atrium in three and none had associated ventricular septal defect. The echo estimated size of the defect was 7-12 mm. On cardiac catheterization left ventricular end-diastolic pressure ranged from 20 to 40 mmHg and the calculated Qp/Qs ratio was 2-3.5. In all patients the defect was crossed retrogradely from the aortic side and over an arterio-venous wire loop after balloon sizing, devices were successfully deployed by antegrade venous approach (Rashkind umbrella device in two and Amplatzer occluders in six, which included Amplatzer duct occluder in five and Amplatzer septal occluder in one). One patient who had residual shunt developed hemolysis on the next day and was taken up for reintervention. That patient continued to have intermittent hemolysis and was sent for surgical repair. On follow-up (2-96 months), there was no device embolization, infective endocarditis, and aortic regurgitation. One patient died of progressive congestive heart failure while other six are asymptomatic. These data highlight that transcatheter closure is feasible and effective, especially safe with the available Amplatzer devices. Definitely, it has the advantage of obviating open heart surgery but complete occlusion is mandatory to prevent hemolysis and infective endocarditis.

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