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Digital archive of theses discussed at the University of Pisa


Thesis etd-01282010-120423

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