Ferrocene-Based Chiral Catalyst Design for Enantioselective Cycloadditions Reactions

For the the last two decades homogenous gold(I) catalysis emerged as a powerful synthetic tools and cycloisomerizations of 1,n-enynes are among the most recognized gold(I)-catalyzed transformations. Despite the “Gold Rush” that has seen a fast development of gold(I)-catalyzed transformations, the development of enantioselective gold(I) catalysis proceeded at a slower rate. This thesis describes the design and synthesis of a new class of ferrocene-based ligands applied to enantioselective gold(I) catalysis. These ligands have been specifically implemented to overcome difficulties of enantioselective gold(I) catalysis due to the spatial separation between the chiral information on the ligand and the catalytic site located on the opposite side of the metal center. A modular synthesis of 1-(2’-dialkylarylphosphine)-3-arylferrocene was developed allowing to access a family of chiral gold(I) complexes bearing various steric and electronic properties. One chiral gold(I) complex was identified to catalyze the formal [4+2] cycloaddition of 1,6-arylenynes in high yields and good enantioselectivities. The working mode of our chiral catalysts was studied computationally. An attractive non-covalent interaction between the ligand and the substrate was found to be crucial to achieve high enantioinduction.

Additionally, we applied a phosphine-supported gold(I) complex containing a chiral remote C2-symmetric 2,5-disubstituted pyrrolidines to the enantioselective synthesis of planar chiral ferrocenes by hydroarylation of (2-alkynylaryl)ferrocenes.

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