Periodic Reporting for period 1 - PHOTALLICA (1,2-Dicarbofunctionalization of Alkenes by Merging Photoredox and Transition-Metal Catalysis) Reporting period: 2019-05-01 to 2021-04-30 Summary of the context and overall objectives of the project "Humanity's modern way of living is borne by the production of chemicals, which include functional materials (such as polymers), agrochemicals and pharmaceuticals. Among the H2020 societal challenges, the ""climate action, environment, resource efficiency and raw materials"" item aims to diminish society's chemical footprint. It addresses the importance of developing more efficient, less wasteful and responsible ways for the production of chemical goods. The use of catalytic reactions for the synthesis of molecules has the advantage of being more sustainable, as they have lower energy consumption, shorter reaction times and use less reactive starting materials, among others. In line with this, the discovery of novel catalytic transformations that use feedstock starting materials, such as unsaturated hydrocarbons, is one of the most direct way of accessing functionalized carbon skeletons that are present in value-added molecules. The overarching objective of this project was to develop new chemical reactions for the functionalization of double carbon-carbon bonds using dual transition-metal/photoredox catalysis, aiming for the generation of disubstituted carbon chains in an efficient and mild way. This action delivered two new catalytic transformation using the aforementioned methodology for the synthesis of value-added compounds that can be used to produce for example polymers, agrochemicals or pharmaceuticals." Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far At the start of the project, a new strategy for the difunctionalization of unactivated alkenes using dual transition-metal/photoredox catalysis was studied. Shortly after the start of the action, highly related work was published. Although this clearly demonstrates the importance of the envisioned transformations within this action, the impact of our work (novelty) would be negatively affected. Therefore the course of the action was slightly altered to pursue related yet equally relevant catalytic functionalization reactions of unsaturated C-C bonds. As a result, two new chemical transformations that provide access to substituted carbon skeletons, such as 1,4-aminoalkyl substituted carbon chains for the first project, and α,β-disubstituted γ-butyrolactones and δ-lactams for the second, were developed. These reactions use simple starting materials, mild conditions, and are broadly applicable. Importantly, the obtained products are embedded in molecules that present biological activities, therefore it is expected that the methods will drive industrial innovation and help in the development of new drugs. The results of this project were published in the prestigious journal Nature Catalysis, disseminated via the website and twitter account of the publisher, the host research group and university. A press release was written for both publications.Project 1: Catalytic radical generation of π-allylpalladium complexes, published in Nature Catalysis, Year 2020, Volume 3, Pages 393–400.Project 2: Diastereodivergent synthesis of enantioenriched α,β-disubstituted γ-butyrolactones via cooperative N-heterocyclic carbene and Ir catalysis. Nature Catalysis, Year 2020, Volume 3, Pages 48–54. 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) The synthetic methodologies developed in this project contribute to the advancement of the field of catalysis and provide novel approaches for the synthesis of value-added molecules. In the first project, a new way for the preparation of allylic amines was developed using feedstock materials -such as butadiene- and bifunctional reagents that lower the generation of waste. The products are formed under mild conditions by a palladium catalyst that is activated by visible light. The activated catalysts reacts with the starting materials to generate radicals and form a key intermediate -the so-called π-allylpalladium complex-. This intermediate had previoulsy only been obtained using ionic mechanisms, which generally require prefunctionalized starting materials or stoichiometric oxidants, as well as harsh conditions that limit its applicability. Because this complex is also formed in other boardly-applicable palladium-catalysed allylic functionalization reactions, the developed method will open up new opportunities for the formation of C-C and C-heteroatom bonds. Additionally, given the importance of the substitution pattern of the products, it is foreseen that the method will contribute to drive industrial innovation and find use for example, in the synthesis of drug candidates that improve human health.A system based on two chiral catalysts working hand-in-hand was develop for the second project. The novel chemical transformation targeted the synthesis of all four stereoisomers of so-called α,β-disubstituted γ-butyrolactones, which are moieties present in numerous biologically-relevant molecules. The key to success was the use of a cooperative catalytic system based on an iridium catalyst and a N-heterocyclic carbene organocatalysts. The modularity of the catalytic system resulted in the selective production of one of the four stereoisomers of the product, depending on the reaction conditions, at will. Before this work, the field of dual metal/NHC organocatalysis was limited to the use of palladium as the transition-metal catalyst, limiting its applicability to certain starting materials. Now, by using iridium as the catalyst, new building blocks can be employed as starting point. The products formed in the reaction are highly valuable motifs that are present in the core of numerous natural products displaying a wide range of biological activities. For example pilocarpin, a drug used to treat glaucoma. It is foreseen that the work will aid in the discovery of pharmaeutical compounds and inspire the discovery of new dual catalytic systems based on organocatalysis and transition-metal cataylsis, as well as new stereodivergent asymmetric transformations. Graphic summary of the two developed projects.