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Tesi etd-01282010-120423

Thesis type
Tesi di dottorato di ricerca
Deoxycholic derived biphenylphosphites: a new class of tropos ligands for asymmetric catalysis
Settore scientifico disciplinare
Corso di studi
tutor Prof. Iuliano, Anna
Parole chiave
  • catalisi asimmetrica; acidi biliari; tropos
Data inizio appello
Data di rilascio
Riassunto analitico
This PhD thesis deals with synthesis, characterization and application as chiral<br>inducers in asymmetric catalysis of a new class of tropos ligands derived from de-<br>oxycholic acid.<br>Following the longstanding interest of our research group in the use of bile acid<br>derivatives in enantioselective processes, attention was addressed to the develop-<br>ment of tropos biphenylphosphite ligands. Taking advance of the asymmetric ac-<br>tivation approach, which proved to be successful for the development of different<br>chiral auxiliaries for asymmetric synthesis (Chapter 1), the steroidal backbone of<br>the deoxycholic acid was used as chiral activator in order to have a diastereomeric<br>control and to induce a prevalent screw sense on the tropos biarylphosphite moieties.<br>A family of seven deoxycholic derived biphenylphosphite ligands (Figure 1) was<br>synthesized and stereochemically characterized by means of NMR and Circular<br>Dichroism spectroscopies (Chapter 2), which demonstrated the tropos nature of<br>the ligands along with the capability of the bile acid to induce a prevalent screw<br>sense on the biphenylphosphite moieties. Moreover, the sense and the extent of this<br>prevalence were determined, as well as the peculiar dependence of the sense of twist<br>of the biphenyl moiety on the solvent: in Chapter 2, in fact, it is also showed that<br>the M-P equilibrium, in the majority of the phosphites is shifted towards the M<br>form in ACN and towards the P form in THF.<br>This new family of ligands was first tested in the copper(I)-asymmetric conjugate<br>addition of diethylzinc to enones (Chapter 3), affording the alkylation products with<br>ees up to 65%. The extent of the enantioselectivity depended on the substitution on<br>the biphenyl moiety of the phosphite, whereas the sense of the asymmetric induction<br>depended on the reaction solvent. In fact, performing the reaction in toluene, where<br>the biphenyl moiety of the phosphites 1-5 has M prevalent screw sense afforded the<br>S-configured alkylation product, whereas using THF, where P sense of twist prevails,<br>the R alkylation product was obtained.<br>Biphenylphosphite ligands 1-6 were also applied in rhodium catalyzed reactions<br>(Chapters 4-6). The Rh catalyzed asymmetric hydrogenation was first investigated,<br>31<br>in which very high values of asymmetric inductions were obtained. P-NMR and CD<br>measurements on the rhodium complexes of some phosphites were also performed,<br>allowing to shed light on nature and stereochemical features of the catalytic species<br>as well as on the asymmetric induction process (Chapter 4).<br>The study performed on the asymmetric addition of arylboronic acids to cyclic<br>enones underlined the effectiveness of phosphites 1-6 as chiral ligands in rhodium<br>catalyzed reactions: also in this case very high activities and enantioselectivities<br>were observed. These ligands also showed a unique behavior, being able to afford<br>mono or disubstituted Rh(I) complexes, depending on the P:Rh ratio used and the<br>reaction time, both showing catalytic activity and enantioselectivity. The compari-<br>son with the corresponding atropoisomeric analogues phosphites permitted to gain<br>important information about the stereochemical outcome of the reaction. In ad-<br>dition, the use of disubstituted complexes led to the formation of double addition<br>products 1,3-diarylcyclohexanols, obtained with complete diastereoselectivity and<br>ees up to 94% (Chapter 5).<br>Taking into account the rare use of monodentate ligands in asymmetric hydro-<br>formylation reactions, biphenylphosphites 1-6 were assayed also in this reaction: the<br>task proved to be not a trivial one, since enantioselectivity without using a chelating<br>ligand was often elusive, but nevertheless promising results for further investigations<br>were obtained using ligand 5 (Chapter 6).<br>