This proposal is dedicated to the development of a new C-H functionalization strategy allowing to selectively create a C-C bond at the terminal position of an alkane fragment. This strategy is based on the ability of group 10 metals to migrate along an alkyl chain via the ß-H elimination/p-complex rotation/insertion mechanism and undergo reductive elimination at the least substituted terminal position. This proposal features 3 Work Packages (WP) of progressively more challenging character. In WP1, the palladium(0)-catalyzed ligand-controlled regioconvergent coupling of organozinc compounds, obtained from mixtures of alkyl bromides, is proposed. Coupling this migrative cross-coupling with an initial C-H bromination step would allow to selectively functionalize alkanes in two-steps at the terminal carbon. WP2 features the development of a nickel-catalyzed version of the preceding migrative coupling, which would offer a useful complementarity both in terms of scope and mechanism. The main purpose of WP3 is to replace organozinc reagents employed in the Ni-catalyzed process (WP2) with photoredox-generated radicals, such as those generated from carboxylic acids or amines in combination with an Ir-based photocatalyst. This modification would allow to significantly expand the scope and practicability of this C-H functionalization strategy.

The goal of this proposal is to develop a new strategy for asymmetric C(sp3)−H activation using a chiral base instead of chiral ligand, and will focus on oxidative addition-induced and decarboxylation-induced reactions. Using this new strategy, a wide range of representative and valuable chiral four-membered (hetero)cyclic and five-membered (hetero)cyclic organic molecules will be synthesized. Typical chiral Br¢nsted acids and the designed ionic liquid-functionalized chiral phosphoric acids will be prepared by using commercially available raw materials. They will be tested in the two proposed concepts. In the case of oxidative addition-induced reactions, some feasible examples aiming at synthesizing chiral indanes, indolines, dihydrobenzofurans, benzocyclobutenes, and lactams will be developed from readily available aryl or alkenyl halides or triflates. For the decarboxylation-induced reactions, a racemic version will be first developed. Then, the chiral base concept will be applied in the synthesis of chiral benzocyclobutenes, indanes, indolines, and dihydrobenzofurans. In each of the reactions involved, some key reaction parameters including chiral acid, ligand, solvent, base, reaction temperature as well as the structural features of the substrates will be studied. In addition, recyclable ionic liquid-functionalized chiral Br¢nsted acids and the effect of traditional ionic liquids as the additives or solvents will be first studied in enantioselective C(sp3)−H bond activation. In order to get a clear understanding on the nature of the asymmetric induction during the catalytic cycle, computational studies will also be performed using DFT methods. The applicant's previous research experience in C−H activation, ionic liquids catalysis and asymmetric catalysis areas will benefit the project. The project will foster mutually beneficial research collaboration in Europe in the field of C−H activation and green chemistry.