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In the second year of funding from the Petroleum Research Fund, we aimed to improve the cycloaddition chemistry discovered during the first year and generalize the process for use in the preparation of complex molecules (ie. 1 → 2). Unfortunately, attempts to improve the efficiency of this, and related transformations, were unsuccessful.

At about the same time, my research group was focusing upon the development of new methods utilizing visible light activated photocatalysts for organic synthesis. Using support from the Petroleum Research Fund, we have published 2 manuscripts during the past year, with two additional manuscripts currently under review. On the basis of observations made during the early stages of our research in this area, we were able to develop an oxidative aza-Henry reaction using photoredox catalysis [J. Am. Chem. Soc. 2010, 132, 1464]. This extraordinarily straightforward method was performed by simply dissolving the desired tertiary amine 3 in nitromethane with 1 mol % of known Ir catalyst and irradiating with a hand held compact fluorescent light source for up to 18 h, providing 4 in excellent yield. We were able to expand the utility of photoredox catalysis as a means to initiate radical reactions with the development of a new methodology for the cyclization of a-bromomalonates and imides onto indoles and pyrroles [Org. Lett. 2010, 12, 368]. In particular, this mild, catalytic method (1 mol% Ru) efficiently converted affected a cascade radical cyclization of 5, providing the tetracyclic product 6 in 79% yield as a single diastereoisomer. We have recently developed intermolecular radical coupling strategies which provide rapid access to indole alkaloid scaffolds from readily available bromopyrroloindolines such as 7. The coupling of 7 with 8 in the presence of 2.5 mol % of Ru catalyst provided the desired coupling product, 9, in 84% isolated yield. Available in only 3 steps from commercially available material, 9 is expected to be the common intermediate in the synthesis of the bisindole alkaloid family of natural products. Finally, we have developed a catalytic variant of the Appel reaction using photoredox catalysis. The stoichiometric reductant Ph₃P can be replaced by 1 mol % of the Ru catalyst and visible light irradiation, providing bromides or iodides in high chemical yield under mild reaction conditions. This method constitutes a new approach to catalytic carbon-oxygen bond activation which we are currently investigating for nucleophilic displacement chemistry.