Design of Modern Approaches for the (Asymmetric) Synthesis of Original Fluorinated Molecules

这一合作项目旨在开发新的和现代的方法来合成前所未有的氟化分子。含氟基序在有机化学中，即在农用化学和药物活性成分中具有重要意义。事实上，被新出现的氟化基团取代的目标化合物将通过极大地扩展氟化分子的化学空间而在该领域取得新的进展，因为到目前为止这是一个未知的研究领域。为了达到这一具有挑战性的目标，基于光催化(WP1)和不对称阴离子结合(WP2)策略的两种互补方法被设想。对于这两种方法，将设计和合成创新的中性和阳离子一氟/二氟甲基化和二氟甲基硫醇试剂，为以后在将要开发的催化方法中的实施提供所需的平台。因此，在WP1中，将寻求具有二氟甲基化和二氟甲硫醇化来源的苄基C(SP3)-H键的选择性官能化。或者，在WP2对映体选择性氟甲基化、二氟甲基化和二氟甲硫化方法中，使用不同的亲手性亲核试剂，包括亲电阳离子试剂的催化阴离子结合激活，将被开发。有机氟化学(Besset、合成方法和原始试剂的设计)和光催化或有机催化(García Maneño、有机光催化剂设计和阴离子结合方法)方面的专业知识相结合，对于解决这一具有挑战性的项目至关重要。AsymFluoChem项目的成功将丰富化学家的工具箱，使其能够使用现代技术合成前所未有的非手性和对映体富集型分子。此外，还将在有机氟化学、有机催化和光化学方面开发新的视角，这些都是学术界和化学工业应用中非常感兴趣的领域。

This collaborative project aims at developing novel and modern approaches towards the synthesis of unprecedented fluorinated molecules. Fluorinated motifs are important in organic chemistry, namely in agrochemical and pharmaceutical active ingredients. Indeed, the targeted compounds substituted with emergent fluorinated groups will allow for new advances in the field by expanding considerably the chemical space of fluorinated molecules as so far this is an uncharted research area. To reach that challenging goal, two complementary approaches based on photocatalysis (WP1) and asymmetric anion-binding (WP2) strategies are envisioned. For both approaches, the design and synthesis of innovative neutral and cationic mono-/difluoromethylating and difluoromethylthiolating reagents will be carried out, providing the required platform for the later implementation in the catalytic methods to be developed. Hence, in WP1 the selective functionalization of benzylic C(sp3)-H bonds with difluoromethylating and difluoromethylthiolating sources will be pursued. Alternatively, in WP2 enantioselective fluoromethylation, difluoromethylation and difluoromethylthiolation methods using different pro-chiral nucleophiles, embracing a catalytic anion-binding activation of electrophilic cationic reagents, will be developed. The combination of the expertise in organofluorine chemistry (Besset, synthetic methodologies and design of original reagents) and photo- or organocatalysis (García Mancheño, organophotocatalysts design and anion-binding methodologies) is essential in tackling this challenging venture. The success of the AsymFluoChem project will enrich the chemist’s toolbox with methods allowing the synthesis of unprecedented both non-chiral and enantioenriched molecules using modern technologies. Furthermore, novel perspectives in organofluorine chemistry, organocatalysis and photochemistry will be developed, which are of great interest in academia and for chemical industry applications.