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Digital archive of theses discussed at the University of Pisa


Thesis etd-01172013-154821

Thesis type
Tesi di dottorato di ricerca
Thesis title
Academic discipline
Course of study
tutor Prof. Iuliano, Anna
  • asymmetric catalysis
  • bile acid
  • chiral biaryls
  • diarylcarbinols
  • monophosphite ligands
  • nitroalkanes
Graduation session start date
The research presented herein is concerned with the application of already known both atropoisomeric and flexible monodentate phosphites derived from bile acids in rhodium as well as palladium catalyzed asymmetric transformations. Attention has been devoted also towards the synthesis and the stereochemical characterization of new flexible phosphites derived from bile acids and their evaluation as chiral ligands in the Rh-catalyzed asymmetric hydrogenation.
Chapter 1 of this thesis is a survey of different monodentate phosphorus ligands, their structures, synthesis and application in asymmetric catalysis and focuses on the usefulness of monodentate ligands with respect the bidentate ones. This Chapter also outlines the aims of this project, which were to explore usability and generality of bile acid derived monophosphite ligands in the asymmetric reactions described in Chapters 2-4, as well as to develop new bile acid derived flexible binaphthyl phosphites.
The use of biaryl phosphites derived from deoxycholic acid as chiral ligands in the Pd-catalyzed asymmetric Suzuki–Miyaura cross-coupling of arylboronic acids with aryl bromides is presented in Chapter 2, after a short general discussion on the reaction. The first part of the work is focused on the study of the different reaction parameters, from which the role of the base emerges as being crucial for the outcome of the reaction. Afterwards, an accurate study on thea L:Pd ratio is also reported, which gets some light on the nature of the catalytically active species involved in the reaction. Finally the general applicability of the reaction is reported by presenting the results obtained in the asymmetric coupling of different aryl halides and arylboronic acids.
Chapter 3 concerns the use of deoxycholic acid derived tropos and atropoisomeric phosphites as chiral ligands in the Rh-catalyzed enantioselective addition of arylboronic acids to arylaldehydes and 2,2,2-trifluoroacetophenone. A brief introduction on the literature examples of this reaction precedes the discussion of the work. In this chapter a new bile acid derived phosphite ligand is reported, which has stereochemical characteristics in between the atropoisomeric and flexible phosphites, useful to shed light on the different behavior of flexible and atropoisomeric ligands in the reaction. The results obtained using the different phosphites are discussed, showing the best performances of the Rh-complex obtained starting from one of the two atropoisomeric ligands, which afforded complete conversion of the carbonyl compounds in short reaction times under mild reaction conditions and with ee’s of up to 84%. A kinetic study of the reactions promoted by the diastereomeric atropoisomeric ligands aimed at explaining the outcome of the reaction is also reported.
Chapter 4 reports on the results obtained in the Rh-catalyzed asymmetric conjugate addition of arylboronic acids to nitroalkenes. A short introduction is dedicated to the literature examples of this reaction, as well as to the importance and usefulness of the optically active nitroalkanes. After discussing the optimization of the reaction condition of the conjugate addition of phenylboronic to 1-nitrocyclohexene in the presence of a representative ligand, the results obtained in the same reaction using the other phospites are shown, focusing the attention on the structural and stereochemical characteristics that makes the ligand efficient. The final part of the chapter shows the applicability of the best performing catalytic system to different nitrostyrenes and arylboronic acids and the discussion of the results.
Chapter 5 describes the synthesis of three new bile acid derived “tropos vaulted phosphites” and their stereochemical characterisation by CD and NMR spectroscopies. The spectroscopic investigation is mainly devoted to ascertain the capability of the cholestanic backbone of bile acids to induce a prevalent screw sense on the flexible 2,2’-binaphthylphosphite moiety linked at the three different hydroxylated positions of bile acids, to determine the sense of twist and its extent, in dependence on the position where the flexible moiety is linked on the steroidal skeleton. The use of the three phosphites as chiral ligands in the Rh-catalyzed asymmetric hydrogenation is reported, together with an NMR characterization of Rh-complexes.