Download DESIGN OF CHIRAL IMINO- AND AMINOPYRIDINE LIGANDS

DESIGN OF CHIRAL IMINO- AND AMINOPYRIDINE LIGANDS.
APPLICATION TO THE ENANTIOSELECTIVE HENRY REACTION
Doctoral Thesis by Victor Hernández Olmos
The synthesis of new molecules that can work as chiral ligands in metal catalyzed
enantioselective reactions is currently an area of great interest.1,2 These ligands must
be capable of coordinating with the metal ion, generating around it a highly
asymmetric environment so that the complex formed is capable of promoting the
reaction with good yield and high enantioselectivity. It is also important that the
ligands are easily obtained from accessible starting materials and can be prepared in
both enantiomeric forms.
According to these considerations as the first objective of this thesis were
designed and synthesized new imino- and aminopyridine ligands for asymmetric
catalysis based on the design showed in the figure.
On the other hand, reactions allowing the formation of C-C bonds are of great
importance in organic synthesis because they allow to increase the structural
complexity of the molecules. Among such reactions, the Henry or nitroaldol reaction 3
constitutes one of the most useful methodologies for the formation of C-C bonds.
During the reaction, at least one stereogenic center is also generated. Due to the
chemical versatility of the hydroxyl and nitro groups, the resulting βhydroxynitroalkanes are valuable intermediates for the synthesis of a variety of
functionalized molecules and biologically active compounds. Consequently, in recent
years, considerable effort towards the development of catalytic and asymmetric
versions of this reaction has been devoted.4
The second objective of the thesis has been the application of the ligands
prepared in reactions of addition of nitroalkanes to various carbonyl substrates
catalyzed by metal ions.
1. Lewis Acids in Organic Synthesis; Yamamoto, H., Ed.; Wiley-VCH: Weinheim, 2000.
2. Bolm, C.; Gladysz, J. Chem. Rev. 2003, 103, 2761-2762.
3. Henry, L. Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences 1895,
120, 1265-1268.
4. a) Luzzio, F. A. Tetrahedron 2001, 57, 915-945. b) Palomo, C.; Oiarbide, M.; Mielgo, A.
Angew. Chem. Int. Ed. 2004, 43, 5442-5444. c) Boruwa, J.; Gogoi, N.; Saikia, P. P.; Barua, N.
C. Tetrahedron: Asymmetry 2007, 17, 3315-3326. d) Palomo, C.; Oiarbide, M.; Laso, A. Eur. J.
Org. Chem. 2007, 2561-2574. e) Marques-Lopez, E.; Merino, P.; Tejero, T.; Herrera, R. P. Eur.
J. Org. Chem. 2009, 2401-2420.