Identificador: TDX:869
Autores: Ramírez Artero, Jesús
Resumen:
Organoboron compounds are very useful intermediates in organicsynthesis, because the carbon-boron bond can be cleaved in a variety of ways leading to the formation of useful functional groups. The catalyzed diboration ofalkenes and alkynes has been widely studied in the last 15 years, obtaining high yields and activities in the alkyne catalyzed diboration reaction. However, when alkenes are used as substrates in the catalyzed diboration reaction, the problem of b-hydride elimination could arise, preventing a good agreement between catalytic activity and chemoselectivity. <br>In the first chapter of this thesys an overview of the precedents of the diboration reactions of alkenes and alkynes is presented, including the different metals and ligands used in this reactions and the mechanistic studies published to date. Moreover, there has been collected the different derivatizations of organoboron intermediates carried out. The microwave technique is also described briefly. Finally, the scope of this thesys is explained, including the development of new catalytic systems which improve the activity, chemoselectivity and enantioselectivity of the catalytic systems previously reported, the study of the mechanism of the rhodium catalyzed alkene diboration reaction, and the search of new routes for the fluorofunctionalization of organoboron compounds. <br>In the second chapter, the activity, chemoselectivity and enantioselectivity of different catalytic precursors in the alkene and alkyne catalytic diboration reaction is described. In the first part, a deep study on the rhodium catalyzed alkene diboration reaction is carried out, finding in this case that the steric effects on the diborating reagent have a dramatic effect on the chemoselectivity of the reaction. It is also observed that the DPPM (bis(diphenylphosphino)methane) is the ligand which provide a better chemoselectivity, showing an important bite angle influence on the ligand, while QUINAP (1-(2-diphenilphosphino-1-naphthyl)isoquinoline) is the ligand which offers a higher enantioselectivity. In the next parts it is described the utilization of different gold, silver, copper and platinum complexes as catalyst precursors, which improve the chemoselectivity of the reaction, reducing the b-hydride elimination side reaction. Despite several chiral carbene modified complexes have been used, only in one case some enantioselectivity was induced, using a carbene modified copper complex, but reducing chemoselectivity. It is also described the application of arbene modified copper and platinum complexes as catalyst precursors in the alkyne diboration reaction, obtaining good results in activity and chemoselectivity. The utilization of new reaction conditions, in which an excess of the diborating reagent (2 eq.) and the addition of a base (NaOAc) is required, improve the activity of catalytic systems like BINAP 2,2’-bis(difenilfosfino)-1,1’-binaphthyl) modified gold complexes, whose activity was very low under the typical conditions; unfortunately, no enantioselectivity was obtained in this case. Finally, it is described the application of microwave techniques to the platinum catalyzed alkyne diboration reaction, in order to reduce the reaction times.In the third chapter, an in-depth study of the mechanism of the Rh(I)-catalyzed alkene diboration reaction is described. First of all, an NMR (Nuclear Magnetic Ressonance) study was carried out in order to identify plausible intermediates. Next, a DFT (Density Functional Theory) study of the reaction mechanism was carried out, finding that after the oxidative addition of the diborane, an insertion of the alkene into a Rh-B bond is produced, followed by an internal rearrangement in order to ocupy the vacant position created, and,finally, reductive elimination of the product is produced, being the most favourable path that in which the alkene is placed trans to the nitrogen of the QUINAP ligand. The study of the b-hydride elimination side reaction shows that the utilization of BINAP as ligand favours it, with respect to the utilization of QUINAP. <br>In the fourth chapter, the fluorofunctionalization of cis-1,2-bis(boryl)alkenes is described, leading to the formation of a,a-difluorinated ketones through an eletrophilic fluorination process. First of all, a little introduction to the electrophilic fluorination processes is made, with special interest to the electrophilic fluorination of organosilanes, which are quite similar to the organoboron compounds. The reaction is carried out starting from alkynes, through a tandem catalytic diboration/electrophilic fluorination process process. Only the cis-1,2-bis(boryl)alkenes derived from bis(pinacolato)diboron are susceptible to the fluorination process. Internal alkynes are more reactive than terminal ones. It is also described the synthesis of a,a-difluoroimines directly from alkynes through a tandem catalytic diboration/electrophilic fluorination/imination process, the efficiency of which depends on the electronic properties of the substrate.<br>Finally, in the fifth chapter, the asymmetric electrophilic fluorination of a-nitro esters is described. This process was carried out using cinchona derivatives chiral auxiliaries, obtaining enantiomeric excesses up to 40%.
Repositori URV