Development And Applications Of Gold-catalyzed Cascade Cyclization Approach Of1,5-Enynes

As multifunctional molecules,1,5-enyne compounds have been used as important building blocks for diversity-oriented organic synthesis. Based on this point of view, we have developed two novel transformations of1,5-enynes catalyzed by gold catalyst, and applied tandem cyclization reactions of1,5-enyne compounds for the total synthesis of natural product. The following two parts are mainly included.First, a novel strategy for the synthesis of multisubstituted naphthalenes was developed via a gold(I)-catalyzed alkyne alkoxylation/dienolether aromaticity-driven cascade cyclization using1,5-enyne substrates. The functional group toleration was examined by synthesizing a series of substrates and the mechanism was also studied based on intermediates isolated through deuterium labeling experiments.Subsequently, an unprecedented gold(I) catalyzed5-endo-dig cyclization of1,5-enyne substrates cascade aerobic oxidative C-H functionalization reaction with molecular oxygen as the oxidant and oxygen source is described. This reaction provides an efficient approach to indenone compounds, which are highly valued chemicals and widely used in the pharmaceutical and chemical industry. The simple conditions and the use of molecular oxygen make this protocol very environmentally friendly and practical.Finally, a formal synthesis of the cytotoxic isoprekinamycin (IPK) that were the rare benzo[a]fluorene class of natural products was performed via gold(I) catalyzed5-endo-dig cyclization of1,5-enyne substrates cascade aerobic oxidative C-H functionalization reaction. Our synthetic strategy of IPK simplified down by three steps from the starting material to key intermediates, which makes the diazobenzo[a]fluorene system attractive for generation of synthetic analogues.