Periodic Reporting for period 2 - Foldmetcat (Bioinspired Catalytic Metallofoldamers) Reporting period: 2021-03-01 to 2022-08-31 Summary of the context and overall objectives of the project The aim of this proposal is to design new types of catalysts containing electrophilic transition metal centers to simultaneously fold and activate polyunsaturated substrates promoting non-inherent cyclization modes.Our goal, inspired by mimicking the characteristics of terpenoid cyclase enzymes, is unprecedented, although it is rooted on fundamental organometallic chemistry. Although our most of work will be carried out with gold catalysts, another goal of this research is to develop other general-purpose efficient chiral electrophilic catalysts based on different metals. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far A significant part of our research work has been focused on the design and synthesis of new chiral catalysts based on Johnphos-type ligands as well as related complexes based on chiral planar ferrocene ligands. These new catalysts have allowed to perform enantioselectively important cyclization reactions and to develop an atroposelective synthesis of aryl-substituted indole derivatives. In addition, new digold complexes derived from cavitands have been found to catalyze enantioselectively the alkoxycyclization of 1,6-enynes, which has been applied in the first total synthesis of the natural product mafaicheenamine C. A new family of catalysts with ligands bearing urea, thiourea, and squaramide subunits have been designed for the silver-free gold-catalyzed enantioselective folding of unsaturated substrates. This has led to the development of the new concept of H‑bonded counterion-directed enantioselective gold(I) catalysis.Small gold(I) and gold(I)-silver(I) clusters have also been synthesized for the activation of alkynes. We have also studied alternative catalysts based on metals different from gold (such as rhodium and zinc). In particular, Rh(II) salts have found to be highly reactive for the generation of the corresponding metal carbenes by decarbenation of substituted cycloheptatrienes.We have also discovered the activation of acetylene gas catalyzed by gold and have studied the oligomerization of acetylene under mild conditions as well as other metathesis-type reactions with electron-rich alkenes. In these transformations, acetylene behaves as a C2 dicarbene unit leading to double cyclopropanations. This method was applied for the first total synthesis of waitziacuminone, which was remarkably completed in a single step. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) Our work on the synthesis and applications of new chiral mono- and binuclear gold catalysts has evolved from a traditional covalent approach to a more modular supramolecular arrangement of the achiral cation and chiral anion. This opens new opportunities for the synthesis of even more complex catalysts for the bio-inspired cyclization of polyunsaturated substrates in a modular manner. Work along these lines is now being explored. Cationic Gold(I)-Cavitand Catalysts. Aplication in total synthesis of carbaxole alkaloids Enantioselectiuve folding of enynes with pyrrolidinylbiphenylphosphine Au Catalysis New chiral gold(I) catalysts
