DOI: 10.1002/anie.201103683
Organocatalysis
Generation of a,b-Unsaturated Iminium Ions by Laser Flash
Photolysis**
Sami Lakhdar,* Johannes Ammer, and Herbert Mayr*
Dedicated to Professor Gerhard Bringmann on the occasion of his 60th birthday
Iminium activation has become one of the most important
methods in enantioselective synthesis.[1] For the optimization
and the rational design of organocatalytic cycles, knowledge
of the mechanism of these reactions is crucial.[2] In previous
work, we have shown that the rate constants for the reactions
of unsaturated iminium ions with ketene acetals,[2d] sulfur
ylides,[3] and pyrroles[4] can be determined by UV/Vis
spectroscopy employing conventional spectrometers or
stopped-flow equipment. Both methods require the mixing
of the reactants, and therefore are not applicable to reactions
that proceed on the sub-millisecond time scale.
We now report on the in situ laser-flash-photolytic
generation of iminium ions derived from cinnamaldehyde
Scheme 1.
and imidazolidinones, which allowed us to measure rate
constants for the reactions of iminium ions with strong
nucleophiles. This method along with previously reported
kinetic procedures have been employed to directly compare
the electrophilic reactivities of iminium ions derived from
different imidazolidinones.
Treatment of the imidazolidinonium salts 1a–c with
cinnamaldehyde (2) in methanol or ethanol following liter-
ature procedures[5,6] gave precipitates of the iminium salts 3a–
c (Scheme 1), which were previously analyzed by X-ray
crystallography.[5a,6c] When these crystals were dissolved in
acetonitrile, only the E isomers of 3a–c were observed by
NMR spectroscopy.[7]
Combination of the iminium salts 3a–c with one equiv-
alent of tributylphosphine gave the (E)-enaminophospho-
nium salts 4a–c as mixtures of two diastereoisomers (2:1 for
4a and 4c and 1:1 for 4b; Scheme 1). Selective formation of
the (E)-enamines 5a–c (1:1 ratio of two diastereoisomers)
was observed when solutions of 3a–c in acetonitrile were
treated with excess piperidine (Scheme 1).[8]
As organocatalytic processes involving 3a–c are often
highly enantioselective,[9] we have to conclude that the low
stereoselectivities of the stoichiometric reactions with PBu3
and piperidine in Scheme 1 are due to reversible reactions
under the conditions employed.
Tri-n-butylphosphine has previously been reported to be
an effective photo-leaving group for the laser-flash-photolytic
generation of stabilized carbocations.[10] Irradiation of aceto-
nitrile solutions of the phosphonium salts 4a–c with 7 ns laser
pulses from the fourth harmonic of a Nd/YAG laser (266 nm,
30–60 mJpulseꢀ1) yielded the iminium ions 3a–c which
showed the same UV/Vis absorption maxima lmax as solutions
of the isolated iminium salts in acetonitrile (Figure 1a).
When salts 3a–c were generated in the presence of a large
excess of the nucleophiles 6j or 6l–o, we observed mono-
exponentional decays of their absorbances, from which the
rate constants kobs (sꢀ1) were obtained (Figure 1b). Plots of
kobs versus the nucleophile concentrations were linear (Fig-
ure 1c) and provided the second-order rate constants k2
(mꢀ1 sꢀ1) which are listed in Table 1.
In order to provide a broader experimental basis for the
comparison of the electrophilicities of iminium ions derived
from different imidazolidinones we have also determined rate
constants of the reactions of 3a, 3b, and 3c with weaker
nucleophiles using convential UV spectrometers and
stopped-flow techniques. The rate of the reaction of 3a with
DBU (6l) has been determined in two ways, with laser-flash-
photolytically generated iminium ions as well as with
solutions of isolated iminium salts, and the values differed
by less than 6%. This agreement is remarkable in view of
Seebachꢀs hypothesis that (E)-iminium ions are more reactive
than their Z isomers.[6e] As we do not know the configuration
of the photolytically generated iminium ions, the monoexpo-
[*] Dr. S. Lakhdar, Dipl.-Ing. J. Ammer, Prof. Dr. H. Mayr
Department Chemie, Ludwig-Maximilians-Universitꢀt Mꢁnchen
Butenandtstrasse 5–13 (Haus F), 81377 Mꢁnchen (Germany)
E-mail: sami.lakhdar@cup.uni-muenchen.de
[**] We thank the Alexander von Humboldt Foundation (research
fellowship for S.L.) and the Deutsche Forschungsgemeinschaft (Ma
673/21-3) for support of this work, Dr. P. Mayer for the X-ray
structure determination, Prof. S. Kobayashi for installing the laser
flash photolysis working station, and Dr. A. R. Ofial and Prof. D.
Seebach for helpful comments.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2011, 50, 9953 –9956
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
9953