Design of new redox processes: Enatioselective reactions based on Chiral-Rhodium Catalysis and use of sulfinate salts

Resumen

When considering the employment of reactive radical species in organic synthesis, it is astonishing the mildness which photo and electro reactions required to handle them. In fact, relevant toxic radical initiators can be easily substituted by catalytic amounts of a photocatalyst or by the use of “green” electrons. With this perspective, the last decade has evidenced the powerful of such methods by the publication of uncountable strategies. In this sense, the first part of this PhD thesis will focus on the design of photocatalytic protocols to access valuable cyclic structures, as 1-pyrroline and alicyclic β amino carbonyl derivatives. Both strategies emerge by the combination of rhodium-chiral catalysis and photoredox catalysis. In chapter 2.1 the strategy involves the distal functionalization of acyl heterocycles through a hydrogen-atom transfer (HAT) process and the use of tailor-made ketimines as reliable electrophilic partners. This transformation is translated into an enantiomerically controlled radical/polar cascade reaction in which water is produced as the sole by-product and stereoselectivity is dictated by coordination to a chiral-at-rhodium catalyst. In chapter 2.2 the overall reactivity relies on the performance of the substrate-catalyst complex to assist both the enantiocontrol and the photoredox tasks. This transformation led to an enantioselective [3 + 2] photocycloaddition between coordinated α,β-unsaturated acyl imidazoles and cyclopropylamine derivatives. Successively, the focus of the thesis is directed toward the design of new valuable redox transformations based on single-electron oxidation of sulfinate salts. Their dual nature as alkylating or sulfonylating agents is employed for the photoflow functionalisation of heteroarenes and the electrosynthesis of allyl sulfones. In chapter 3.4 the protocol relies on the in situ generation and further in-line use of alkyl zinc sulfinates through a continuous-flow system. The environmentally friendly character of the protocol is assured by the use of a green solvent mixture, the presence of a metal free oxidant and low waste generation. In chapter 3.5 the protocol starts with the anodic oxidation of the sodium sulfinate, then the radical addition to the alkene is followed by the elimination of the trifluoroborate moiety, giving rise to a variety of differently substituted allyl sulfones. The process transpires under very mild and simple reaction conditions that can even take place using water as solvent and in absence of additional electrolytes, which provides a general, appealing and low-cost methodology for the synthesis of allyl sulfones