STRUCTURAL EFFECTS FOR THE IMPROVEMENT OF SYNTHETIC METHODS

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Structural effects for the improvement of synthetic methods

Publication . Martins, Nelson C.; Fernandes, A.; Xiao, Jianliang

The demand for enantiopure compounds in society motivates chemists to develop methods for asymmetric synthesis. Asymmetric catalysis is central in this context, its development significantly depending on the discovery of new successful chiral ligands. Ferrocenes represent powerful and unique chiral ligands which may contain a chiral plane. Such chirality is often built in the ferrocene backbone via diastereoselective ortho-lithiation and functionalization of monosubstituted ferrocenes containing a chiral ortho-directing group (CDG). Accordingly the oxazaphospholidine oxide group has been studied allowing highly stereoselective synthesis of planar chiral 1,2-disubstituted ferrocenes. Herein we expand on the exploration of this interesting group aiming to further access on its potential for the synthesis of useful chiral ferrocenyl phosphines to be applied in catalysis. Thus observation of two P-epimers during the formation of the starting ferrocenyl oxazaphospholidine oxide led to the synthesis of novel ligands, including diastereopure 1,2-disubstituted ferrocenes with opposite planar chirality, as shown below. Additional investigation included a second lithiation step at the 1,2-disubstituted ferrocenes, preparation of P-chiral ligands based on stereoselective induction by the oxazaphospholidine oxide, and its reduction, all together leading to new structures. Coordination chemistry and catalysis involving our ligands were approached revealing oxazaphospholidine oxide group ability to act as a hemilabile ligand coordinating to palladium at the phosphoryl oxygen. The ligands displayed potential activity, both on the Suzuki-Miyaura cross-coupling and Asymmetric Allylic Alkylation, this last case involving moderate enantioselectivities, up to 70 % ee. Finally the possibility to use phenolic benzisothiazolyl and tetrazolyl ethers in Suzuki-Miyaura reaction was evaluated revealing positive results, with the tetrazolyl ones.

2012Doctoral thesis

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