Identificador: TDX:2418
Autors: La Cascia, Enrico
Resum:
The first part covered the topic of the β-boration reaction towards the synthesis of γ-amino alcohols. A new metal-free approach to the β-borylation of α,β-unsaturated imines generated in situ has been reported. In this case the diboron compound, bis(pinacolato)diboron, is activated by a base/MeOH system which generates a nucleophilic boron moiety that can interact with a α,β-unsaturated acceptor (imine). This latter is activated by a catalytic amount of phosphine.
When a chiral phosphine such as (S)-MeBoPhoz is used, the β-borylation can be performed in an enantioselective manner with ee values up to 70%.
After a high diasteroselective protocol of reduction and oxidation we could provide the desired γ-amino alcohol.
Interestingly, when a copper salt is modified with the (S)-MeBoPhoz ligand the enantioselectivities dropped showing generally lower values of ee than the organocatalytic approach.
It has been tried to apply this chemistry to the synthesis of bioactive compounds such as Tramadol
This part of the manuscript covered the attempts that were made to achieve the total synthesis. Many catalytic systems have been tried but unfortunately, none of them had positive results.
The last part of the thesis is based on the insertion of a diazocompound, such as (trimethylsilyl)diazomethane), to generate the gem-diboron compound 18.
The treatment of compound 18 with a lithiated base, such as LiTMP, generated a stabilized carbanion which can attack carbonyl compounds like ketones to afford, after a Peterson-type B-O elimination, a gem-silylboron olefin.
We demonstrated that further functionalizations, suck as Suzuki-Miyaura cross-coupling, could be performed.
Even the more challenging iododesilylation was successfully allowing the synthesis of tetrasubstituted olefins after two consecutive cross-couplings.
Towards this aim, the synthesis of (E)-Tamoxifen was achieved with high values of selectivity (ratio E/Z = 90:10).
Repositori URV