Asymmetric metal-catalyzed [3+2] cycloadditions of azomethine ylides

Stohler, Remo. Asymmetric metal-catalyzed [3+2] cycloadditions of azomethine ylides. 2006, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_7907

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Cycloadditions of azomethine ylides with olefins provide a short, attractive route to pyrrolidine units with the
potential to control the relative and absolute configuration by means of a chiral catalyst. Grigg and co-workers
have pioneered the use of chiral transition metal complexes to induce enantioselective cycloadditions of this
type. However, stoichiometric amounts of metal complexes were employed in this work.
Paying regard to Griggs investigations it was intended to develop a system which gives asymmetric induction
using catalytic amounts of chiral transition metal complexes. A first screening of different transition metal
sources showed promising results for Cu(I) and Ag(I) species. The application of their complexes with several
members of different ligand classes to the 1,3-dipolar cycloaddition reaction directed the interest towards
phosphinooxazoline (PHOX) ligands. The catalysts derived from the two different metals and PHOX ligand 39
induced enantioselectivity in both cases. Subsequent investigations demonstrated that
also the use of the analogous Au(I) catalyst led to the formation of enantioenriched pyrrolidines.
Although the Cu(I)-PHOX catalyst generated the five-membered heterocycle 38a with higher enantiomeric
excess than the other two catalysts (Table 28, compare entries 1 with 2 and 3) the focus was directed to the
Ag(I) system. Firstly, because a further screening with differently substituted PHOX ligands indicated only for
the Ag(I) system the chance of substantial improvement of the enantioselectivity. Secondly, much higher
endo:exo selectivity could be observed than for the other two systems. Optimization of the substitution pattern of
the PHOX ligand showed that particularly the variation of the substituents at the phosphorous atom
and the C5 position of the oxazoline moiety had a positive effect on asymmetric induction.
Scheme 47 shows the most selective PHOX ligand (79) found to date which resulted in formation of the
pyrrolidine product 38a with 84% enantiomeric excess.
Although Ag(I)-PHOX complexes gave only moderate to good asymmetric induction in intermolecular
[3+2] cycloadditions, they demonstrated to be efficient catalysts for intramolecular [3+2] cycloadditions of
azomethine ylides, giving access to tricylic products with almost complete diastereocontrol and enantiomeric
excesses of up to 99%..
Additionally the C5-substituted PHOX ligands, originally synthesized for the [3+2] cycloaddition reaction, were
applied to the Ir(I)-catalyzed asymmetric hydrogenation of an imine as well as tri- and tetrasubstituted olefins.
They induced similar or superior enantioselectivity than the best PHOX ligand (bis(ortho-tolyl)phosphino-tertbutyloxazoline).
This confirmed the preliminary assumption that the steric bulk caused by the substituents at the
C5 position of the oxazoline ring might direct the methyl groups of the isopropyl substituent at the C4 position to
the coordination center creating a “tertiary butyl substitute“. Thus, this ligand type represents a less expensive
substitute of the tert-leucine-derived PHOX ligand.
Advisors:Pfaltz, Andreas
Committee Members:Woggon, Wolf-Dietrich
Faculties and Departments:05 Faculty of Science > Departement Chemie > Former Organization Units Chemistry > Synthetische organische Chemie (Pfaltz)
UniBasel Contributors:Pfaltz, Andreas and Woggon, Wolf-Dietrich
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:7907
Thesis status:Complete
Number of Pages:241
Identification Number:
edoc DOI:
Last Modified:05 Apr 2018 17:32
Deposited On:13 Feb 2009 16:04

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